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Maintaining precise synaptic contacts between neuronal partners is critical to ensure the proper functioning of the mammalian central nervous system (CNS). Diverse cell recognition molecules, such as classic cadherins (Cdhs), are part of the molecular machinery mediating synaptic choices during development and synaptic maintenance. Yet, the principles governing neuron-neuron wiring across diverse CNS neuron types remain largely unknown. The retinotectal synapses, connections from the retinal ganglion cells (RGCs) to the superior collicular (SC) neurons, offer an ideal experimental system to reveal molecular logic underlying synaptic choices and formation. This is due to the retina's unidirectional and laminar-restricted projections to the SC and the large databases of presynaptic RGC subtypes and postsynaptic SC neuronal types. Here, we focused on determining the role of Type II Cdhs in wiring the retinotectal synapses. We surveyed Cdhs expression patterns at neuronal resolution and revealed that Cdh13 is enriched in the wide-field neurons in the superficial SC (sSC). In either the Cdh13 null mutant or selective adult deletion within the wide-field neurons, there is a significant reduction of spine densities in the distal dendrites of these neurons in both sexes. Additionally, Cdh13 removal from presynaptic RGCs reduced dendritic spines in the postsynaptic wide-field neurons. Cdh13-expressing RGCs use differential mechanisms than αRGCs and On-Off Direction-Selective Ganglion Cells (ooDSGCs) to form specific retinotectal synapses. The results revealed a selective transneuronal interaction mediated by Cdh13 to maintain proper retinotectal synapses in vivo.

Barn owls enable investigation of neural mechanisms underlying stimulus selection of concurrent stimuli. The audiovisual space map in the optic tectum (OT), avian homolog of the superior colliculus, encodes relative strength of concurrent auditory stimuli through spike response rate and interneuronal spike train synchrony (STS). Open questions remain regarding stimulus selection in downstream forebrain regions lacking topographic coding of auditory space, including the functional consequences of interneuronal STS on interregional signaling. To this end, we presented concurrent stimuli at different locations and manipulated relative strength while simultaneously recording neural responses from OT and its downstream thalamic target, nucleus rotundus (nRt), in awake barn owls of both sexes. Results demonstrated that broadly spatially tuned nRt units exhibit different spike response patterns to competition depending on spatial tuning preferences. Modeling suggests nRt units integrate convergent inputs from distant locations across midbrain map regions. Additionally, STS within nRt reflects the temporal properties of the strongest stimulus. Furthermore, interregional STS between OT and nRt was strongest when spatial tuning overlap between units across regions was large and when the strongest stimulus location during competition was favorable for units in both regions. Additionally, though gamma oscillations synthesized within OT are weakly propagated within nRt, average gamma power across regions correlates with strength of interregional STS. Overall, we demonstrate that nRt integrates inputs across distant areas of OT, retains spatial information through differences in strength of inputs from various locations of the midbrain map across neurons, and prioritizes coding of identity features to the strongest sound. [ABSTRACT FROM AUTHOR]

The looming stimulus-evoked flight response to approaching predators is a defensive behavior in most animals. However, how looming stimuli are detected in the retina and transmitted to the brain remains unclear. Here, we report that a group of GABAergic retinal ganglion cells (RGCs) projecting to the superior colliculus (SC) transmit looming signals from the retina to the brain, mediating the looming-evoked flight behavior by releasing GABA. GAD2-Cre and vGAT-Cre transgenic mice were used in combination with Cre-activated anterograde or retrograde tracer viruses to map the inputs to specific GABAergic RGC circuits. Optogenetic technology was used to assess the function of SC-projecting GABAergic RGCs (scpgRGCs) in the SC. FDIO-DTA (Flp-dependent Double-Floxed Inverted Open reading frame-Diphtheria toxin) combined with the FLP (Florfenicol, Lincomycin & Prednisolone) approach was used to ablate or silence scpgRGCs. In the mouse retina, GABAergic RGCs project to different brain areas, including the SC. ScpgRGCs are monosynaptically connected to parvalbumin-positive SC neurons known to be required for the looming-evoked flight response. Optogenetic activation of scpgRGCs triggers GABA-mediated inhibition in SC neurons. Ablation or silencing of scpgRGCs compromises looming-evoked flight responses without affecting image-forming functions. Our study reveals that scpgRGCs control the looming-evoked flight response by regulating SC neurons via GABA, providing novel insight into the regulation of innate defensive behaviors. [ABSTRACT FROM AUTHOR]

With the rapid development of sensors and sensor technology, facial expression recognition (FER) systems can be developed and applied to real-world scenarios. Vision scan sensors and ambient light sensors capture clear and noise-free images of faces. However, in the real world, annotating large facial expressions is challenging owing to inconsistent labels, which are caused by the annotators' subjectivity and the facial expressions' ambiguity. Moreover, current studies present limitations when addressing facial expression differences due to the gender gap. We not only rely on visual sensors for FER but also utilize nonvisual sensors. Therefore, in this paper, we propose a self-cure dual-branch network (SC-DBN) for FER, which automatically prevents deep networks from overfitting ambiguous samples. First, on the basis of SC-DBN, a two-branch training method is designed, taking full advantage of the gender information. Furthermore, a self-attention mechanism highlights the essential samples and weights, each with a regular weighting. Finally, a relabeling module is used to modify the labels of these samples in inconsistent labels. Many experiments on public datasets show that SC-DBN can effectively integrate gendered information and self-cure networks to improve performance. [ABSTRACT FROM AUTHOR]

A unique population of ventral tegmental area (VTA) neurons co-transmits glutamate and GABA. However, the circuit inputs to VTA VGluT2+VGaT+ neurons are unknown, limiting our understanding of their functional capabilities. By coupling monosynaptic rabies tracing with intersectional genetic targeting in male and female mice, we found that VTA VGluT2+VGaT+ neurons received diverse brainwide inputs. The largest numbers of monosynaptic inputs to VTA VGluT2+VGaT+ neurons were from superior colliculus (SC), lateral hypothalamus (LH), midbrain reticular nucleus, and periaqueductal gray, whereas the densest inputs relative to brain region volume were from the dorsal raphe nucleus, lateral habenula, and VTA. Based on these and prior data, we hypothesized that LH and SC inputs were from glutamatergic neurons. Optical activation of glutamatergic LH neurons activated VTA VGluT2 +VGaT+ neurons regardless of stimulation frequency and resulted in flee-like ambulatory behavior. In contrast, optical activation of glutamatergic SC neurons activated VTA VGluT2+VGaT+ neurons for a brief period of time at high frequency and resulted in head rotation and arrested ambulatory behavior (freezing). Stimulation of glutamatergic LH neurons, but not glutamatergic SC neurons, was associated with VTA VGluT2+VGaT+ footshock-induced activity and inhibition of LH glutamatergic neurons disrupted VTA VGluT2+VGaT+ tailshock-induced activity. We interpret these results such that inputs to VTA VGluT2+VGaT+ neurons may integrate diverse signals related to the detection and processing of motivationally salient outcomes. [ABSTRACT FROM AUTHOR]

The sudden appearance of a visual distractor shortly before saccade initiation can capture spatial attention and modulate the saccade trajectory in spite of the ongoing execution of the initial plan to shift gaze straight to the saccade target. To elucidate the neural correlates underlying these curved saccades, we recorded from single neurons in the frontal eye field of two male rhesus monkeys shifting gaze to a target while a distractor with the same eccentricity appeared either left or right of the target at various delays after target presentation. We found that the population level of presaccadic activity of neurons representing the distractor location encoded the direction of the saccade trajectory. Stronger activity occurred when saccades curved toward the distractor, and weaker when saccades curved away. This relationship held whether the distractor was ipsilateral or contralateral to the recorded neurons. Meanwhile, visually responsive neurons showed asymmetrical patterns of excitatory responses that varied with the location of the distractor and the duration of distractor processing relating to attentional capture and distractor inhibition. During earlier distractor processing, neurons encoded curvature toward the distractor. During later distractor processing, neurons encoded curvature away from the distractor. This was observed when saccades curved away from distractors contralateral to the recording site and when saccades curved toward distractors ipsilateral to the recording site. These findings indicate that saccadic motor planning involves dynamic push--pull hemispheric interactions producing attraction or repulsion for potential but unselected saccade targets. [ABSTRACT FROM AUTHOR]

