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The age-related loss of GABA in the inferior colliculus (IC) likely plays a role in the development of age-related hearing loss. Perineuronal nets (PNs), specialized aggregates of extracellular matrix, increase with age in the IC. PNs, associated with GABAergic neurotransmission, can stabilize synapses and inhibit structural plasticity. We sought to determine whether PN expression increased on GABAergic and non-GABAergic IC cells that project to the medial geniculate body (MG). We used retrograde tract-tracing in combination with immunohistochemistry for glutamic acid decarboxylase and Wisteria floribunda agglutinin across three age groups of Fischer Brown Norway rats. Results demonstrate that PNs increase with age on lemniscal and non-lemniscal IC-MG cells, however two key differences exist. First, PNs increased on non-lemniscal IC-MG cells during middle-age, but not until old age on lemniscal IC-MG cells. Second, increases of PNs on lemniscal IC-MG cells occurred on non-GABAergic cells rather than on GABAergic cells. These results suggest that synaptic stabilization and reduced plasticity likely occur at different ages on a subset of the IC-MG pathway.

Some patients with damage to the primary visual cortex (V1) exhibit visuomotor ability, despite loss of visual awareness, a phenomenon termed “blindsight”. We review a series of studies conducted mainly in our laboratory on macaque monkeys with unilateral V1 lesioning to reveal the neural pathways underlying visuomotor transformation and the cognitive capabilities retained in blindsight. After lesioning, it takes several weeks for the recovery of visually guided saccades toward the lesion-affected visual field. In addition to the lateral geniculate nucleus, the pathway from the superior colliculus to the pulvinar participates in visuomotor processing in blindsight. At the cortical level, bilateral lateral intraparietal regions become critically involved in the saccade control. These results suggest that the visual circuits experience drastic changes while the monkey acquires blindsight. In these animals, analysis based on signal detection theory adapted to behavior in the “Yes–No” task indicates reduced sensitivity to visual targets, suggesting that visual awareness is impaired. Saccades become less accurate, decisions become less deliberate, and some forms of bottom-up attention are impaired. However, a variety of cognitive functions are retained such as saliency detection during free viewing, top–down attention, short-term spatial memory, and associative learning. These observations indicate that blindsight is not a low-level sensory-motor response, but the residual visual inputs can access these cognitive capabilities. Based on these results we suggest that the macaque model of blindsight replicates type II blindsight patients who experience some “feeling” of objects, which guides cognitive capabilities that we naïvely think are not possible without phenomenal consciousness.

The thalamus is a deep cerebral structure that is crucial for proper neurological functioning as it transmits signals from nearly all pathways in the body. Insult to the thalamus can, therefore, result in complex syndromes involving sensation, cognition, executive function, fine motor control, emotion, and arousal, to name a few. Specific territories in the thalamus that are supplied by deep cerebral arteries have been shown to correlate with clinical symptoms. The aim of this review is to enhance our understanding of the arterial anatomy of the thalamus and the complications that can arise from lesions to it by considering the functions of known thalamic nuclei supplied by each vascular territory.

Purpose Periventricular leukomalacia (PVL) is a structural loss of white matter pathways that carry visual information from the lateral geniculate bodies to the visual cortex. It is observed radiologically in patients with a history of prematurity and is associated with visual field (VF) defects and optic disc cupping. Advances in perinatal care have improved survival for premature babies, so many now present as adolescents and adults to comprehensive eye doctors who are unaware of the relationship of cupping, field defects, and prematurity and who may diagnose manifest or suspected normal tension glaucoma. We describe 2 such patients to raise awareness of this entity. Design Case series. Methods Review of clinical information of 2 patients identified during clinical practice. Charts were reviewed for gestational age, optic nerve appearance, intraocular pressure (IOP), and sequelae of prematurity. Magnetic resonance imaging (MRI), optical coherence tomography (OCT), VF, and optic disc photographs were reviewed. Results Two young patients with a history of prematurity presented with enlarged cup-to-disc ratio and normal IOP. OCT thinning was most prominent superiorly, with VF defects more notable inferior and homonymous. No progression on VF or OCT was noted in the index case over almost 4 years. Conclusions Periventricular leukomalacia should be added to the differential diagnosis of normal tension glaucoma (NTG) when there is a history of prematurity. Careful examination of the optic nerve will assist in differentiating from NTG. Specifically, horizontal cupping with minimal or no nasal displacement of vessels, and superior optic nerve thinning with inferior VF defects, suggest PVL.

The lateral geniculate nucleus (LGN) is a key thalamic nucleus in the visual system, which has an important function in relaying retinal visual input to the visual cortex. The human LGN is composed mainly of magnocellular (M) and parvocellular (P) subdivisions, each of which has different stimulus selectivity in neural response properties. Previous studies have discussed the potential relationship between LGN subdivisions and visual disorders based on psychophysical data on specific types of visual stimuli. However, these relationships remain speculative because non-invasive measurements of these subdivisions are difficult due to the small size of the LGN. Here we propose a method to identify these subdivisions by combining two structural MR measures: high-resolution proton-density weighted images and macromolecular tissue volume (MTV) maps. We defined the M and P subdivisions based on MTV fraction data and tested the validity of the definition by (1) comparing the data with that from human histological studies, (2) comparing the data with functional magnetic resonance imaging measurements on stimulus selectivity, and (3) analyzing the test-retest reliability. The findings demonstrated that the spatial organization of the M and P subdivisions was consistent across subjects and in line with LGN subdivisions observed in human histological data. Moreover, the difference in stimulus selectivity between the subdivisions identified using MTV was consistent with previous physiology literature. The definition of the subdivisions based on MTV was shown to be robust over measurements taken on different days. These results suggest that MTV mapping is a promising approach for evaluating the tissue properties of LGN subdivisions in living humans. This method potentially will enable neuroscientific and clinical hypotheses about the human LGN subdivisions to be tested.

The traditional view that visuomotor integration is a property of higher brain centres has recently been challenged by the discovery in head-fixed rodents that locomotion increases neuronal activity throughout the early visual system (including the retina). Any appreciation of the importance of this behavioural modulation of visual inputs must encompass a comprehensive understanding of the range of behaviours engaged by this mechanism. This information is unavailable from head-fixed preparations in which head and body postures are fundamentally constrained and dissociated from their natural coupling with visual experience.We addressed this deficit by recording spiking activity from the primary visual thalamus during freely moving exploration, while simultaneously applying frame-by-frame quantification of postures and movements to robust 3D reconstructions of head and body. We found that postures associated with the animal looking up/down affected activity in >50% neurons. The extent of this effect was comparable to that induced by locomotion. Moreover, the two effects were largely independent and jointly modulated neuronal activity. Thus, while most units were excited by locomotion, some expressed highest firing when the animal was looking up (“look up” neurons) while others when the animal was looking down (“look-down” neurons). These results were observed in the dark, thus representing a genuine behavioural modulation, and were amplified in a lit arena.These findings define the influence of natural exploratory behaviour on activity in the early visual system and reveal the importance of up/down postures in gating neuronal activity in the primary visual thalamus.

Task based and resting state fMRI has been widely utilized to study brain functions. As the foundation of fMRI, the underlying neural basis of the BOLD signal has been extensively studied, but the detailed mechanism remains elusive, particularly during the resting state. To examine the neurovascular coupling, it is important to simultaneously record neural and vascular signals. Here we developed a novel setup of camera based, scalable simultaneous calcium fiber photometry and fMRI in rats. Using this setup, we recorded calcium signals of superior colliculus (SC) and lateral geniculate nucleus (LGN) and fMRI simultaneously during visual stimulation and the resting state. Our results revealed robust, region-specific coupling between calcium and BOLD signals in the task state and weaker, whole brain correlation in the resting state. Interestingly, the spatial specificity of such correlation in the resting state was improved upon regression of white matter, ventricle signals and global signals in fMRI data. Overall, our results suggest differential coupling of calcium and BOLD signals for subcortical regions between evoked and resting states, and the coupling relationship in the resting state was related with resting state BOLD preprocessing strategies.

