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Introduction: Transient phenomena play a key role in coordinating brain activity at multiple scales, however their underlying mechanisms remain largely unknown. A key challenge for neural data science is thus to characterize the network interactions at play during these events.Methods: Using the formalism of Structural Causal Models and their graphical representation, we investigate the theoretical and empirical properties of Information Theory based causal strength measures in the context of recurring spontaneous transient events.Results: After showing the limitations of Transfer Entropy and Dynamic Causal Strength in this setting, we introduce a novel measure, relative Dynamic Causal Strength, and provide theoretical and empirical support for its benefits.Discussion: These methods are applied to simulated and experimentally recorded neural time series and provide results in agreement with our current understanding of the underlying brain circuits.

Illusions are a powerful tool for studying the single neuron correlates of perception. Here, we introduce the neon color spreading (NCS) illusion in mice and report the neuronal correlates of illusory brightness, which has heretofore only been studied using human fMRI. We designed a novel NCS paradigm to evoke the percept of an illusory drifting grating and analyzed the activity of 520 single units in the mouse primary visual cortex (V1). A substantial proportion of V1 single units (60.5%) responded to illusory gratings with direction tuning matched to their preferred direction, which was determined using physically presented luminance-defined gratings (LDG). Moreover, by presenting LDG gratings with a 180° phase shift relative to NCs gratings, we show that spatial phase tuning shifted 180° for most single units. This finding conclusively demonstrates that V1 single units respond to illusory brightness. Using this novel mouse paradigm, we show that responses to illusory gratings have a lower magnitude and are delayed relative to physical gratings. We determined where V1 single units fell in the V1 cellular hierarchy (based on their susceptibility to surround suppression, their putative classification as interneuron or pyramidal neuron, and designation as a simple or complex cell) and found that higher-level V1 single units are more responsive to NCS stimuli. These findings resolve the debate of whether V1 is involved in illusory brightness processing and reveal a V1 hierarchical organization in which higher-level neurons are pivotal to the processing of illusory qualities, such as brightness.

Despite the considerable progress ofin vivoneural recording techniques, inferring the biophysical mechanisms underlying large scale coordination of brain activity from neural data remains challenging. One obstacle is the difficulty to link high dimensional functional connectivity measures to mechanistic models of network activity. We address this issue by investigating spike-field coupling (SFC) measurements, which quantify the synchronization between, on the one hand, the action potentials produced by neurons, and on the other hand a mesoscopic “field” signals, reflecting subthreshold activities at possibly multiple recording sites. As the number of recording sites gets large, the amount of pairwise SFC measurements becomes overwhelmingly challenging to interpret. We developGeneralized Phase Locking Analysis(GPLA) as a dimensionality reduction of this multivariate SFC. GPLA describes the dominant coupling between field activity and neural ensembles across space and frequencies, thereby providing rich yet interpretable information. In particular, we show that GPLA features arebiophysically interpretablewhen used in conjunction with appropriate network models, such that we can identify the influence of underlying circuit properties on these features. We demonstrate the statistical benefits and interpretability of this approach in various computational models and Utah array recordings. The results suggest that GPLA used jointly with biophysical modeling can help uncover the contribution of recurrent microcircuits to the spatio-temporal dynamics observed in multi-channel experimental recordings.

Cortical slow rhythmic activity, a hallmark of deep sleep, is observed under urethane anesthesia. Synchronized fluctuations of the membrane excitability of a large neuronal population are reflected in the extracellular Local Field Potential (LFP), as high-amplitude slow (∼1 Hz) oscillations (SO). The SO-phase indicates the presence (Up) or absence (Down) of neuronal spiking. The cortical state is controlled by the input from thalamic and neuromodulatory centers, including the brainstem noradrenergic nucleus Locus Coeruleus (LC). The bidirectional modulation of neuronal excitability by noradrenaline (NA) is well known. We have previously shown that LC phasic activation caused transient excitability increase in the medial prefrontal cortex (mPFC). In the present study, we characterized the effect of LC phasic activation on the prefrontal population dynamics at a temporal scale of a single SO cycle. We applied short (0.2 s) trains of electric pulses (0.02–0.05 mA at 20–50 Hz) to the LC cell bodies and monitored a broadband (0.1 Hz–8 kHz) mPFC LFP in urethane-anesthetized rats. The direct electrical stimulation of LC (LC-DES), applied during the Up-phase, enhanced the firing probability in the mPFC by ∼20% and substantially prolonged Up-states in 56% of trials. The LC-DES applied during Down-phase caused a rapid Down-to-Up transition in 81.5% of trials. The LC-DES was more effective at a higher frequency, but not at a higher current. Our results suggest that transient NA release, coupled to SO, may promote synaptic plasticity and memory consolidation by sustaining a depolarized state in the mPFC neurons.