Saccade accommodation is a productive model for exploring the role of the cerebellum in behavioral plasticity. In this model, the target is moved during the saccade, gradually inducing a change in the saccade vector as the animal adapts. The climbing fiber pathway from the inferior olive provides a visual error signal generated by the superior colliculus that is believed to be crucial for cerebellar adaptation. However, the primate tecto-olivary pathway has only been explored using large injections of the central portion of the superior colliculus. To provide a more detailed picture, we have made injections of anterograde tracers into various regions of the macaque superior colliculus. As shown previously, large central injections primarily label a dense terminal field within the C subdivision at caudal end of the contralateral medial inferior olive. Several, previously unobserved, sites of sparse terminal labeling were noted: bilaterally in the dorsal cap of Kooy and ipsilaterally in the C subdivision of the medial inferior olive. Small, physiologically directed, injections into the rostral, small saccade portion of the superior colliculus produced terminal fields in the same regions of the medial inferior olive, but with decreased density. Small injections of the caudal superior colliculus, where large amplitude gaze changes are encoded, again labeled a terminal field located in the same areas. The lack of a topographic pattern within the main tecto-olivary projection suggests that either the precise vector of the visual error is not transmitted to the vermis, or that encoding of this error is via non-topographic means. [ABSTRACT FROM AUTHOR]

The superior colliculus receives a direct projection from retinal ganglion cells. In primates, it remains unknown if the same ganglion cells also supply the lateral geniculate nucleus. To address this issue, a double-label experiment was performed in two male macaques. The animals fixated a target while injection sites were scouted in the superior colliculus by recording and stimulating with a tetrode. Once suitable sites were identified, cholera toxin subunit B-Alexa Fluor 488 was injected via an adjacent micropipette. In a subsequent acute experiment, cholera toxin subunit B-Alexa Fluor 555 was injected into the lateral geniculate nucleus at matching retinotopic locations. After a brief survival period, ganglion cells were examined in retinal flatmounts. The percentage of double-labeled cells varied locally, depending on the relative efficiency of retrograde transport by each tracer and the precision of retinotopic overlap of injection sites in each target nucleus. In counting boxes with extensive overlap, 76–98% of ganglion cells projecting to the superior colliculus were double labeled. Cells projecting to the superior colliculus constituted 4.0–6.7% of the labeled ganglion cell population. In one particularly large zone, there were 5,746 cells labeled only by CTB-AF555, 561cells double labeled by CTB-AF555 and CTB-AF488, but no cell labeled only by CTB-AF488. These data indicate that retinal input to the macaque superior colliculus arises from a collateral axonal branch supplied by ∼5% of the ganglion cells that project to the lateral geniculate nucleus. Surprisingly, there exist no ganglion cells that project exclusively to the SC. [ABSTRACT FROM AUTHOR]

Physical insult to the central nervous system (CNS) such as during electrode insertion leads to reactive astrogliosis which in turn contributes to glial scarring (GS). To date, reducing GS in these settings has focused on pharmacological agents and variations in electrode material composition or implantation procedures, and the role of electrode surface topography has remained unexplored. Since proteoglycans, a major component of GS tissue, possesses very well‐defined (nano) topography, a role for stochastic nanoroughness in glial scar formation is theorized. Using an in vitro system, we provide proof of concept that on substrates possessing stochastic nanoroughness corresponding to that of healthy astrocytes, glial scar formation is significantly inhibited, and more importantly, can be even reversed, and it involves signaling via the stretch‐activated cation channel Piezo‐1. In vivo studies reveal an absence of astrocytes aggregation along the electrode track of chronically implanted electrodes modified with stochastic surface nanoroughness, compared to non‐modified electrodes, while signal detection within the superior colliculus remains unaffected. These findings shedlight on the crucial role of stochastic biophysical cues in modulating GS formation; and offer a promising non‐chemical approach for engineering neural biomaterials interface for the CNS. [ABSTRACT FROM AUTHOR]

Background: First-episode schizophrenia (FES) is a complex and progressive psychiatric disorder. The etiology of FES involves genetic, environmental, and neurobiological factors. This study investigates the association between alterations in structural–functional (SC-FC) coupling and transcriptional expression in FES. Methods: This study encompassed a cohort of 214 participants, comprising 111 FES patients and 103 healthy controls (HC). Furthermore, we examined the abnormalities within SC-FC coupling in FES and their correlations with meta-analytic cognitive terms, neurotransmitters, and transcriptional patterns through partial least squares regression (PLS), involving similarity with other psychiatric disorders or psychiatric-related diseases, functional enrichments, special cell types, peripheral inflammation, and cortical layers. Results: FES patients exhibited lower SC-FC coupling in the visual, sensorimotor, and ventral attention networks compared to controls. Furthermore, case–control t-maps revealed a negative correlation with neurotransmitters such as serotonin and dopamine, while showing a positive correlation with opioids. Positive t-maps were associated with cognitive functions, including reasoning, judgment, and action, whereas negative t-maps correlated with cognitive functions such as learning, stress, and mood. Moreover, there was a significant overlap between genes linked to abnormalities in SC-FC coupling and those dysregulated in inflammatory bowel diseases. PLS2- genes linked to SC-FC coupling demonstrated significant enrichment in pathways related to immunity and inflammation, as well as in cortical layers I and V. Conversely, PLS2 + genes were primarily enriched in synaptic signaling processes, specific excitatory neurons, and layers II and IV. Additionally, changes in SC-FC coupling were negatively associated with gene expression related to antipsychotics and lymphocytes. Conclusions: These findings offer a new perspective on the complex interplay between SC-FC coupling abnormalities and transcriptional expression in the initial phases of schizophrenia. [ABSTRACT FROM AUTHOR]

Head direction (HD) neurons, signalling facing direction, generate a signal that is primarily anchored to the outside world by visual inputs. We investigated the route for visual landmark information into the HD system in rats. There are two candidates: an evolutionarily older, larger subcortical retino‐tectal pathway and a more recently evolved, smaller cortical retino‐geniculo‐striate pathway. We disrupted the cortical pathway by lesioning the dorsal lateral geniculate thalamic nuclei bilaterally, and recorded HD cells in the postsubicular cortex as rats foraged in a visual‐cue‐controlled enclosure. In lesioned rats we found the expected number of postsubicular HD cells. Although directional tuning curves were broader across a trial, this was attributable to the increased instability of otherwise normal‐width tuning curves. Tuning curves were also poorly responsive to polarizing visual landmarks and did not distinguish cues based on their visual pattern. Thus, the retino‐geniculo‐striate pathway is not crucial for the generation of an underlying, tightly tuned directional signal but does provide the main route for vision‐based anchoring of the signal to the outside world, even when visual cues are high in contrast and low in detail. Key points: Head direction (HD) cells indicate the facing direction of the head, using visual landmarks to distinguish directions.In rats, we investigated whether this visual information is routed through the thalamus to the visual cortex or arrives via the superior colliculus, which is a phylogenetically older and (in rodents) larger pathway.We lesioned the thalamic dorsal lateral geniculate nucleus (dLGN) in rats and recorded the responsiveness of cortical HD cells to visual cues.We found that cortical HD cells had normal tuning curves, but these were slightly more unstable during a trial. Most notably, HD cells in dLGN‐lesioned animals showed little ability to distinguish highly distinct cues and none to distinguish more similar cues.These results suggest that directional processing of visual landmarks in mammals requires the geniculo‐cortical pathway, which raises questions about when and how visual directional landmark processing appeared during evolution. [ABSTRACT FROM AUTHOR]