White matter abnormalities, revealed by Diffusion Tensor Imaging (DTI), are observed in patients with Alzheimer’s Disease (AD), representing neural network deficits that underlie gradual cognitive decline in patients with AD. However, how DTI changes are related to the development of Amyloid beta (Aβ) and tau pathology, two key hallmarks of AD, remains elusive. We hypothesized that tauopathy induced by Aβ could initiate an axonal degeneration process, leading to DTI-detectable white matter abnormalities. We utilized the visual system of the transgenic p301L tau mice as a model system. Aβ was injected in Lateral Geniculate Nucleus (LGN), where the Retinal Ganglion Cell (RGC) axons terminate, and longitudinal DTI was conducted to detect changes in the optic tract (OT, containing the distal segment of RGC axons) and optic nerve (ON, containing the proximal segment of RGC axons). Our results showed early DTI changes in OT (significant 13.2% reduction in axial diffusion, AxD vs. vehicle controls) followed by later significant alterations in ON AxD and fractional anisotropy, FA. Histology data revealed loss of synapses, RGC axons and cell bodies resulting from the Aβ injection. We further tested whether microtubule-stabilizing compound Epothilone D (EpoD) could ameliorate the damage. EpoD co-treatment with Aβ was sufficient to prevent Aβ-induced axon and cell loss. Using an acute injection paradigm, our data suggest that EpoD may mediate its protective effect by blocking localized, acute Aβ-induced tau phosphorylation. This study demonstrates white matter disruption resulting from localized Aβ, the importance of tau pathology induction to changes in white matter connectivity, and the use of EpoD as a potential therapeutic avenue to block axon loss during disease.

To study the DNA damage and repair methods of visual central neurons in a glaucoma model, a rhesus monkey chronic glaucoma model was established by laser induction, and changes in intraocular pressure (IOP), the optic cup fundus, the thickness of the retinal nerve fiber layer and the diameter of the optic nerve were evaluated. After a sufficient period of time, the model was euthanized, and the lateral geniculate body, primary visual cortex (V1 region) and secondary visual cortex (V2 region) were removed. Through immunofluorescence, ELISA and western blotting assays, the expressions of 8-hydroxyguanosine (8-OHG), a biomarker of oxidative stress, and γH2AX, a marker of DNA double-strand breaks, in the neurons of the LGN, V1 and V2 in the glaucoma model were higher than those of the control group (P 0.05). The expression of key DNA repair proteins Ku80, Mre11, PCNA, DNA ligase IV and APE1 antibodies in the LGN, V1 and V2 of the glaucoma model was higher than that of the control group (P 0.05), and in the positive TUNEL cells, the levels of cleaved caspase 3, Beclin 1 and LC3B-II/LC3B-I were significantly increased in the LGN of the glaucoma model (P 0.05), but there was no significant positive expression in the V1 and V2 regions of the glaucoma model compared with the normal control group (P 0.05). Transmission electron microscopy also showed that apoptotic bodies and autolysosomes (changes in neuronal apoptosis and autophagy activation) appeared in some neurons of the LGN in glaucoma, but there were no significant abnormal changes in the V1 and V2 regions of glaucoma or in any specimens in the normal group. In terms of neuron counting, the number of neurons in the LGN of the glaucoma model was lower than that in the normal control group (P 0.05), but there was no significant difference in the number of neurons in the V1 and V2 regions between the two groups (P 0.05). Similarly, the expression of glial cells in the LGN, V1 and V2 of the glaucoma model was higher than that in the control group (P 0.05). Therefore, the results showed that DNA oxidative damage and various repair processes occurred in neurons of the LGN, V1 and V2 of the glaucoma model, and finally, LGN neurons died in the glaucoma model.

Light is a powerful modulator of non-visual functions. Although accumulating evidence suggests an antinociceptive effect of bright light treatment, the precise circuits that mediate the effects of light on nocifensive behaviors remain unclear. Here, we show that bright light treatment suppresses mouse nocifensive behaviors through a visual circuit related to the lateral and ventral lateral parts of the periaqueductal gray area (l/vlPAG). Specifically, a subset of retinal ganglion cells (RGCs) innervates GABAergic neurons in the ventral lateral geniculate nucleus and intergeniculate leaflet (vLGN/IGL), which in turn inhibit GABAergic neurons in the l/vlPAG. The activation of vLGN/IGL-projecting RGCs, activation of l/vlPAG-projecting vLGN/IGL neurons, or inhibition of postsynaptic l/vlPAG neurons is sufficient to suppress nocifensive behaviors. Importantly, we demonstrate that the antinociceptive effects of bright light treatment are dependent on the activation of the retina-vLGN/IGL-l/vlPAG pathway. Together, our results delineate an l/vlPAG-related visual circuit underlying the antinociceptive effects of bright light treatment.

Background Given energy metabolism, visual information degradation plays an essential role in the retina- lateral geniculate nucleus (LGN)-primary visual cortex (V1)-secondary visual cortex (V2) pathway, and is a pivotal issue for visual information processing. Degradation helps the visual nervous system conserve brain energy and efficiently perceive the real world even though a small fraction of visual information reaches the early visual areas. The coding of contour features (edge and corner) is achieved in the retina-LGN-V1-V2 pathway. Based on the above, we proposed a contour detection model based on degradation (CDMD). New method Inspired by pupillary light reflex regulation, we took into consideration the novel approach of the hue-saturation-value (HSV) module for color encoding to meet the subtle chromaticity change rather than using the traditional red-green-blue (RGB) module, following the mechanisms of dark (DA) and light (LA) adaptation processes in photoreceptors. Meanwhile, the degradation mechanism was introduced as a novel strategy focusing only on the essential information to detect contour features, mimicking contour detection by visual perception under the restriction of axons in each optic nerve biologically. Ultimately, we employed the feedback mechanism achieving the optimal HSV value for each pixel of the experimental datasets. Results We used the publicly available Berkeley Segmentation Data Set 500 (BSDS500) to assess the effectiveness of our CDMD model, introduced the F-measure to evaluate the results. The F-measure score was 0.65, achieved by our model. Moreover, CDMD with HSV has a better sensitivity for subtle chromaticity changes than CDMD with RGB. Comparison with existing methods Experimental results demonstrated that our CDMD model, which functions close to the real visual system, achieved a more competitive performance with low computational cost than some state-of-art non-deep-learning and biologically inspired models. Compared with deep-learning-based algorithms, our model contains fewer parameters and computation time, does not require additional visual features, as well as an extra training process. Conclusions Our proposed CDMD model is a novel approach for contour detection, which mimics the cognitive function of contour detection in early visual areas, and realizes a competitive performance in image processing. It contributes to bridging the gap between the biological visual system and computer vision.