An alerting sound elicits the Acoustic Startle Response (ASR) that is dependent on the sound volume and organisms’ state, which is regulated by neuromodulatory centers. The locus coeruleus (LC) neurons respond to salient stimuli and noradrenaline release affects sensory processing, including auditory. The LC hyperactivity is detrimental for sensorimotor gating. We report here that priming microstimulation of the LC (100-ms at 20, 50, and 100 Hz) attenuated the ASR in rats. The ASR reduction scaled with frequency and 100 Hz-stimulation mimicked pre-exposure to a non-startling tone (prepulse). A rapid (~ 40 ms) EEG desynchronization following the LC stimulation suggested that the ASR reduction was due to elevated cortical arousal. The effects of LC stimulation on the ASR and EEG were consistent with systematic relationships between the ASR, awake/sleep state, and the cortical arousal level; for that matter, a lower ASR amplitude corresponded to a higher arousal level. Thus, the LC appears to modulate the ASR circuit via its diffuse ascending projections to the forebrain saliency network. The LC modulation directly in the brainstem and/or spinal cord may also play a role. Our findings suggest the LC as a part of the brain circuitry regulating the ASR, while underlying neurophysiological mechanisms require further investigation.

The noradrenergic locus coeruleus (LC) is a controller of brain and behavioral states. Activating LC neurons en masse by electrical or optogenetic stimulation promotes a stereotypical "activated" cortical state of high-frequency oscillations. However, it has been recently reported that spontaneous activity of LC cell pairs has sparse yet structured time-averaged cross-correlations, which is unlike the highly synchronous neuronal activity evoked by stimulation. Therefore, LC population activity could consist of distinct multicell ensembles each with unique temporal evolution of activity. We used nonnegative matrix factorization (NMF) to analyze large populations of simultaneously recorded LC single units in the rat LC. NMF identified ensembles of spontaneously coactive LC neurons and their activation time courses. Since LC neurons selectively project to specific forebrain regions, we hypothesized that distinct ensembles activate during different cortical states. To test this hypothesis, we calculated band-limited power and spectrograms of local field potentials in cortical area 24a aligned to spontaneous activations of distinct LC ensembles. A diversity of state modulations occurred around activation of different LC ensembles, including a typical activated state with increased highfrequency power as well as other states including decreased high-frequency power. Thus-in contrast to the stereotypical activated brain state evoked by en masse LC stimulation-spontaneous activation of distinct LC ensembles is associated with a multitude of cortical states.

The hippocampus has a major role in encoding and consolidating long-term memories, and undergoes plastic changes during sleep1. These changes require precise homeostatic control by subcortical neuromodulatory structures2. The underlying mechanisms of this phenomenon, however, remain unknown. Here, using multi-structure recordings in macaque monkeys, we show that the brainstem transiently modulates hippocampal network events through phasic pontine waves known as pontogeniculooccipital waves (PGO waves). Two physiologically distinct types of PGO wave appear to occur sequentially, selectively influencing high-frequency ripples and low-frequency theta events, respectively. The two types of PGO wave are associated with opposite hippocampal spike-field coupling, prompting periods of high neural synchrony of neural populations during periods of ripple and theta instances. The coupling between PGO waves and ripples, classically associated with distinct sleep stages, supports the notion that a global coordination mechanism of hippocampal sleep dynamics by cholinergic pontine transients may promote systems and synaptic memory consolidation as well as synaptic homeostasis.