Adaptation of reactive saccades (RS), made toward the sudden appearance of stimuli in our environment, is a plastic mechanism thought to occur at the motor level of saccade generation. As saccadic oculomotor commands integrate multisensory information in the parietal cortex and superior colliculus, adaptation of RS should occur not only toward visual but also tactile targets. In addition, saccadic adaptation in one modality (vision or touch) should transfer cross-modally. To test these predictions, we used the double-step target paradigm to adapt rightward saccades made at two different eccentricities toward the participants' index and middle fingers, identified either visually (experiment 1) or tactually (experiment 2). In each experiment, the rate of adaptation induced for the adapted modality and the rate of adaptation transfer to the nonadapted modality were compared with that measured in a control (no adaptation) session. Results revealed that touch-triggered RS can be adapted as well as visually triggered ones. Moreover, the transfer pattern was asymmetric: visual saccadic adaptation transferred fully to tactile saccades, whereas tactile saccadic adaptation, despite full generalization to nonadapted fingers, transferred only partially to visual saccades. These findings disclose that in the case of tactile saccades, adaptation can be elicited in the absence of postsaccadic visual feedback. In addition, the asymmetric adaptation transfer across sensory modalities suggests that the adaptation locus for tactile saccades may occur in part upstream of the final motor pathway common to all saccades. These findings bring new insights both on the functional loci(us) and on the error signals of RS adaptation. NEW & NOTEWORTHY: The present study revealed that, as predicted from a large literature, adaptation of visual reactive saccades transfers to tactile saccades of the same as well as neighboring amplitudes. Furthermore, in a modified double-step target paradigm, tactile saccades exposed to repeated errors adapt with a similar rate and spatial generalization as visual saccades, but this adaptation only slightly transfers to visual saccades. These findings bring new information on saccadic adaptation processes. [ABSTRACT FROM AUTHOR]

The development of the visual system is a complex and multistep process characterized by the precise wiring of retinal ganglion cell (RGC) axon terminals with their corresponding neurons in the visual nuclei of the brain. Upon reaching primary image-forming nuclei (IFN), such as the superior colliculus and the lateral geniculate nucleus, RGC axons undergo extensive arborization that refines over the first few postnatal weeks. The molecular mechanisms driving this activity-dependent remodeling process, which is influenced by waves of spontaneous activity in the developing retina, are still not well understood. In this study, by manipulating the activity of RGCs in mice from either sex and analyzing their transcriptomic profiles before eye-opening, we identified the Type I membrane protein synaptotagmin 13 (Syt13) as involved in spontaneous activity-dependent remodeling. Using these mice, we also explored the impact of spontaneous retinal activity on the development of other RGC recipient targets such as nonimageforming (NIF) nuclei and demonstrated that proper frequency and duration of retinal waves occurring prior to visual experience are essential for shaping the connectivity of the NIF circuit. Together, these findings contribute to a deeper understanding of the molecular and physiological mechanisms governing activity-dependent axon refinement during the assembly of the visual circuit. [ABSTRACT FROM AUTHOR]

It has been documented that caspase 3 activity is necessary for skeletal muscle regeneration, but how its activity is regulated is largely unknown. Our previous report shows that intracellular TMEM16A, a calcium activated chloride channel, significantly regulates caspase 3 activity in myoblasts during skeletal muscle development. By using a mouse line with satellite cell (SC)-specific deletion of TMEM16A, we examined the role of TMEM16A in regulating caspase 3 activity in SC (or SC-derived myoblast) as well as skeletal muscle regeneration. The mutant animals displayed apparently impaired regeneration capacity in adult muscle along with enhanced ER stress and elevated caspase 3 activity in Tmem16a−/− SC derived myoblasts. Blockade of either excessive ER stress or caspase 3 activity by small molecules significantly restored the inhibited myogenic differentiation of Tmem16a−/− SCs, indicating that excessive caspase 3 activity resulted from TMEM16A deletion contributes to the impaired muscle regeneration and the upstream regulator of caspase 3 was ER stress. Our results revealed an essential role of TMEM16A in satellite cell-mediated skeletal muscle regeneration by ensuring a moderate level of caspase 3 activity. [ABSTRACT FROM AUTHOR]

Abstract Objective This study measured eye movements in children with a history of opsoclonus‐myoclonus ataxia syndrome in order to identify abnormalities in saccade and pupil behavior that map onto specific alterations in brainstem pathways. Methods We used video‐based eye tracking while participants freely viewed 10 min of short (2–4 s) video clips without instructions. Clip transitions represented a large visual perturbation and we quantified multiple characteristics of saccade and pupil responses following these transitions in 13 children recovering from opsoclonus‐myoclonus and 13 healthy, age‐matched control participants. Results The frequency of saccades and distribution of fixation durations differed between the groups. Following the clip transitions, children recovering from opsoclonus‐myoclonus ataxia syndrome exhibited longer time to initiate saccades, leading to a delay in harvesting visual information. Clip transitions to lighter clips produced similar pupil constriction responses in the two groups. However, clip transitions to darker clips produced dilation responses that were initiated earlier and of greater magnitude in opsoclonus‐myoclonus ataxia syndrome, suggesting removal or suppression of a signal that delays dilation. Interpretation Children with a history of opsoclonus‐myoclonus ataxia syndrome demonstrated key abnormalities in saccade and pupil metrics. We propose a novel hypothesis in which dysfunction in the pathway from the superior colliculus to the mesencephalic and pontine reticular formation that houses the saccade and pupil premotor circuits could produce these results.

The superior colliculus (SC) has been increasingly implicated in the rapid processing of evolutionarily relevant stimuli like faces, but the behavioural relevance of such processing is unclear. The SC has also been implicated in the generation of express visuomotor responses (EVR), which are very short‐latency (~80 ms) bursts of muscle activity time‐locked to visual target presentation. These observations led us to investigate the influence of faces on EVRs. We recorded upper limb muscle activity from healthy participants as they reached toward targets in the presence of a distractor. In some experiments, faces were used as stimuli. Across blocks of trials, we varied the instruction as to which stimulus served as the target or distractor. Doing so allowed us to assess the impact of instruction on muscle recruitment given identical visual stimuli. We found that responses were uniquely modulated in tasks involving high‐contrast faces, promoting reaches toward or away from a face depending on instruction. Follow‐up experiments confirmed that the phenomenon required highly salient repeated faces and was not observed to non‐facial stimuli nor to faces expressing different affects. This study extends the hypothesis that the SC mediates the EVR by demonstrating that faces impact muscle recruitment at short latencies that precede cortical activity for face perception. Our results constitute direct evidence for the behavioural relevance of face detection in the brainstem, and also implicate a role for top‐down cortical pre‐setting of the EVR depending on task context. [ABSTRACT FROM AUTHOR]

The thermal vibration and buckling behavior of a functionally graded nanoplate are examined in this study. The nanoplate is made up of a silicon nitride/stainless steel core plate and two cobalt-ferrite/barium-titanate face plates. Four alternative porosity models were used to simulate the porosity of the nanoplate, and numerous variables that can affect the nanoplate's behavior were taken into account. The study found that the thermomechanical behavior of nanoplates with magneto-electro-elastic face layers and a functionally graded porous core plate is affected by material gradation indices, porosity ratios, nonlocal variables, and different core plate material porosity models. [ABSTRACT FROM AUTHOR]

Neural Crest cells (NC) are a multipotent cell population that give rise to a multitude of cell types including Schwann cells (SC) in the peripheral nervous system (PNS). Immature SC interact with neuronal axons via the neuregulin 1 (NRG1) ligand present on the neuronal surface and ultimately form the myelin sheath. Multiple attempts to derive functional SC from pluripotent stem cells have met challenges with respect to expression of mature markers and axonal sorting. Here, they hypothesized that sustained signaling from immobilized NRG1 (iNRG1) might enhance the differentiation of NC derived from glabrous neonatal epidermis towards a SC phenotype. Using this strategy, NC derived SC expressed mature markers to similar levels as compared to explanted rat sciatic SC. Signaling studies revealed that sustained NRG1 signaling led to yes‐associated protein 1 (YAP) activation and nuclear translocation. Furthermore, NC derived SC on iNRG1 exhibited mature SC function as they aligned with rat dorsal root ganglia (DRG) neurons in an in vitro coculture model; and most notably, aligned on neuronal axons upon implantation in a chick embryo model in vivo. Taken together their work demonstrated the importance of signaling dynamics in SC differentiation, aiming towards development of drug testing platforms for de‐myelinating disorders. [ABSTRACT FROM AUTHOR]