Recent developments in fMRI acquisition techniques now enable fast sampling with whole-brain coverage, suggesting fMRI can be used to track changes in neural activity at increasingly rapid timescales. When images are acquired at fast rates, the limiting factor for fMRI temporal resolution is the speed of the hemodynamic response. Given that HRFs may vary substantially in subcortical structures, characterizing the speed of subcortical hemodynamic responses, and how the hemodynamic response shape changes with stimulus duration (i.e. the hemodynamic nonlinearity), is needed for designing and interpreting fast fMRI studies of these regions. We studied the temporal properties and nonlinearities of the hemodynamic response function (HRF) across the human subcortical visual system, imaging superior colliculus (SC), lateral geniculate nucleus of the thalamus (LGN) and primary visual cortex (V1) with high spatiotemporal resolution 7 Tesla fMRI. By presenting stimuli of varying durations, we mapped the timing and nonlinearity of hemodynamic responses in these structures at high spatiotemporal resolution. We found that the hemodynamic response is consistently faster and narrower in subcortical structures than in cortex. However, the nonlinearity in LGN is similar to that in cortex, with shorter duration stimuli eliciting larger and faster responses than would have been predicted by a linear model. Using oscillatory visual stimuli, we tested the frequency response in LGN and found that its BOLD response tracked high-frequency (0.5 Hz) oscillations. The LGN response magnitudes were comparable to V1, allowing oscillatory BOLD signals to be detected in LGN despite the small size of this structure. These results suggest that the increase in the speed and amplitude of the hemodynamic response when neural activity is brief may be the key physiological driver of fast fMRI signals, enabling detection of high-frequency oscillations with fMRI. We conclude that subcortical visual structures exhibit fast and nonlinear hemodynamic responses, and that these dynamics enable detection of fast BOLD signals even within small deep brain structures when imaging is performed at ultra-high field.

Multiple sclerosis is characterized by intermingled episodes of de- and remyelination and the occurrence of white- and grey-matter damage. To mimic the randomly distributed pathophysiological brain lesions observed in MS, we assessed the impact of focal white and grey matter demyelination on thalamic function by directing targeted lysolecithin-induced lesions to the capsula interna (CI), the auditory cortex (A1), or the ventral medial geniculate nucleus (vMGN) in mice. Pathophysiological consequences were compared with those of cuprizone treatment at different stages of demyelination and remyelination. Combining single unit recordings and auditory stimulation in freely behaving mice revealed changes in auditory response profile and electrical activity pattern in the thalamus, depending on the region of the initial insult and the state of remyelination. Cuprizone-induced general demyelination significantly diminished vMGN neuronal activity and frequency-specific responses. Targeted lysolecithin-induced lesions directed either to A1 or to vMGN revealed a permanent impairment of frequency-specific responses, an increase in latency of auditory responses and a reduction in occurrence of burst firing in vMGN neurons. These findings indicate that demyelination of grey matter areas in the thalamocortical system permanently affects vMGN frequency specificity and the prevalence of bursting in the auditory thalamus.

The "blue-on" and "blue-off" receptive fields in retina and dorsal lateral geniculate nucleus (LGN) of diurnal primates combine signals from short-wavelength sensitive (S) cone photoreceptors with signals from medium/long wavelength sensitive (ML) photoreceptors. Three questions about this combination remain unresolved. Firstly, is the combination of S and ML signals in these cells linear or non-linear? Secondly, how does the timing of S and ML inputs to these cells influence their responses? Thirdly, is there spatial antagonism within S and ML subunits of the receptive field of these cells? We measured contrast sensitivity and spatial frequency tuning for four types of drifting sine gratings: S cone isolating, ML cone isolating, achromatic (S + ML), and counterphase chromatic (S - ML), in extracellular recordings from LGN of marmoset monkeys. We found that responses to stimuli which modulate both S and ML cones are well predicted by a linear sum of S and ML signals, followed by a saturating contrast-response relation. Differences in sensitivity and timing (i.e. vector combination) between S and ML inputs are needed to explain the amplitude and phase of responses to achromatic (S + ML) and counterphase chromatic (S - ML) stimuli. Best-fit spatial receptive fields for S and/or ML subunits in most cells (>80%) required antagonistic surrounds, usually in the S subunit. The surrounds were however generally weak and had little influence on spatial tuning. The sensitivity and size of S and ML subunits were correlated on a cell-by-cell basis, adding to evidence that blue-on and blue-off receptive fields are specialised to signal chromatic but not spatial contrast.

Synaptic short-term plasticity (STP) regulates synaptic transmission in an activity-dependent manner and thereby has important roles in the signal processing in the brain. In some synapses, a presynaptic train of action potentials elicits post-synaptic potentials that gradually increase during the train (facilitation), but in other synapses, these potentials gradually decrease (depression). We studied STP in neurons in the visual thalamic relay, the dorsal lateral geniculate nucleus (dLGN). The dLGN contains two types of neurons: excitatory thalamocortical (TC) neurons, which transfer signals from retinal afferents to visual cortex, and local inhibitory interneurons, which form an inhibitory feedforward loop that regulates the thalamocortical signal transmission. The overall STP in the retino-thalamic relay is short-term depression, but the distinct kind and characteristics of the plasticity at the different types of synapses are unknown. We studied STP in the excitatory responses of interneurons to stimulation of retinal afferents, in the inhibitory responses of TC neurons to stimulation of afferents from interneurons, and in the disynaptic inhibitory responses of TC neurons to stimulation of retinal afferents. Moreover, we studied STP at the direct excitatory input to TC neurons from retinal afferents. The STP at all types of the synapses showed short-term depression. This depression can accentuate rapid changes in the stream of signals and thereby promote detectability of significant features in the sensory input. In vision, detection of edges and contours is essential for object perception, and the synaptic short-term depression in the early visual pathway provides important contributions to this detection process.

Genetically modified mouse strains that express Cre-recombinase in specific neuronal sub-populations have become widely used tools for investigating neuronal function. The Ntsr1-Cre GN220 mouse expresses this enzyme in corticothalamic neurons in layer 6 of cerebral cortex. We observed that about 7% of Cre-expressing cells in the primary visual cortex are found within the white matter bordering layer 6. By using the immunohistochemical marker for layer 6 neurons, Forkhead box protein 2 (FoxP2), and fluorescently conjugated latex beads injected into the dorsal lateral geniculate nucleus, we show that about half of these cells are similar to and could belong to the layer 6 corticothalamic neuron population. The other half seems to be a distinct white matter (WM) neuron sub-population that we estimate to constitute 2-4% of the total cortical Cre-expressing population. Staining for the neuronal marker Neuronal nuclei (NeuN) revealed that about 15-40% of WM neurons are Cre-expressing. Thus, the potential contribution from WM neurons needs to be considered when interpreting the results from experiments using the Ntsr1-Cre GN220 mouse for investigating corticothalamic neuronal function.

Simple cells in the cat primary visual cortex usually have elongated receptive fields (RFs), and their orientation selectivity can be largely predicted by their RFs. As to the relay cells in cats' lateral geniculate nucleus (LGN), they also have weak but significant orientation bias (OB). It is thus of interest to investigate the fine spatiotemporal receptive field (STRF) properties in LGN, compare them with the dynamics of orientation tuning, and examine the dynamic relationship between STRF and orientation sensitivity in LGN. We mapped the STRFs of the LGN neurons in cats with white noise and characterized the dynamics of the orientation tuning by flashing gratings. We found that most of the LGN neurons showed elongated RFs and that the elongation axes were consistent with the preferred orientations. STRFs and the dynamics of orientation tuning were closely correlated temporally: the elongation of RFs and OB emerged, peaked and decayed at the same pace, with unchanged elongation axis of RF and preferred orientation but consistently changing aspect ratio of RF and OB strength across time. Importantly, the above consistency between RF and orientation tuning was not influenced by the ablation of the primary visual cortex. Furthermore, biased orientation tuning emerged 20-30 ms earlier than those in the primary visual cortex. These data demonstrated that similar to the primary visual cortex, the orientation sensitivity was closely reflected by the RF properties in LGN. However, the elongated RF and OB in LGN did not originate from the primary visual cortex feedback.