Skin cancer (SC) is an important medical condition that necessitates prompt identification to ensure timely treatment. Although visual evaluation by dermatologists is considered the most reliable method, its efficacy is subjective and laborious. Deep learning-based computer-aided diagnostic (CAD) platforms have become valuable tools for supporting dermatologists. Nevertheless, current CAD tools frequently depend on Convolutional Neural Networks (CNNs) with huge amounts of deep layers and hyperparameters, single CNN model methodologies, large feature space, and exclusively utilise spatial image information, which restricts their effectiveness. This study presents SCaLiNG, an innovative CAD tool specifically developed to address and surpass these constraints. SCaLiNG leverages a collection of three compact CNNs and Gabor Wavelets (GW) to acquire a comprehensive feature vector consisting of spatial–textural–frequency attributes. SCaLiNG gathers a wide range of image details by breaking down these photos into multiple directional sub-bands using GW, and then learning several CNNs using those sub-bands and the original picture. SCaLiNG also combines attributes taken from various CNNs trained with the actual images and subbands derived from GW. This fusion process correspondingly improves diagnostic accuracy due to the thorough representation of attributes. Furthermore, SCaLiNG applies a feature selection approach which further enhances the model's performance by choosing the most distinguishing features. Experimental findings indicate that SCaLiNG maintains a classification accuracy of 0.9170 in categorising SC subcategories, surpassing conventional single-CNN models. The outstanding performance of SCaLiNG underlines its ability to aid dermatologists in swiftly and precisely recognising and classifying SC, thereby enhancing patient outcomes. [ABSTRACT FROM AUTHOR]

Wolfram syndrome (WS) is a rare childhood disease characterized by diabetes mellitus, diabetes insipidus, blindness, deafness, neurodegeneration and eventually early death, due to autosomal recessive mutations in the WFS1 (and WFS2) gene. While it is categorized as a neurodegenerative disease, it is increasingly becoming clear that other cell types besides neurons may be affected and contribute to the pathogenesis. MRI studies in patients and phenotyping studies in WS rodent models indicate white matter/myelin loss, implicating a role for oligodendroglia in WS-associated neurodegeneration. In this study, we sought to determine if oligodendroglia are affected in WS and whether their dysfunction may be the primary cause of the observed optic neuropathy and brain neurodegeneration. We demonstrate that 7.5-month-old Wfs1∆exon8 mice display signs of abnormal myelination and a reduced number of oligodendrocyte precursor cells (OPCs) as well as abnormal axonal conduction in the optic nerve. An MRI study of the brain furthermore revealed grey and white matter loss in the cerebellum, brainstem, and superior colliculus, as is seen in WS patients. To further dissect the role of oligodendroglia in WS, we performed a transcriptomics study of WS patient iPSC-derived OPCs and pre-myelinating oligodendrocytes. Transcriptional changes compared to isogenic control cells were found for genes with a role in ER function. However, a deep phenotyping study of these WS patient iPSC-derived oligodendroglia unveiled normal differentiation, mitochondria-associated endoplasmic reticulum (ER) membrane interactions and mitochondrial function, and no overt signs of ER stress. Overall, the current study indicates that oligodendroglia functions are largely preserved in the WS mouse and patient iPSC-derived models used in this study. These findings do not support a major defect in oligodendroglia function as the primary cause of WS, and warrant further investigation of neurons and neuron-oligodendroglia interactions as a target for future neuroprotective or -restorative treatments for WS. [ABSTRACT FROM AUTHOR]

Background: Prepulse inhibition (PPI) is a phenomenon where a weak prepulse stimulus inhibits the startle reflex to a subsequent stronger stimulus, which can be induced by various sensory stimulus modalities such as visual, tactile, and auditory stimuli. Methods: This study investigates the neural mechanisms underlying auditory PPI by focusing on the deep layers of the superior colliculus (deepSC) and the inferior colliculus (IC) in rats. Nineteen male Sprague-Dawley rats were implanted with electrodes in the left deepSC and the right IC, and electrophysiological recordings were conducted under anesthesia to observe the frequency following responses (FFRs) to startle stimuli with and without prepulse stimuli. Results: Our results showed that in the deepSC, narrowband noise as a prepulse stimulus significantly inhibited the envelope component of the startle response, while the fine structure component remained unaffected. However, this inhibitory effect was not observed in the IC or when the prepulse stimulus was a gap. Conclusion: These findings suggest that the deepSC plays a crucial role in the neural circuitry of PPI, particularly in the modulation of the envelope component of the startle response. The differential effects of narrowband noise and gap as prepulse stimuli also indicate distinct neural pathways for sound-induced PPI and Gap-PPI. Understanding these mechanisms could provide insights into sensory processing and potential therapeutic targets for disorders involving impaired PPI, such as tinnitus. [ABSTRACT FROM AUTHOR]

The human brain is sensitive to threat-related information even when we are not aware of this information. For example, fearful faces attract gaze in the absence of visual awareness. Moreover, information in different sensory modalities interacts in the absence of awareness, for example, the detection of suppressed visual stimuli is facilitated by simultaneously presented congruent sounds or tactile stimuli. Here, we combined these two lines of research and investigated whether threat-related sounds could facilitate visual processing of threat-related images suppressed from awareness such that they attract eye gaze. We suppressed threat-related images of cars and neutral images of human hands from visual awareness using continuous flash suppression and tracked observers' eye movements while presenting congruent or incongruent sounds (finger snapping and car engine sounds). Indeed, threat-related car sounds guided the eyes toward suppressed car images, participants looked longer at the hidden car images than at any other part of the display. In contrast, neither congruent nor incongruent sounds had a significant effect on eye responses to suppressed finger images. Overall, our results suggest that only in a dangerrelated context semantically congruent sounds modulate eye movements to images suppressed from awareness, highlighting the prioritisation of eye responses to threat-related stimuli in the absence of visual awareness. [ABSTRACT FROM AUTHOR]

The rat lateral posterior thalamic nucleus (LP) is composed of the rostromedial (LPrm), lateral (LPl), and caudomedial parts, with LPrm and LPl being areas involved in information processing within the visual cortex. Nevertheless, the specific differences in the subcortical projections to the LPrm and LPl remain elusive. In this study, we aimed to reveal the subcortical regions that project axon fibers to the LPl and LPrm using a retrograde neural tracer, Fluorogold (FG). After FG injection into the LPrm or LPl, the area was visualized immunohistochemically. Retrogradely labeled neurons from the LPrm were distributed in the retina and the region from the diencephalon to the medulla oblongata. Diencephalic labeling was found in the reticular thalamic nucleus (Rt), zona incerta (ZI), ventral lateral geniculate nucleus (LGv), intergeniculate leaflet (IGL), and hypothalamus. In the midbrain, prominent labeling was found in the periaqueductal gray (PAG) and deep layers of the superior colliculus. Additionally, retrograde labeling was observed in the cerebellar and trigeminal nuclei. When injected into the LPl, several cell bodies were labeled in the visual-related regions, including the retina, LGv, IGL, and olivary pretectal nucleus (OPT), as well as in the Rt and anterior pretectal nucleus (APT). Less labeling was found in the cerebellum and medulla oblongata. When the number of retrogradely labeled neurons from the LPrm or LPl was compared as a percentage of total subcortical labeling, a larger percentage of subcortical inputs to the LPl included projections from the APT, OPT, and Rt, whereas a large proportion of subcortical inputs to the LPrm originated from the ZI, reticular formation, and PAG. These results suggest that LPrm not only has visual but also multiple sensory-and motor-related functions, whereas the LPl takes part in a more visual-specific role. This study enhances our understanding of subcortical neural circuits in the thalamus and may contribute to our exploration of the mechanisms and disorders related to sensory perception and sensory-motor integration. [ABSTRACT FROM AUTHOR]

Objective: While there are a wide range of approaches for the assessment of skin hydration, it is not always clear how data from them relate to one another or to the skin itself. With the development of in vivo Confocal Raman Spectroscopy (ICRS), it has become possible to measure water concentration as a function of protein/depth within the stratum corneum (SC). This article reports a comparison between electrical skin hydration measures/visual/optical grading and water concentration profiles measured using ICRS, to better understand the relationship between these approaches. Methods: SC hydration of lower‐leg skin with varying degrees of dryness was assessed using visual grading (live and from digital images), Corneometer®, Visioscan and ICRS. In addition, a custom fingerprint sensor was used to image surface capacitance (as a surrogate of SC hydration), and SC barrier function was assessed using evaporimetry (to measure trans‐epidermal water loss; TEWL). Results: Significant correlations were observed between a number of different skin grading/measurement approaches and ICRS data. ICRS hydration profiles also revealed a region near the SC surface with a relatively flat water profile in dry skin subjects. Conclusions: The advent of quantitative in vivo analytical techniques such as ICRS, which can be used in a clinical setting, has enabled greater insight into more conventional approaches for assessing skin dryness. While traditional skin grading and biophysical methods for measuring skin hydration have varying degrees of correlation with one another, they also provide comparatively unique information about different regions within the SC. This should enable a more informed approach to product development in the future. [ABSTRACT FROM AUTHOR]

It has been suggested that, prior to a saccade, visual neurons predictively respond to stimuli that will fall in their receptive fields after completion of the saccade. This saccadic remapping process is thought to compensate for the shift of the visual world across the retina caused by eye movements. To map the timing of this predictive process in the brain, we recorded neural activity using electroencephalography during a saccade task. Human participants (male and female) made saccades between two fixation points while covertly attending to oriented gratings briefly presented at various locations on the screen. Data recorded during trials in which participants maintained fixation were used to train classifiers on stimuli in different positions. Subsequently, data collected during saccade trials were used to test for the presence of remapped stimulus information at the post-saccadic retinotopic location in the peri-saccadic period, providing unique insight into when remapped information becomes available. We found that the stimulus could be decoded at the remapped location ~180 ms post-stimulus onset, but only when the stimulus was presented 100-200 ms before saccade onset. Within this range, we found that the timing of remapping was dictated by stimulus onset rather than saccade onset. We conclude that presenting the stimulus immediately before the saccade allows for optimal integration of the corollary discharge signal with the incoming peripheral visual information, resulting in a remapping of activation to the relevant post-saccadic retinotopic neurons. [ABSTRACT FROM AUTHOR]

When interacting with the visual world using saccadic eye movements (saccades), the perceived location of visual stimuli becomes biased, a phenomenon called perisaccadic mislocalization. However, the neural mechanism underlying this altered visuospatial perception and its potential link to other perisaccadic perceptual phenomena have not been established. Using the electrophysiological recording of extrastriate areas in four male macaque monkeys, combined with a computational model, we were able to quantify spatial bias around the saccade target (ST) based on the perisaccadic dynamics of extrastriate spatiotemporal sensitivity captured by a statistical model. This approach could predict the perisaccadic spatial bias around the ST, consistent with behavioral data, and revealed the precise neuronal response components underlying representational bias. These findings also establish the crucial role of increased sensitivity near the ST for neurons with receptive fields far from the ST in driving the ST spatial bias. Moreover, we showed that, by allocating more resources for visual target representation, visual areas enhance their representation of the ST location, even at the expense of transient distortions in spatial representation. This potential neural basis for perisaccadic ST representation also supports a general role for extrastriate neurons in creating the perception of stimulus location. The neural basis of perisaccadic changes in spatial perception is unknown. Here, the authors reveal a potential neural basis for the perisaccadic bias in perceived location linked to saccade target representational enhancement in extrastriate areas. [ABSTRACT FROM AUTHOR]

The arthropod mushroom body is well-studied as an expansion layer representing olfactory stimuli and linking them to contingent events. However, 8% of mushroom body Kenyon cells in Drosophila melanogaster receive predominantly visual input, and their function remains unclear. Here, we identify inputs to visual Kenyon cells using the FlyWire adult whole-brain connectome. Input repertoires are similar across hemispheres and connectomes with certain inputs highly overrepresented. Many visual neurons presynaptic to Kenyon cells have large receptive fields, while interneuron inputs receive spatially restricted signals that may be tuned to specific visual features. Individual visual Kenyon cells randomly sample sparse inputs from combinations of visual channels, including multiple optic lobe neuropils. These connectivity patterns suggest that visual coding in the mushroom body, like olfactory coding, is sparse, distributed, and combinatorial. However, the specific input repertoire to the smaller population of visual Kenyon cells suggests a constrained encoding of visual stimuli. The Drosophila mushroom body, a well-studied olfactory learning center, also receives visual input with unknown function. Here, the authors leverage the FlyWire connectome to identify and characterize properties of visual inputs to the mushroom body. [ABSTRACT FROM AUTHOR]

Objective(s): This study aimed to examine the influence of changes in CT values on PET images, specifically focusing on errors in CT-based attenuation correction and scatter coincidence correction (CTAC/SC) caused by gastrointestinal gas. Furthermore, it aimed to demonstrate the effectiveness of time-of-flight (TOF) PET in reducing CTAC/SC errors. Methods: PET images were reconstructed using multiple CT images with varying CT values. The study then compared the fluctuations in pixel values of the PET images corresponding to the different CT values utilized for CTAC/SC between non-TOF and TOF acquisitions. Results: PET pixel values fluctuated with changes in CT values. In the phantom study, TOF showed a significantly smaller change in PET pixel value of 1.00±0.27 kBq/mL compared to 3.72±1.33 kBq/mL in the non-TOF at sites with a CT change of +1000 HU. In the patient study, a linear regression analysis was performed to determine the effect of changes in CT values due to gastrointestinal gas migration on standard uptake value (SUV).The results showed that the TOF group had a lower ratio of change in SUV to change in CT values compared to the non-TOF group. These findings revealed that PET pixel values exhibited fluctuations in response to changes in CT values, and TOF-PET effectively mitigated CTAC/SC errors arising from gastrointestinal gas. Conclusions: TOF-PET has the potential to reduce the occurrence of suspicious accumulation. [ABSTRACT FROM AUTHOR]

The role of nitrergic system in modulating the action of psychostimulants on reward processing is well established. However, the relevant anatomical underpinnings and scope of the involved interactions with mesolimbic dopaminergic system have not been clarified. Using immunohistochemistry, we track the changes in neuronal nitric oxide synthase (nNOS) containing cell groups in the animals conditioned to intracranial self‐stimulation (ICSS) via an electrode implanted in the lateral hypothalamus‐medial forebrain bundle (LH‐MFB) area. An increase in the nNOS immunoreactivity was noticed in the cells and fibers in the ventral tegmental area (VTA) and nucleus accumbens shell (AcbSh), the primary loci of the reward system. In addition, nNOS was up‐regulated in the nucleus accumbens core (AcbC), vertical limb of diagonal band (VDB), locus coeruleus (LC), lateral hypothalamus (LH), superficial gray layer (SuG) of the superior colliculus, and periaqueductal gray (PAG). The brain tissue fragments drawn from these areas showed a change in nNOS mRNA expression, but in opposite direction. Intracerebroventricular (icv) administration of nNOS inhibitor, 7‐nitroindazole (7‐NI) showed decreased lever press activity in a dose‐dependent manner in ICSS task. While an increase in the dopamine (DA) and 3, 4‐dihydroxyphenylacetic acid (DOPAC) efflux was noted in the microdialysates collected from the AcbSh of ICSS rats, pre‐administration of 7‐NI (icv route) attenuated the response. The study identifies nitrergic centers that probably mediate sensory, cognitive, and motor components of the goal‐directed behavior. [ABSTRACT FROM AUTHOR]

Muscle isometric torque fluctuates according to time-of-day with such variation owed to the influence of circadian molecular clock genes. Satellite cells (SCs), the muscle stem cell population, also express molecular clock genes with several contractile-related genes oscillating in a diurnal pattern. Currently, limited evidence exists regarding the relationship between SCs and contractility, although long-term SC ablation alters muscle contractile function. Whether there are acute alterations in contractility following SC ablation and with respect to the time-of-day is unknown. We investigated whether short-term SC ablation affected contractile function at two times of day and whether any such alterations led to different extents of eccentric contraction-induced injury. Using an established mouse model to deplete SCs, we characterized muscle clock gene expression and ex vivo contractility at two times-of-day (morning: 0700 and afternoon: 1500). Morning-SC+ animals demonstrated ∼25%–30% reductions in tetanic/eccentric specific forces and, after eccentric injury, exhibited ∼30% less force-loss and ∼50% less dystrophinnegative fibers versus SC− counterparts; no differences were noted between Afternoon groups (Morning-SC+: −5.63 ± 0.61, Morning-SC−: −7.93 ± 0.61; N/cm2; P < 0.05) (Morning-SC+: 32 ± 2.1, Morning-SC−: 64 ± 10.2; dystrophinnegative fibers; P < 0.05). As Ca++ kinetics underpin force generation, we also evaluated caffeine-induced contracture force as an indirect marker of Ca++ availability and found similar force reductions in Morning-SC+ vs. SC− mice. We conclude that force production is reduced in the presence of SCs in the morning but not in the afternoon, suggesting that SCs may have a time-of-day influence over contractile function. NEW & NOTEWORTHY: Muscle isometric torque fluctuates according to time-of-day with such variation owed to molecular clock regulation. Satellite cells (SCs) have recently demonstrated diurnal characteristics related to muscle physiology. In our work, force production was reduced in the presence versus absence of SCs in the morning but, not in the afternoon. Morning-SC+ animals, producing lower force, sustained lesser degrees of injury versus SC− counterparts. One potential mechanism underpinning lower forces produced appears to be lower calcium availability. [ABSTRACT FROM AUTHOR]