Perinatal inflammatory insult in preterm babies is associated with vision impairment, but the underlying cellular mechanism is still unknown. In this study, we set out to explore whether systemic inflammatory stress affects the development of retinal ganglion cells (RGCs). Neonatal inflammation was induced by single and systemic injection of lipopolysaccharide (LPS, 1 mg/kg) at postnatal day 4 (P4). Morphological changes of RGCs were investigated by using 3D neuron reconstruction technique in Thy-1 YFPH transgenic mice at P21, of which a fraction of RGCs selectively expresses the yellow fluorescent protein (YFP). Three types (Type I, II, III) of RGCs were distinguished and classified according to the characteristic features in their dendritic field area and dendrite density. Neonatal exposure to LPS did not alter the composition of the three RGC types but induced a reorganization of dendritic architecture in the RGC Type I and II (but not Type III). The average diameter, surface area and volume of dendrites in both RGC Type I and II were increased after systemic inflammation compared with those in the control group. However, soma sizes of all three RGC types were not affected by neonatal inflammation. Meanwhile, using anterograde labeling of the retinal cells, we found that neonatal exposure to LPS also did not affect the pattern of RGC projections in the dorsal lateral geniculate nucleus of the thalamus (dLGN). These results indicate that RGC dendrite reorganization induced by neonatal inflammation may contribute to the retinal cell dysfunctions associated with systemic inflammation in premature babies.

Developmental refinement of neuronal connectivity is crucial for proper brain function. In the early phase of development, input fibers arrive at their target areas guided by specific molecular cues and form abundant immature synapses. Then, functionally important synapses are preserved and strengthened by neural activity while unnecessary synapses are eliminated. Afferent synapses in the sensory thalamus, such as from retina to lateral geniculate nucleus, and climbing fiber (CF)-Purkinje cell (PC) synapses in the cerebellum are valuable models for studying this developmental refinement of synaptic connectivity because only a limited number of input fibers innervate a given postsynaptic thalamocortical (TC) neuron or PC. The metabotropic glutamate receptor subtype 1 (mGluR1) is required for the refinement of both afferent-TC neuron and CF-PC synapses. However, mGluR1 functions differently at these synapses. While mGluR1 is critical for elimination of surplus CF-PC synapses in the cerebellum, retinogeniculate synapses require mGluR1 for maintenance of mature connectivity.

Nitric oxide (NO) is a highly soluble and membrane-permeable neurotransmitter, so it does not need to be packed in vesicles or have a membrane receptor. In the nervous system, NO is synthesized by the neuronal form of the nitric oxide synthase (NOS) enzyme and has been considered as a local neurotransmitter. NOS distribution is widespread in the nervous system of various vertebrate species, which may explain its participation in many functions such as memory, blood pressure regulation and sexual behavior. Here we used immunohistochemistry against NOS and NADPH diaphorase histochemistry to map the distribution of NO in the diencephalon of the rock cavy (Kerodon rupestris), a rodent endemic to the Brazilian Northeast. Rock cavy has crepuscular habits and is adapted to ecological conditions such as heat and scarcity of water and food. This study found that NOS distribution was more concentrated in the hypothalamus of this animal. Among the hypothalamic nuclei, the median preoptic, supraoptic, paraventricular nucleus of the hypothalamus, ventromedial nucleus of the hypothalamus, ventral and dorsal premammillary nucleus, supramammillary nucleus, lateral mammillary nucleus and dorsal hypothalamic nucleus had the largest collections of NOS immunoreactive (NOS-ir) neurons. Some nuclei of the thalamus and epithalamus such as the paraventricular nucleus of the thalamus, the ventral lateral geniculate nucleus, the medial geniculate nucleus and the lateral habenula showed NOS-ir neurons. This distribution is similar to that described in other rodents, indicating that NO also has an important role in rock cavy's physiology.

Summary Higher-order (HO) thalamic nuclei interact extensively and reciprocally with the cerebral cortex. These corticothalamic (CT) interactions are thought to be important for sensation and perception, attention, and many other important brain functions. CT projections to HO thalamic nuclei, such as the visual pulvinar, originate from two different excitatory populations in cortical layers 5 and 6, whereas first-order nuclei (such as the dorsolateral geniculate nucleus; dLGN) only receive layer 6 CT input. It has been proposed that these layer 5 and layer 6 CT pathways have different functional influences on the HO thalamus, but this has never been directly tested. By optogenetically inactivating different CT populations in the primary visual cortex (V1) and recording single-unit activity from V1, dLGN, and pulvinar of awake mice, we demonstrate that layer 5, but not layer 6, CT projections drive visual responses in the pulvinar, even while both pathways provide retinotopic, baseline excitation to their thalamic targets. Inactivating the superior colliculus also suppressed visual responses in the same subregion of the pulvinar, demonstrating that cortical layer 5 and subcortical inputs both contribute to HO visual thalamic activity—even at the level of putative single neurons. Altogether, these results indicate a functional division of “driver” and “modulator” CT pathways from V1 to the visual thalamus in vivo.

This study assessed the role of caffeine (adenosine receptor antagonist) in the Lateral geniculate body as well as the primary visual cortex of hyaluronic acid model of glaucomatous rats. Twenty (20) male Long evans rats were randomly divided into four groups with five animals each. This research confirmed that hyaluronic acid (HA) significantly induces elevated intraocular pressure from 18 to 35 mmHg and caffeine had no effect on its reduction to palliate visual impairment; There were a significant increase in the lipid peroxidation and conversely decrease in superoxide level with HA which were attenuated by caffeine. Although, caffeine showed a capability of ameliorating the histopathological changes induced by HA in terms of maintenance of a viable neuronal cell count and significant reduction of tumour necrosis factor-α immune positive cells in the LGB and visual cortex. These findings suggest that caffeine was unable to lower the intraocular pressure after hyaluronic acid exposure but has the ability to restore the antioxidant imbalance via mitigating pro-oxidant mediators and abrogate neurodegeneration.

Heightened fear responding is characteristic of fear- and anxiety-related disorders, including post-traumatic stress disorder. Neural plasticity in the amygdala is essential for both initial fear learning and fear expression, and strengthening of synaptic connections between the medial geniculate nucleus (MgN) and amygdala is critical for auditory fear learning. However, very little is known about what happens in the MgN-amygdala pathway during fear recall and extinction, in which conditional fear decreases with repeated presentations of the auditory stimulus alone. In the present study, we found that optogenetic inhibition of activity in the MgN-amygdala pathway during fear retrieval and extinction reduced expression of conditional fear. While this effect persisted for at least two weeks following pathway inhibition, it was specific to the context in which optogenetic inhibition occurred, linking MgN-BLA inhibition to facilitation of extinction-like processes. Reduced fear expression through inhibition of the MgN-amygdala pathway was further characterized by similar synaptic expression of GluA1 and GluA2 AMPA receptor subunits compared to what was seen in controls. Inhibition also decreased CREB phosphorylation in the amygdala, similar to what has been reported following auditory fear extinction. We then demonstrated that this effect was reduced by inhibition of GluN2B-containing NMDA receptors. These results demonstrate a new and important role for the MgN-amygdala pathway in extinction-like processes, and show that suppressing activity in this pathway results in a persistent decrease in fear behavior.