The superficial layers of the mammalian superior colliculus (SC) contain neurons that are generally responsive to visual stimuli but can differ considerably in morphology and response properties. To elucidate the structure and function of these neurons, we combined extracellular recording and juxtacellular labeling, detailed anatomical reconstruction, and ultrastructural analysis of the synaptic contacts of labeled neurons, using transmission electron microscopy. Our labeled neurons project to different brainstem nuclei. Of particular importance are neurons that fit the morphological criteria of the wide field (WF) neurons and whose dendrites are horizontally oriented. They display a rather characteristic axonal projection pattern to the nucleus of optic tract (NOT); thus, we call them superior collicular WF projecting to the NOT (SCWFNOT) neurons. We corroborated the morphological characterization of this neuronal type as a distinct neuronal class with the help of unsupervised hierarchical cluster analysis. Our ultrastructural data demonstrate that SCWFNOT neurons establish excitatory connections with their targets in the NOT. Although, in rodents, the literature about the WF neurons has focused on their extensive projection to the lateral posterior nucleus of the thalamus, as a conduit for information to reach the visual association areas of the cortex, our data suggest that this subclass of WF neurons may participate in the optokinetic nystagmus. [ABSTRACT FROM AUTHOR]

The physiological aging process is well known for functional decline in visual abilities. Among the components of the visual system, the dorsal lateral geniculate nucleus (DLG) and superior colliculus (SC) provide a good model for aging investigations, as these structures constitute the main visual pathways for retinal inputs reaching the visual cortex. However, there are limited data available on quantitative morphological and neurochemical aspects in DLG and SC across lifespan. Here, we used optical density to determine immunoexpression of glial fibrillary acidic protein (GFAP) and design‐based stereological probes to estimate the neuronal number, total volume, and layer volume of the DLG and SC in marmosets (Callithrix jacchus), ranging from 36 to 143 months of age. Our results revealed an age‐related increase in total volume and layer volume of the DLG, with an overall stability in SC volume. Furthermore, a stable neuronal number was demonstrated in DLG and superficial layers of SC (SCv). A decrease in GFAP immunoexpression was observed in both visual centers. The results indicate region‐specific variability in volumetric parameter, possibly attributed to structural plastic events in response to inflammation and compensatory mechanisms at the cellular and subcellular level. Additionally, the DLG and SCv seem to be less vulnerable to aging effects in terms of neuronal number. The neuropeptidergic data suggest that reduced GFAP expression may reflect morphological atrophy in the astroglial cells. This study contributes to updating the current understanding of aging effects in the visual system and stablishes a crucial foundation for future research on visual perception throughout the aging process. [ABSTRACT FROM AUTHOR]

Conventional contact-based hand signature recognition methods are raising hygienic concerns due to shared acquisition devices among the public. Therefore, this research aimed to propose a contactless in-air hand gesture signature (iHGS) recognition method using convolutional recurrent neural networks (C-RNN). Experiments have been conducted to identify the most suitable CNN architecture for the integration of CNN and RNN. A total of four base architectures were adopted and evaluated, namely MS-CNN-A, MS-CNN-B, CNN-A, and CNN-B. Based on the results, CNN-A was selected as the convolutional layer for constructing the integration of C-RNN due to its superior performance, achieving an accuracy rate of 95.15%. Furthermore, three variants of C-RNN were proposed, and experimental results on the iHGS database showed that the ConvBiLSTM achieved the highest accuracy at 98.10%, followed by ConvGRU at 97.47% and ConvLSTM at 97.40%. [ABSTRACT FROM AUTHOR]

Background: In recent years, the scientific community has been captivated by the intriguing Autonomous sensory meridian response (ASMR), a unique phenomenon characterized by tingling sensations originating from the scalp and propagating down the spine. While anecdotal evidence suggests the therapeutic potential of ASMR, the field has witnessed a surge of scientific interest, particularly through the use of neuroimaging techniques including functional magnetic resonance imaging (fMRI) as well as electroencephalography (EEG) and physiological measures such as eye tracking (Pupil Diameter), heart rate (HR), heartbeat-evoked potential (HEP), blood pressure (BP), pulse rates (PR), finger photoplethysmography (PPG), and skin conductance (SC). This article is intended to provide a comprehensive overview of technology's contributions to the scientific elucidation of ASMR mechanisms. Methodology: A meticulous literature review was undertaken to identify studies that have examined ASMR using EEG and physiological measurements. The comprehensive search was conducted across databases such as PUBMED, SCOPUS, and IEEE, using a range of relevant keywords such as 'ASMR', 'Autonomous sensory meridian response', 'EEG', 'fMRI', 'electroencephalography', 'physiological measures', 'heart rate', 'skin conductance', and 'eye tracking'. This rigorous process yielded a substantial number of 63 PUBMED and 166 SCOPUS-related articles, ensuring the inclusion of a wide range of high-quality research in this review. Results: The review uncovered a body of research utilizing EEG and physiological measures to explore ASMR's effects. EEG studies have revealed distinct patterns of brain activity associated with ASMR experiences, particularly in regions implicated in emotional processing and sensory integration. In physiological measurements, a decrease in HR and an increase in SC and pupil diameter indicate relaxation and increased attention during ASMR-triggered stimuli. Conclusions: The findings of this review underscore the significance of EEG and physiological measures in unraveling the psychological and physiological effects of ASMR. ASMR experiences have been associated with unique neural signatures, while physiological measures provide valuable insights into the autonomic responses elicited by ASMR stimuli. This review not only highlights the interdisciplinary nature of ASMR research but also emphasizes the need for further investigation to elucidate the mechanisms underlying ASMR and explore its potential therapeutic applications, thereby paving the way for the development of novel therapeutic interventions. [ABSTRACT FROM AUTHOR]

Significance: Many techniques exist for screening retinal phenotypes in mouse models in vision research, but significant challenges remain for efficiently probing higher visual centers of the brain. Photoacoustic computed tomography (PACT), with optical sensitivity to hemodynamic response (HR) in brain and ultrasound resolution, provides unique advantages in comprehensively assessing higher visual function in the mouse brain. Aim: We aim to examine the reliability of PACT in the functional phenotyping of mouse models for vision research. Approach: A PACT-ultrasound (US) parallel imaging system was established with a one-dimensional (1D) US transducer array and a tunable laser. Imaging was performed at three coronal planes of the brain, covering the primary visual cortex and the four subcortical nuclei, including the superior colliculus, the dorsal lateral geniculate nucleus, the suprachiasmatic nucleus, and the olivary pretectal nucleus. The visual-evoked HR was isolated from background signals using an impulsebased data processing protocol. rd1 mice with rod/cone degeneration, melanopsinknockout (mel-KO) mice with photoreceptive ganglion cells that lack intrinsic photosensitivity, and wild-type mice as controls were imaged. The quantitative characteristics of the visual-evoked HR were compared. Results: Quantitative analysis of the HRs shows significant differences among the three mouse strains: (1) rd1 mice showed both smaller and slower responses compared with wild type (n = 10;10, p < 0.01) and (2) mel-KO mice had lower amplitude but not significantly delayed photoresponses than wild-type mice (n = 10;10, p < 0.01). These results agree with the known visual deficits of the mouse strains. Conclusions: PACT demonstrated sufficient sensitivity to detecting post-retinal functional deficits. [ABSTRACT FROM AUTHOR]

Cortical responses to visual stimuli are believed to rely on the geniculo-striate pathway. However, recent work has challenged this notion by showing that responses in the postrhinal cortex (POR), a visual cortical area, instead depend on the tecto-thalamic pathway, which conveys visual information to the cortex via the superior colliculus (SC). Does PORs SC-dependence point to a wider system of tecto-thalamic cortical visual areas? What information might this system extract from the visual world? We discovered multiple mouse cortical areas whose visual responses rely on SC, with the most lateral showing the strongest SC-dependence. This system is driven by a genetically defined cell type that connects the SC to the pulvinar thalamic nucleus. Finally, we show that SC-dependent cortices distinguish self-generated from externally generated visual motion. Hence, lateral visual areas comprise a system that relies on the tecto-thalamic pathway and contributes to processing visual motion as animals move through the environment.