Color vision, originating with opponent processing of spectrally distinct photoreceptor signals, plays important roles in animal behavior.1-4 Surprisingly, however, comparatively little is understood about color processing in the brain, including in widely used laboratory mammals such as mice. The retinal gradient in S- and M-cone opsin (co-)expression has traditionally been considered an impediment to mouse color vision.5-8 However, recent data indicate that mice exhibit robust chromatic discrimination within the central-upper visual field.9 Retinal color opponency has been reported to emerge from superimposing inhibitory surround receptive fields on the cone opsin expression gradient, and by introducing opponent rod signals in retinal regions with sparse M-cone opsin expression.10-13 The relative importance of these proposed mechanisms in determining the properties of neurons at higher visual processing stages remains unknown. We address these questions using multielectrode recordings from the lateral geniculate nucleus (LGN) in mice with altered M-cone spectral sensitivity (Opn1mwR) and multispectral stimuli that allow selective modulation of signaling by individual opsin classes. Remarkably, we find many (∼25%) LGN cells are color opponent, that such cells are localized to a distinct medial LGN zone and that their properties cannot simply be explained by the proposed retinal opponent mechanisms. Opponent responses in LGN can be driven solely by cones, independent of cone-opsin expression gradients and rod input, with many cells exhibiting spatially congruent antagonistic receptive fields. Our data therefore suggest previously unidentified mechanisms may support extensive and sophisticated color processing in the mouse LGN.

Functional magnetic resonance imaging (fMRI) based on the blood oxygenation level-dependent (BOLD) contrast has become an indispensable tool in neuroscience. However, the BOLD signal is nonlocal, lacking quantitative measurement of oxygenation fluctuation. This preclinical study aimed to introduced functional quantitative susceptibility mapping (fQSM) to complement BOLD-fMRI to quantitatively assess the local susceptibility and venous oxygen saturation (SvO2). Rats were subjected to a 5 Hz flashing light and the different inhaled oxygenation levels (30% and 100%) were used to observe the venous susceptibility to quantify SvO2. Phase information was extracted to produce QSM, and the activation responses of magnitude (conventional BOLD) and the QSM time-series were analyzed. During light stimulation, the susceptibility change of fQSM was four times larger than the BOLD signal change in both inhalation oxygenation conditions. Moreover, the responses in the fQSM map were more restricted to the visual pathway, such as the lateral geniculate nucleus and superior colliculus, compared with the relatively diffuse distributions in the BOLD map. Also, the calibrated SvO2 was approximately 84% (88%) when the task was on, 83% (87%) when the task was off during 30% (and during 100%) oxygen inhalation. This is the first fQSM study in a small animal model and increases our understanding of fQSM in the brains of small animals. This study demonstrated the feasibility, sensitivity, and specificity of fQSM using light stimulus, as fQSM provides quantitative clues as well as localized information, complementing the defects of BOLD-fMRI. In addition to neural activity, fQSM also assesses SvO2 as supplementary information while BOLD-fMRI dose not. Accordingly, the fQSM technique could be a useful quantitative tool for functional studies, such as longitudinal follow up of neurodegenerative diseases, functional recovery after brain surgery, and negative BOLD studies.

Background Intraventricular meningiomas comprise 0.5%–3% of intracranial meningiomas. They often cause obstructive hydrocephalus and commonly are treated with surgical resection or stereotactic radiosurgery. Objective To describe the surgical approaches and resection techniques needed to approach intraventricular tumors while highlighting the eloquent anatomy and blood supply surrounding the ventricular system to avoid neurological injury. Methods Two cases of left atrial intraventricular meningiomas that were complicated by postoperative lateral geniculate nucleus ischemia and resultant temporary contralateral quadrantanopia are described. The safe surgical approaches to the atrium of lateral ventricles as well as the anatomy and blood supply to the lateral geniculate nucleus and optic radiation are discussed and illustrated. Results In both cases, the patients had complete resection of their tumors. They both ultimately made a good recovery after transient visual deficits. These cases provide useful demonstrations of eloquent anatomy of the ventricular walls and visual pathway anatomy. Conclusions Care must be taken to avoid visual pathways along the lateral ventricle wall and the nearby arterial supply of the lateral geniculate nucleus from the choroidal arteries when resecting intraventricular tumors.

Cellular luminescence is the emission of photons by living cells due to various biophysical and biochemical processes, mostly associated with cellular metabolism. In this review paper we summarize today's understanding of four luminescence-dependent phenomena in the eye, i.e., phosphenes, retinal discrete dark noise, negative afterimages and the development of retinogeniculate projections in the brain. We review the phenomena above in the context of knowledge gained from experimental and theoretical works. Finally, we discuss this knowledge in terms of its physiological significance.

The lateral geniculate nucleus (LGN) has often been treated in the past as a linear filter that adds little to retinal processing of visual inputs. Here we review anatomical, neurophysiological, brain imaging, and modeling studies that have in recent years built up a much more complex view of LGN . These include effects related to nonlinear dendritic processing, cortical feedback, synchrony and oscillations across LGN populations, as well as involvement of LGN in higher level cognitive processing. Although recent studies have provided valuable insights into early visual processing including the role of LGN, a unified model of LGN responses to real-world objects has not yet been developed. In the light of recent data, we suggest that the role of LGN deserves more careful consideration in developing models of high-level visual processing.

This study was designed to perform psychophysical assessment of koniocellular pathway in patients with schizophrenia versus healthy controls. A total of 26 patients diagnosed with schizophrenia and 15 healthy controls were included. Snellen Visual Acuity Chart scores and Short Wavelength Automated Perimetry (SWAP) visual field testing including global visual field indices [mean deviation (MD), pattern standard deviation (PSD), test time (min)], reliability parameters [false negative responses (%), false positive responses (%) and fixed losses (%)] and average threshold sensitivity [central (parafovea), peripheral area, and four quadrants] were recorded in both groups. Significantly lower MD scores, higher PSD scores and lower average threshold sensitivity at each location across the visual field were noted in schizophrenia relative to control group. In conclusion, our findings revealed a deficit in koniocellular pathway with impaired SWAP global indices and lower threshold sensitivity at each location across the visual field among chronic schizophrenic patients as compared with control subjects. Our findings emphasize potential application of SWAP outside its original intended purpose as a glaucoma test, to provide deeper understanding of the specific contribution of lateral geniculate nucleus to the visual and cognitive disturbances of schizophrenia.

Summary The brain is continuously modified by perceptual experience throughout life. Perceptual learning, which refers to the long-term performance improvement resulting from practice, has been widely used as a paradigm to study experience-dependent brain plasticity in adults [1, 2]. In the visual system, adult plasticity is largely believed to be restricted to the cortex, with subcortical structures losing their capacity for change after a critical period of development [3, 4]. Although various cortical mechanisms have been shown to mediate visual perceptual learning [5–12], there has been no reported investigation of perceptual learning in subcortical nuclei. Here, human subjects were trained on a contrast detection task for 30 days, leading to a significant contrast sensitivity improvement that was specific to the trained eye and the trained visual hemifield. Training also resulted in an eye- and hemifield-specific fMRI signal increase to low-contrast patterns in the magnocellular layers of the lateral geniculate nucleus (LGN), even when subjects did not pay attention to the patterns. Such an increase was absent in the parvocellular layers of the LGN and visual cortical areas. Furthermore, the behavioral benefit significantly correlated with the neural enhancement. These findings suggest that LGN signals can be amplified by training to detect faint patterns. Neural plasticity induced by perceptual learning in human adults might not be confined to the cortical level but might occur as early as at the thalamic level.

How many thalamic neurons converge onto a cortical cell? This is an important question because the organization of thalamocortical projections can influence the cortical architecture [1, 2]. Here we estimate the degree of thalamocortical convergence in primary visual cortex by taking advantage of the cortical expansion – neurons within a restricted volume in primary visual cortex have overlapping receptive fields driven by a smaller set of inputs from the lateral geniculate nucleus [3–5]. Under these conditions, the measurements of cortical receptive fields in a population can be used to infer the receptive fields of their geniculate inputs and the weights of their projections using non-negative matrix factorization [6]. The analysis reveals sparse connectivity [7], where a handful (~2 − 6) of thalamic inputs account for 90% of the total synaptic weight to a cortical neuron. Together with previous findings [8] these results paint a picture consistent with the idea that convergence of a few inputs partly determine the retinotopy and tuning properties of cortical cells [8–13].

Backgrounds Optic radiation protection is crucial in the basal temporal approach to the mesial temporal lobe. Clear description of the optic radiation in the basal brain surface is lacking. Our aim is to describe the anatomy of optic radiation in the basal cerebral surface and define safety zone of basal temporal approach avoiding of optic radiation injury. Methods Five brain specimens (10 hemispheres) were dissected using Klingler method to observe the course of the optic radiation. Diffusion tensor imaging data of 25 volunteers were used to verify the fiber dissection results. The relationship of the optic radiation to nearby structures were illustrated and measured. Results The optic radiation bends from the lateral wall of the lateral ventricle to its bottom at a basal turning point of optic radiation (bTPOR). The bTPOR is at the plane crossing the center point of the splenium of corpus callosum. MRI measurements showed no significant difference in the distance from the center of the splenium of corpus callosum and the bTPOR to the occipital pole (59.46 ± 4.338 mm vs 59.54 ± 3.805 mm, p = 0.95). Anterior to bTPOR, no optic radiation fibers were found at the basal brain surface. Conclusions The bTPOR was found as a landmark of the optic radiation in the cerebral basal surface. With neuronavigation, the splenium of corpus callosum can be a landmark of the bTPOR. By approaching mesial temporal lesions using the basal temporal approach anterior to bTPOR, optic radiation injury can be prevented.

The rat has long been considered an important model system for studying neural mechanisms of auditory perception and learning, and particularly mechanisms involving auditory thalamo-cortical processing. However, the functional topography of the auditory thalamus, or medial geniculate body (MGB) has not yet been fully characterized in the rat, and the anatomically-defined features of field-specific, layer-specific and tonotopic thalamo-cortical projections have never been confirmed electrophysiologically. In the present study, we have established a novel technique for recording simultaneously from a surface microelectrode array on the auditory cortex, and a depth electrode array across auditory cortical layers and within the MGB, and characterized the rat MGB and thalamo-cortical projections under isoflurane anesthesia. We revealed that the ventral division of the MGB (MGv) exhibited a low–high–low CF gradient and long-short-long latency gradient along the dorsolateral-to-ventromedial axis, suggesting that the rat MGv is divided into two subdivisions. We also demonstrated that microstimulation in the MGv elicited cortical activation in layer-specific, region-specific and tonotopically organized manners. To our knowledge, the present study has provided the first and most compelling electrophysiological confirmation of the anatomical organization of the primary thalamo-cortical pathway in the rat, setting the groundwork for further investigation.

Neural circuits formed during postnatal development have to be maintained stably thereafter, but their mechanisms remain largely unknown. Here we report that the metabotropic glutamate receptor subtype 1 (mGluR1) is essential for the maintenance of mature synaptic connectivity in the dorsal lateral geniculate nucleus (dLGN). In mGluR1 knockout (mGluR1-KO) mice, strengthening and elimination at retinogeniculate synapses occurred normally until around postnatal day 20 (P20). However, during the subsequent visual-experience-dependent maintenance phase, weak retinogeniculate synapses were newly recruited. These changes were similar to those of wild-type (WT) mice that underwent visual deprivation or inactivation of mGluR1 in the dLGN from P21. Importantly, visual deprivation was ineffective in mGluR1-KO mice, and the changes induced by visual deprivation in WT mice were rescued by pharmacological activation of mGluR1 in the dLGN. These results demonstrate that mGluR1 is crucial for the visual-experience-dependent maintenance of mature synaptic connectivity in the dLGN.

We use an fMRI adaptation paradigm to explore the selectivity of human responses in the lateral geniculate nucleus (LGN) and superior colliculus (SC) to red–green color and achromatic contrast. We measured responses to red–green (RG) and achromatic (ACH) high contrast sinewave counter-phasing rings with and without adaptation, within a block design. The signal for the RG test stimulus was reduced following both RG and ACH adaptation, whereas the signal for the ACH test was unaffected by either adaptor. These results provide compelling evidence that the human LGN and SC have significant capacity for color adaptation. Since in the LGN red–green responses are mediated by P cells, these findings are in contrast to earlier neurophysiological data from non-human primates that have shown weak or no contrast adaptation in the P pathway. Cross-adaptation of the red–green color response by achromatic contrast suggests unselective response adaptation and points to a dual role for P cells in responding to both color and achromatic contrast. We further show that subcortical adaptation is not restricted to the geniculostriate system, but is also present in the superior colliculus (SC), an oculomotor region that until recently, has been thought to be color-blind. Our data show that the human SC not only responds to red–green color contrast, but like the LGN, shows reliable but unselective adaptation.

According to the prevailing view of neural development, sensory pathways develop sequentially in a feedforward manner, whereby each local microcircuit refines and stabilizes before directing the wiring of its downstream target. In the visual system, retinal circuits are thought to mature first and direct refinement in the thalamus, after which cortical circuits refine with experience-dependent plasticity. In contrast, we now show that feedback from cortex to thalamus critically regulates refinement of the retinogeniculate projection during a discrete window in development, beginning at postnatal day 20 in mice. Disrupting cortical activity during this window, pharmacologically or chemogenetically, increases the number of retinal ganglion cells innervating each thalamic relay neuron. These results suggest that primary sensory structures develop through the concurrent and interdependent remodeling of subcortical and cortical circuits in response to sensory experience, rather than through a simple feedforward process. Our findings also highlight an unexpected function for the corticothalamic projection.

In an attempt to chart parallel sensory streams passing through the visual thalamus, we acquired a 100-trillion-voxel electron microscopy (EM) dataset and identified cohorts of retinal ganglion cell axons (RGCs) that innervated each of a diverse group of postsynaptic thalamocortical neurons (TCs). Tracing branches of these axons revealed the set of TCs innervated by each RGC cohort. Instead of finding separate sensory pathways, we found a single large network that could not be easily subdivided because individual RGCs innervated different kinds of TCs and different kinds of RGCs co-innervated individual TCs. We did find conspicuous network subdivisions organized on the basis of dendritic rather than neuronal properties. This work argues that, in the thalamus, neural circuits are not based on a canonical set of connections between intrinsically different neuronal types but, rather, may arise by experience-based mixing of different kinds of inputs onto individual postsynaptic cells.

For the processing of target-distance information, delay-tuned auditory neurons of the mustached bat show facilitative responses to a combination of signal elements of a biosonar pulse-echo pair with a specific echo delay. They are initially produced in the inferior colliculus by facilitative responses based on the coincidence of the rebound response following glycinergic inhibition to the first harmonic of the pulse and a short-latency response to the 2nd-4th harmonics of its echo. Here, we report that further facilitative responses to pulse-echo pairs of thalamic delay-tuned neurons are mediated by glutamate receptors (NMDA and non-NMDA receptors), and that GABAergic inhibition shortens the duration of facilitative responses mediated by NMDA-receptors, without changing the delay tuning of thalamic delay-tuned neurons. Different from collicular delay-tuned neurons, thalamic ones respond much more to pulse-echo pairs than individual signal elements. The neural mechanisms involved in shaping thalamic delay-tuning support a model of hierarchical signal processing in the auditory system.