Seemingly simple behaviors such as swatting a mosquito or glancing at a signpost involve the precise coordination of multiple body parts. Neural control of coordinated movements is widely thought to entail transforming a desired overall displacement into displacements for each body part. Here we reveal a different logic implemented in the mouse gaze system. Stimulating superior colliculus (SC) elicits head movements with stereotyped displacements but eye movements with stereotyped endpoints. This is achieved by individual SC neurons whose branched axons innervate modules in medulla and pons that drive head movements with stereotyped displacements and eye movements with stereotyped endpoints, respectively. Thus, single neurons specify a mixture of endpoints and displacements for different body parts, not overall displacement, with displacements for different body parts computed at distinct anatomical stages. Our study establishes an approach for unraveling motor hierarchies and identifies a logic for coordinating movements and the resulting pose.

A slowly moving dark spot imitating the shadow of a hovering bird of prey has been shown to induce freezing in rodents. Such visually triggered behaviours are usually initiated in the superior colliculus (SC); therefore, it is likely that such slowly moving dark spots can produce responses in SC neurons. In SC, two types of visual responses are typically distinguished: ON responses are produced by an increase in image brightness, and OFF responses are produced by a decrease in image brightness. Typically, OFF responses are very brief, lasting only a few hundred milliseconds, and may be poorly suited for the detection of slowly moving dark spots. Here, we report that, in the majority of SC neurons of urethane-anaesthetized rats, in addition to these brief OFF responses, very slow OFF responses lasting over 5 s were present; thus, OFF responses that occurred > 1 s after the stimulus offset were termed ‘slow OFF’ response, while brief, less than 1 s long OFF responses were called ‘fast OFF’ response. Although the slow OFF responses were of similar amplitude as the fast OFF responses (∼5 Hz), the optimal size (producing the maximal response) was larger for the slow OFF responses (20° for the slow and 10° for the fast OFF responses). Correlation analysis revealed that both the fast and the slow components of the OFF response contribute to the response to a slowly moving spot. Elimination of visual cortex inputs increased the amplitude and duration of the slow OFF responses, indicating that they originate in the retina. It is concluded that in rodent SC, a new type of OFF response that is well suited for predator detection is present.

Eye-tracking techniques have gained widespread application in various fields including research on the visual system, neurosciences, psychology, and human-computer interaction, with emerging clinical implications. In this preliminary phase of our study, we introduce a pilot test of innovative virtual reality technology designed for tracking head and eye movements among healthy individuals. This tool was developed to assess the presence of mild traumatic brain injury (mTBI), given the frequent association of oculomotor function deficits with such injuries. Alongside eye-tracking, we also integrated fMRI due to the complementary nature of these techniques, offering insights into both neural activation patterns and behavioural responses, thereby providing a comprehensive understanding of oculomotor function. We used fMRI with tasks evaluating oculomotor functions: Smooth Pursuit (SP), Saccades, Anti-Saccades, and Optokinetic Nystagmus (OKN). Prior to the scanning, the testing with a system of VR goggles with integrated eye and head tracking was used where subjects performed the same tasks as those used in fMRI. 31 healthy adult controls (HCs) were tested with the purpose of identifying brain regions associated with these tasks and collecting preliminary norms for later comparison with concussed subjects. HCs' fMRI results showed following peak activation regions: SP–cuneus, superior parietal lobule, paracentral lobule, inferior parietal lobule (IPL), cerebellartonsil (CT); Saccades–middle frontal gyrus (MFG), postcentral gyrus, medial frontal gyrus; Anti-saccades—precuneus, IPL, MFG; OKN—middle temporal gyrus, ACC, postcentral gyrus, MFG, CT. These results demonstrated brain regions associated with the performance on oculomotor tasks in healthy controls and most of the highlighted areas are corresponding with those affected in concussion. This suggests that the involvement of brain areas susceptible to mTBI in implementing oculomotor evaluation, taken together with commonly reported oculomotor difficulties post-concussion, may lead to finding objective biomarkers using eye-tracking tasks. [ABSTRACT FROM AUTHOR]

Defining the brain mechanisms underlying initial emotional evaluation is a key but unexplored clue to understanding affective processing. Event-related potentials (ERPs), especially suited for investigating this issue, were recorded in two experiments (n = 36 and n = 35). We presented emotionally negative (spiders) and neutral (wheels) silhouettes homogenized regarding their visual parameters. In Experiment 1, stimuli appeared at fixation or in the periphery (200 trials per condition and location), the former eliciting a N40 (39 milliseconds) and a P80 (or C1: 80 milliseconds) component, and the latter only a P80. In Experiment 2, stimuli were presented only at fixation (500 trials per condition). Again, an N40 (45 milliseconds) was observed, followed by a P100 (or P1: 105 milliseconds). Analyses revealed significantly greater N40-C1P1 peak-to-peak amplitudes for spiders in both experiments, and ANCOVAs showed that these effects were not explained by C1P1 alone, but that processes underlying N40 significantly contributed. Source analyses pointed to V1 as an N40 focus (more clearly in Experiment 2). Sources for C1P1 included V1 (P80) and V2/LOC (P80 and P100). These results and their timing point to low-order structures (such as visual thalamic nuclei or superior colliculi) or the visual cortex itself, as candidates for initial evaluation structures. [ABSTRACT FROM AUTHOR]

Recent studies have highlighted neurons and their associated Schwann cells (SCs) as key regulators of cancer development. However, the mode of their interaction with tumor cells or other components of the tumor microenvironment (TME) remains elusive. We established an SC-related 43-gene set as a surrogate for peripheral nerves in the TME. Head and neck squamous cell carcinoma (HNSCC) from The Cancer Genome Atlas (TCGA) were classified into low, intermediate and high SC score groups based on the expression of this gene set. Perineural invasion (PNI) and TGF-β signaling were hallmarks of SChigh tumors, whereas SClow tumors were enriched for HPV16-positive OPSCC and higher PI3K-MTOR activity. The latter activity was partially explained by a higher frequency of PTEN mutation and PIK3CA copy number gain. The inverse association between PI3K-MTOR activity and peripheral nerve abundance was context-dependent and influenced by the TP53 mutation status. An in silico drug screening approach highlighted the potential vulnerabilities of HNSCC with variable SC scores and predicted a higher sensitivity of SClow tumors to DNA topoisomerase inhibitors. In conclusion, we have established a tool for assessing peripheral nerve abundance in the TME and provided new clinical and biological insights into their regulation. This knowledge may pave the way for new therapeutic strategies and impart proof of concept in appropriate preclinical models. [ABSTRACT FROM AUTHOR]

The quest to identify neural mechanisms of selective attention has broadened in recent years to include multiple forms of attention, multiple species, and multiple levels of analysis. New data reveal distinct and causal roles of the superior colliculus and parietal cortex in stimulus-driven visual attention. Convergent evidence across species has identified a role of motor-related signals in the control of goal-directed attention. Fluctuations in cortical activity associated with global arousal interact with goal-driven attention and both predict perceptual performance. Neural oscillations reflecting attentional control in human and non-human primates suggest an underlying rhythmic mechanism synchronized to theta. Despite a constant deluge of sensory stimulation, only a fraction of it is used to guide behavior. This selective processing is generally referred to as attention, and much research has focused on the neural mechanisms controlling it. Recently, research has broadened to include more ways by which different species selectively process sensory information, whether due to the sensory input itself or to different behavioral and brain states. This work has produced a complex and disjointed body of evidence across different species and forms of attention. However, it has also provided opportunities to better understand the breadth of attentional mechanisms. Here, we summarize the evidence that suggests that different forms of selective processing are supported by mechanisms both common and distinct. [ABSTRACT FROM AUTHOR]