Brainstem lesions causing peduncular hallucinosis (PH) produce vivid visual hallucinations occasionally accompanied by sleep disorders. Overlapping brainstem regions modulate visual pathways and REM sleep functions via gating of thalamocortical networks. A 66-year-old man with paroxysmal atrial fibrillation developed abrupt–onset complex visual hallucinations with preserved insight and violent dream enactment behavior. Brain MRI showed restricted diffusion in the left rostrodorsal pons suggestive of an acute ischemic stroke. REM sleep behavior disorder (RBD) was diagnosed on polysomnography. We investigated the integrity of ponto-geniculate-occipital circuits with seed-based resting-state functional connectivity MRI (rs-fcMRI) in this patient compared to 46 controls. Rs-fcMRI revealed significantly reduced functional connectivity between the lesion and lateral geniculate nuclei (LGN), and between LGN and visual association cortex compared to controls. Conversely, functional connectivity between brainstem and visual association cortex, and between visual association cortex and prefrontal cortex (PFC) was significantly increased in the patient. Focal damage to the rostrodorsal pons is sufficient to cause RBD and PH in humans, suggesting an overlapping mechanism in both syndromes. This lesion produced a pattern of altered functional connectivity consistent with disrupted visual cortex connectivity via de-afferentation of thalamocortical pathways.

Summary In the mammalian visual system, information from the retina streams into parallel bottom-up pathways. It remains unclear how these pathways interact to contribute to contextual modulation of visual cortical processing. By optogenetic inactivation and activation of mouse lateral posterior nucleus (LP) of thalamus, a homolog of pulvinar, or its projection to primary visual cortex (V1), we found that LP contributes to surround suppression of layer (L) 2/3 responses in V1 by driving L1 inhibitory neurons. This results in subtractive suppression of visual responses and an overall enhancement of orientation, direction, spatial, and size selectivity. Neurons in V1-projecting LP regions receive bottom-up input from the superior colliculus (SC) and respond preferably to non-patterned visual noise. The noise-dependent LP activity allows V1 to “cancel” noise effects and maintain its orientation selectivity under varying noise background. Thus, the retina-SC-LP-V1 pathway forms a differential circuit with the canonical retino-geniculate pathway to achieve context-dependent sharpening of visual representations.

Perineuronal nets (PNs) are a unique and complex meshwork of specific extracellular matrix molecules that ensheath a subset of neurons in many regions of the central nervous system (CNS). PNs appear late in development and are supposed to restrict synaptic plasticity and to stabilize functional neuronal connections. PNs were further hypothesized to create a charged milieu around the neurons and thus, might directly modulate synaptic activity. Although PNs were first described more than 120 years ago, their exact functions still remain elusive. The purpose of the present review is to propose the nuclei of the auditory system, which are highly enriched in PN-wearing neurons, as particularly suitable structures to study the functional significance of PNs. We provide a detailed description of the distribution of PNs from the cochlear nucleus to the auditory cortex considering distinct markers for detection of PNs. We further point to the suitability of specific auditory neurons to serve as promising model systems to study in detail the contribution of PNs to synaptic physiology and also more generally to the functionality of the brain.

Dysfunctional sensory gating has been proposed to result in the generation of phantom perceptions. In agreement, it has been recently suggested that tinnitus, a phantom perception of sound commonly associated with hearing loss, is the result of a breakdown of circuitry involving the limbic system and the medial geniculate nucleus (MGN) of the thalamus. In humans with tinnitus, structural changes and abnormal activity have been found to occur in the auditory pathway as well as parts of the limbic system such as the nucleus accumbens (NAc). However, at present, no studies have been conducted on the influence of the NAc on the MGN. We investigated the functional connectivity between the NAc and MGN single neurons. Bipolar electrical stimulation was delivered to the NAc while recording single neuron activity in MGN in anesthetized Wistar rats. Histological analysis was used to confirm placement of electrodes. NAc electrical stimulation generally decreased spontaneous firing rates in MGN neurons and, in a limited number of neurons, caused an increase in firing rate. This suggests that NAc can modulate the activity of auditory neurons in the MGN and may play a role in the development of tinnitus.

SummaryThe spatial arrangement of luminance increments (ON) and decrements (OFF) falling on the retina provides a wealth of information used by central visual pathways to construct coherent representations of visual scenes. But how the polarity of luminance change is represented in the activity of cortical circuits remains unclear. Using wide-field epifluorescence and two-photon imaging we demonstrate a robust modular representation of luminance polarity (ON or OFF) in the superficial layers of ferret primary visual cortex. Polarity-specific domains are found with both uniform changes in luminance and single light/dark edges, and include neurons selective for orientation and direction of motion. The integration of orientation and polarity preference is evident in the selectivity and discrimination capabilities of most layer 2/3 neurons. We conclude that polarity selectivity is an integral feature of layer 2/3 neurons, ensuring that the distinction between light and dark stimuli is available for further processing in downstream extrastriate areas.

Deprivation of patterned vision of frontal eyed mammals early in postnatal life alters structural and functional attributes of neurones in the central visual pathways, and can produce severe impairments of the vision of the deprived eye that resemble the visual loss observed in human amblyopia. A traditional approach to treatment of amblyopia has been the occlusion of the stronger fellow eye in order to force use of the weaker eye and thereby strengthen its connections in the visual cortex. Although this monocular treatment strategy can be effective at promoting recovery of visual acuity of the amblyopic eye, such binocular visual functions as stereoscopic vision often remain impaired due in part to the lack of concordant vision during the period of unilateral occlusion. The recent development of binocular approaches for treatment of amblyopia that improve the possibility for binocular interaction have achieved success in promoting visual recovery. The full and rapid recovery of visual acuity observed in amblyopic kittens placed in complete darkness is an example of a binocular treatment whose success may in part derive from a restored balance of visually-driven neural activity. In the current study we examined as an alternative to dark rearing the efficacy of binocular lid suture (BLS) to stimulate anatomical and visual recovery from a preceding amblyogenic period of monocular deprivation. In the dorsal lateral geniculate nucleus (dLGN) of monocularly deprived kittens, darkness or BLS for 10days produced a complete recovery of neurone soma size within initially deprived layers. The growth of neurone somata within initially deprived dLGN layers after darkness or BLS was accompanied by an increase in neurotrophin-4/5 labeling within these layers. Although anatomical recovery was observed in both recovery conditions, BLS failed to promote any improvement of the visual acuity of the deprived eye no matter whether it followed immediately or was delayed with respect to the prior period of monocular deprivation. Notwithstanding the lack of visual recovery with BLS, all animals in the BLS condition that were subsequently placed in darkness exhibited a substantial recovery of visual acuity in the amblyopic eye. We conclude that the balanced binocular visual input provided by BLS does not stimulate the collection of neural events necessary to support recovery from amblyopia. The complete absence of visually-driven activity that occurs with dark rearing evidently plays an important role in the recovery process.

Although the neural locus of strabismic amblyopia has been shown to lie at the first site of binocular integration, first in cat and then in primate, an adequate mechanism is still lacking. Here we hypothesise that increased temporal dispersion of LGN X-cell afferents driven by the deviating eye onto single cortical neurons may provide a neural mechanism for strabismic amblyopia. This idea was investigated via single cell extracellular recordings of 93 X and 50 Y type LGN neurons from strabismic and normal cats. Both X and Y neurons driven by the non-deviating eye showed shorter latencies than those driven by either the strabismic or normal eyes. Also the mean latency difference between X and Y neurons was much greater for the strabismic cells compared with the other two groups. The incidence of lagged X-cells driven by the deviating eye of the strabismic cats was higher than that of LGN X-cells from normal animals. Remarkably, none of the cells recorded from the laminae driven by the non-deviating eye were of the lagged class. A simple computational model was constructed in which a mixture of lagged and non-lagged afferents converge on to single cortical neurons. Model cut-off spatial frequencies to a moving grating stimulus were sensitive to the temporal dispersion of the geniculate afferents. Thus strabismic amblyopia could be viewed as a lack of developmental tuning of geniculate lags for neurons driven by the amblyopic eye. Monocular control of fixation by the non-deviating eye is associated with reduced incidence of lagged neurons, suggesting that in normal vision, lagged neurons might play a role in maintaining binocular connections for cortical neurons.

A common feature of the mammalian striate cortex is the arrangement of 'orientation domains' containing neurons preferring similar stimulus orientations. They are arranged as spokes of a pinwheel that converge at singularities known as 'pinwheel centers'. We propose that a cortical network of feedforward and intracortical lateral connections elaborates a full set of optimum orientations from geniculate inputs that show a bias to stimulus orientation and form a set of two or a small number of 'Cartesian' coordinates. Because each geniculate afferent carries signals only from one eye and its receptive field (RF) is either ON or OFF center, the network constructs also ocular dominance columns and a quasi-segregation of ON and OFF responses across the horizontal extent of the striate cortex.

Auditory thalamus (medial geniculate body [MGB]) receives ascending inhibitory GABAergic inputs from inferior colliculus (IC) and descending GABAergic projections from the thalamic reticular nucleus (TRN) with both inputs postulated to play a role in shaping temporal responses. Previous studies suggested that enhanced processing of temporally rich stimuli occurs at the level of MGB, with our recent study demonstrating enhanced GABA sensitivity in MGB compared to IC. The present study used sinusoidal amplitude-modulated (SAM) stimuli to generate modulation transfer functions (MTFs), to examine the role of GABAergic inhibition in shaping the response properties of MGB single units in anesthetized rats. Rate MTFs (rMTFs) were parsed into "bandpass (BP)", "mixed (Mixed)", "highpass (HP)" or "atypical" response types, with most units showing the Mixed response type. GABAA receptor blockade with iontophoretic application of the GABAA receptor (GABAAR) antagonist gabazine (GBZ) selectively altered the response properties of most MGB neurons examined. Mixed and HP units showed significant GABAAR-mediated SAM-evoked rate response changes at higher modulation frequencies (fms), which were also altered by N-methyl-d-aspartic acid (NMDA) receptor blockade (2R)-amino-5-phosphonopentanoate (AP5). BP units, and the lower arm of Mixed units responded to GABAAR blockade with increased responses to SAM stimuli at or near the rate best modulation frequency (rBMF). The ability of GABA circuits to shape responses at higher modulation frequencies is an emergent property of MGB units, not observed at lower levels of the auditory pathway and may reflect activation of MGB NMDA receptors (Rabang and Bartlett, 2011; Rabang et al., 2012). Together, GABAARs exert selective rate control over selected fms, generally without changing the units' response type. These results showed that coding of modulated stimuli at the level of auditory thalamus is at least, in part, strongly controlled by GABA neurotransmission, in delicate balance with glutamatergic neurotransmission.

"Metaplasticity" is defined as an alteration of synaptic plasticity properties or mechanisms by a priming event without actual changes in synaptic strength. For example, visual discrimination training of rats leads to a facilitation of the subsequent induction of long-term potentiation (LTP) between the lateral geniculate nucleus (LGN) and the primary visual cortex (V1). Here, rats received visual discrimination training in a modified water maze, with one eye occluded during training to create monocular viewing conditions; 63% of rats acquired the task under these conditions. Following training, in vivo electrophysiology was used to examine LTP of field postsynaptic potentials (fPSPs) in V1 elicited by LGN stimulation. Rats that had successfully learned the task showed significantly greater LTP in the "trained V1" (contralateral to the open, trained eye) relative to the "untrained" hemisphere. Rats that underwent training but failed to acquire the task did not show this lateralized plasticity enhancement and had similar levels of LTP in both cerebral hemispheres. Cortical application of the NMDA receptor-GluN2B subunit antagonist Ro 25-6981 (2 mM) reversed the training-induced LTP facilitation without affecting LTP in the untrained V1. Whole-cell patch clamp recordings of V1 (layers II/III) pyramidal cells in vitro demonstrated that pharmacologically isolated NMDA currents exhibit a greater sensitivity to GluN2B blockade in the trained relative to the untrained V1. Together, these experiments reveal a surprising degree of anatomical (only in the hemisphere contralateral to the trained eye) and behavioral specificity (only in rats that mastered the task) for the effect of visual training to enhance LTP in V1. Further, cortical GluN2B subunits appear to be directly involved in this metaplastic facilitation of thalamocortical plasticity, suggesting that NMDA subunit composition or functioning is, at least in part, regulated by the exposure to behaviorally significant stimuli in an animal's sensory environment.

Malformations of cortical development (MCD) have been observed in human reading and language impaired populations. Injury-induced MCD in rodent models of reading disability show morphological changes in the auditory thalamic nucleus (medial geniculate nucleus; MGN) and auditory processing impairments, thus suggesting a link between MCD, MGN, and auditory processing behavior. Previous neuroanatomical examination of a BXD29 recombinant inbred strain (BXD29- Tlr4 lps−2J /J) revealed MCD consisting of bilateral subcortical nodular heterotopia with partial callosal agenesis. Subsequent behavioral characterization showed a severe impairment in auditory processing—a deficient behavioral phenotype seen across both male and female BXD29- Tlr4 lps−2J /J mice. In the present study we expanded upon the neuroanatomical findings in the BXD29- Tlr4 lps−2J /J mutant mouse by investigating whether subcortical changes in cellular morphology are present in neural structures critical to central auditory processing (MGN, and the ventral and dorsal subdivisions of the cochlear nucleus; VCN and DCN, respectively). Stereological assessment of brain tissue of male and female BXD29- Tlr4 lps−2J /J mice previously tested on an auditory processing battery revealed overall smaller neurons in the MGN of BXD29- Tlr4 lps−2J /J mutant mice in comparison to BXD29/Ty coisogenic controls, regardless of sex. Interestingly, examination of the VCN and DCN revealed sexually dimorphic changes in neuronal size, with a distribution shift toward larger neurons in female BXD29- Tlr4 lps−2J /J brains. These effects were not seen in males. Together, the combined data set supports and further expands the observed co-occurrence of MCD, auditory processing impairments, and changes in subcortical anatomy of the central auditory pathway. The current stereological findings also highlight sex differences in neuroanatomical presentation in the presence of a common auditory behavioral phenotype.

Prompt detection of unexpected changes in the sensory environment is critical for survival. In the auditory domain, the occurrence of a rare stimulus triggers a cascade of neurophysiological events spanning over multiple time-scales. Besides the role of the mismatch negativity (MMN), whose cortical generators are located in supratemporal areas, cumulative evidence suggests that violations of auditory regularities can be detected earlier and lower in the auditory hierarchy. Recent human scalp recordings have shown signatures of auditory mismatch responses at shorter latencies than those of the MMN. Moreover, animal single-unit recordings have demonstrated that rare stimulus changes cause a release from stimulus-specific adaptation in neurons of the primary auditory cortex, the medial geniculate body (MGB), and the inferior colliculus (IC). Although these data suggest that change detection is a pervasive property of the auditory system which may reside upstream cortical sites, direct evidence for the involvement of subcortical stages in the human auditory novelty system is lacking. Using event-related functional magnetic resonance imaging during a frequency oddball paradigm, we here report that auditory deviance detection occurs in the MGB and the IC of healthy human participants. By implementing a random condition controlling for neural refractoriness effects, we show that auditory change detection in these subcortical stations involves the encoding of statistical regularities from the acoustic input. These results provide the first direct evidence of the existence of multiple mismatch detectors nested at different levels along the human ascending auditory pathway. This work was supported by the Spanish Ministry of Economy and Knowledge (PSI2012-37174) and the program Consolider-Ingenio 2010 (CSD2007-00012), the Catalan Government (SGR2014-177), and the ICREA Academia Distinguished Professorship awarded to Carles Escera.