We recently developed a biomimetic robotic eye with six independent tendons, each controlled by their own rotatory motor, and with insertions on the eye ball that faithfully mimic the biomechanics of the human eye. We constructed an accurate physical computational model of this system, and learned to control its nonlinear dynamics by optimising a cost that penalised saccade inaccuracy, movement duration, and total energy expenditure of the motors. To speed up the calculations, the physical simulator was approximated by a recurrent neural network (NARX). We showed that the system can produce realistic eye movements that closely resemble human saccades in all directions: their nonlinear main-sequence dynamics (amplitude-peak eye velocity and duration relationships), cross-coupling of the horizontal and vertical movement components leading to approximately straight saccade trajectories, and the 3D kinematics that restrict 3D eye orientations to a plane (Listing's law). Interestingly, the control algorithm had organised the motors into appropriate agonist-antagonist muscle pairs, and the motor signals for the eye resembled the well-known pulse-step characteristics that have been reported for monkey motoneuronal activity. We here fully analyse the eye-movement properties produced by the computational model across the entire oculomotor range and the underlying control signals. We argue that our system may shed new light on the neural control signals and their couplings within the final neural pathways of the primate oculomotor system, and that an optimal control principle may account for a wide variety of oculomotor behaviours. The generated data are publicly available at https://data.ru.nl/collections/di/dcn/DSC%5F626870%5F0003%5F 600. [ABSTRACT FROM AUTHOR]

The posterior parietal cortex (PPC) integrates multisensory and motor‐related information for generating and updating body representations and movement plans. We used retrograde transneuronal transfer of rabies virus combined with a conventional tracer in macaque monkeys to identify direct and disynaptic pathways to the arm‐related rostral medial intraparietal area (MIP), the ventral lateral intraparietal area (LIPv), belonging to the parietal eye field, and the pursuit‐related lateral subdivision of the medial superior temporal area (MSTl). We found that these areas receive major disynaptic pathways via the thalamus from the nucleus of the optic tract (NOT) and the superior colliculus (SC), mainly ipsilaterally. NOT pathways, targeting MSTl most prominently, serve to process the sensory consequences of slow eye movements for which the NOT is the key sensorimotor interface. They potentially contribute to the directional asymmetry of the pursuit and optokinetic systems. MSTl and LIPv receive feedforward inputs from SC visual layers, which are potential correlates for fast detection of motion, perceptual saccadic suppression and visual spatial attention. MSTl is the target of efference copy pathways from saccade‐ and head‐related compartments of SC motor layers and head‐related reticulospinal neurons. They are potential sources of extraretinal signals related to eye and head movement in MSTl visual‐tracking neurons. LIPv and rostral MIP receive efference copy pathways from all SC motor layers, providing online estimates of eye, head and arm movements. Our findings have important implications for understanding the role of the PPC in representation updating, internal models for online movement guidance, eye‐hand coordination and optic ataxia. [ABSTRACT FROM AUTHOR]

The superior colliculus (SC) is a prominent and conserved visual center in all vertebrates. In mice, the most superficial lamina of the SC is enriched with neurons that are selective for the moving direction of visual stimuli. Here, we study how these direction selective neurons respond to complex motion patterns known as plaids, using two-photon calcium imaging in awake male and female mice. The plaid pattern consists of two superimposed sinusoidal gratings moving in different directions, giving an apparent pattern direction that lies between the directions of the two component gratings. Most direction selective neurons in the mouse SC respond robustly to the plaids and show a high selectivity for the moving direction of the plaid pattern but not of its components. Pattern motion selectivity is seen in both excitatory and inhibitory SC neurons and is especially prevalent in response to plaids with large cross angles between the two component gratings. However, retinal inputs to the SC are ambiguous in their selectivity to pattern versus component motion. Modeling suggests that pattern motion selectivity in the SC can arise from a nonlinear transformation of converging retinal inputs. In contrast, the prevalence of pattern motion selective neurons is not seen in the primary visual cortex (V1). These results demonstrate an interesting difference between the SC and V1 in motion processing and reveal the SC as an important site for encoding pattern motion. [ABSTRACT FROM AUTHOR]

The superior colliculus receives powerful synaptic inputs from corticotectal neurons in the visual cortex. The function of these corticotectal neurons remains largely unknown due to a limited understanding of their response properties and connectivity. Here, we use antidromic methods to identify corticotectal neurons in awake male and female rabbits, and measure their axonal conduction times, thalamic inputs and receptive field properties. All corticotectal neurons responded to sinusoidal drifting gratings with a nonlinear (nonsinusoidal) increase in mean firing rate but showed pronounced differences in their ON-OFF receptive field structures that we classified into three groups, Cx, S2, and S1. Cx receptive fields had highly overlapping ON and OFF subfields as classical complex cells, S2 had largely separated ON and OFF subfields as classical simple cells, and S1 had a single ON or OFF subfield. Thus, all corticotectal neurons are homogeneous in their nonlinear spatial summation but very heterogeneous in their spatial integration of ON and OFF inputs. The Cx type had the fastest conducting axons, the highest spontaneous activity, and the strongest and fastest visual responses. The S2 type had the highest orientation selectivity, and the S1 type had the slowest conducting axons. Moreover, our cross-correlation analyses found that a subpopulation of corticotectal neurons with very fast conducting axons and high spontaneous firing rates (largely “Cx” type) receives monosynaptic input from retinotopically aligned thalamic neurons. This previously unrecognized fast-conducting thalamic-mediated corticotectal pathway may provide specialized information to superior colliculus and prime recipient neurons for subsequent corticotectal or retinal synaptic input. [ABSTRACT FROM AUTHOR]

• Volitional signals for gaze control provided by multiple parallel pathways to the superior colliculus (88) • Interaction of sensory task-related signals within the multi-layered superior colliculus (79) • Convergence of bottom-up (world statistics) and top-down (goal and task) signals in the SC for gaze control (91) • Models of attention such as saliency map and their physiological basis (60) • Cerebral and subcortical inputs to control output signals for gaze in the SC (64) Volitional signals for gaze control are provided by multiple parallel pathways converging on the midbrain superior colliculus (SC), whose deeper layers output to the brainstem gaze circuits. In the first of two papers (Takahashi and Veale, 2023), we described the properties of gaze behavior of several species under both laboratory and natural conditions, as well as the current understanding of the brainstem and spinal cord circuits implementing gaze control in primate. In this paper, we review the parallel pathways by which sensory and task information reaches SC and how these sensory and task signals interact within SC's multilayered structure. This includes both bottom-up (world statistics) signals mediated by sensory cortex, association cortex, and subcortical structures, as well as top-down (goal and task) influences which arrive via either direct excitatory pathways from cerebral cortex, or via indirect basal ganglia relays resulting in inhibition or dis-inhibition as appropriate for alternative behaviors. Models of attention such as saliency maps serve as convenient frameworks to organize our understanding of both the separate computations of each neural pathway, as well as the interaction between the multiple parallel pathways influencing gaze. While the spatial interactions between gaze's neural pathways are relatively well understood, the temporal interactions between and within pathways will be an important area of future study, requiring both improved technical methods for measurement and improvement of our understanding of how temporal dynamics results in the observed spatiotemporal allocation of gaze. [ABSTRACT FROM AUTHOR]

Introduction: Transitions in temporal niche have occurred many times over the course of mammalian evolution. These are associated with changes in sensory stimuli available to animals, particularly with visual cues, because levels of light are so much higher during the day than at night. This relationship between temporal niche and available sensory stimuli elicits the expectation that evolutionary transitions between diurnal and nocturnal lifestyles will be accompanied by modifications of sensory systems that optimize the ability of animals to receive, process, and react to important stimuli in the environment. Methods: This study examines the influence of temporal niche on investment in sensory brain tissue of 13 rodent species (five diurnal; eight nocturnal). Animals were euthanized and the brains immediately frozen on dry ice; olfactory bulbs were subsequently dissected and weighed, and the remaining brain was weighed, sectioned, and stained. Stereo Investigator was used to calculate volumes of four sensory regions that function in processing visual (lateral geniculate nucleus, superior colliculus) and auditory (medial geniculate nucleus, inferior colliculus) information. A phylogenetic framework was used to assess the influence of temporal niche on the relative sizes of these brain structures and of olfactory bulb weights. Results: Compared to nocturnal species, diurnal species had larger visual regions, whereas nocturnal species had larger olfactory bulbs than their diurnal counterparts. Of the two auditory structures examined, one (medial geniculate nucleus) was larger in diurnal species, while the other (inferior colliculus) did not differ significantly with temporal niche. Conclusion: Our results indicate a possible indirect association between temporal niche and auditory investment and suggest probable trade-offs of investment between olfactory and visual areas of the brain, with diurnal species investing more in processing visual information and nocturnal species investing more in processing olfactory information. [ABSTRACT FROM AUTHOR]