The human brain is a biological organ, weighing about three pounds or 1.4 kg, that determines our behaviors, thoughts, emotions and consciousness. Although comprising only 2% of the total body weight, the brain consumes about 20% of the oxygen entering the body. With the expensive energy demand, the brain enables us to perceive and act upon the external world, as well as reflect on our internal thoughts and feelings. The brain is actually never at ‘rest’. Brain activities continue around the clock, ranging from functions enabling human–environment interactions to housekeeping during sleep, including processes such as synaptic homeostasis and memory formation. Whereas one could argue that sciences in the last century were dominated by physics and molecular biology, in the current century one of our major challenges is to elucidate how the brain works. A full understanding of brain functions and malfunctions is likely the most demanding task we will ever have.

This study presents brain electrophysiological characteristics of perspective-taking for blind individuals ver. sighted ones, aiming to extend our knowledge on social concept formation with visual sensory modality loss. A blind and a sighted group instructed to consider the moral dilemmas therein from a neutral (observer), a morally positive or a negative stance, after the auditory presentation of Aesop’s fables. We recorded the basic emotions evoked by every stance in each fable, and the late positive potentials (LPP) component of Event-Related Potential detected with Continuous Wavelet Transform, believed to reflect the sustained attention and stimuli encoding processes. Blind participants demonstrated: i) significantly attenuated LPP amplitudes at distributed brain areas, particularly at leads T3, P4, O2, T6, Cz, Pz, CPz and CP4 (p values 0.026-0.003), ii) prolonged LPP latencies at parietal areas, at leads CP4 (p=0.009), Pz (p=0.019), and P4 (p=0.023), iii) shorter latencies at the frontal area (lead FPz, p=0.026) and iv) significantly shorter latencies at the right posterior centrotemporal area under the negative than the positive condition (lead C4, p=0.009). Both groups exhibited higher LPP amplitudes under the morally positive, and lower under the negative condition located at the parietal areas (P3, p=0.001 and CPz, p=0.013). The relationships between behavior and LPP activation conform to the proposed generation and modulation of LPP. Our findings suggest that the visually deprived cortex may become more responsive to processes associated with perspective-taking, possibly through compensatory plasticity enabling cross-modal reorganization. Thus, the study introduces a novel model for accessing the sustained attention and stimulus-encoding processes underlying perspective-taking.

Contemporary neuroscience and psychiatry suggest that attention to decision outcomes guides rule learning by adjusting stimulus-outcome associations. Separately, sensory neurophysiology conceptualizes attention as a ‘filter’ that improves perception. Here, we show that the contemporary view is incomplete by demonstrating an unconventional and novel effect of perceptual attention on subsequent outcome-based rule learning. Moreover, we show for the first time in rodents that, like in primates, this attentional process involves tuning of modality specific cortico-cortical interactions. We designed a novel head-fixed rat-on-a-treadmill apparatus and used it to train rats to discriminate auditory-visual stimuli using one modality and then reduced stimulus discriminability in that modality. We observed perceptual learning suggesting engagement of perceptual attention. Moreover, engaging visual perceptual attention resulted in more saccades and increased frontal-visual cortex EEG Granger causality relative to engaging auditory perceptual attention. We then presented novel and easily discriminable stimuli in both modalities and measured outcome-driven learning in the other modality. Learning was slower after engaging perceptual attention. Our work suggests that a more complete description of learning requires integrating these previously siloed concepts of attention. Moreover, treating impaired set-shifting as a trans-diagnostic symptom may require targeting different neural circuits for perceptual attention or outcome-based attention depending on which type of attention is impaired in each neuro-psychiatric disorder.

Water restriction is commonly used to motivate rodents to perform behavioral tasks; however, its on hydration and stress hormone levels are unknown. Here, we report daily body weight and bi-weekly packed red blood cell volume and corticosterone in adult male rats across 80 days for three commonly used water restriction schedules. We also assessed renal adaptation to water restriction using post-mortem histological evaluation of renal medulla. A control group received ad libitum water. After one week of water restriction, rats on all restriction schedules resumed similar levels of growth relative to the control group. Nominal hydration was observed, and water restriction did not drive renal adaptation. An intermittent restriction schedule was associated with an increase in corticosterone relative to the control group. Our results suggest that the water restriction schedules used here will maintain welfare in rats. However, intermittent restriction evokes a stress response which could affect behavioral and neurobiological results. Our results also suggest that stable motivation in behavioral tasks may only be achieved after one week of restriction.

Water restriction is commonly used to motivate rodents to perform behavioral tasks; however, its effects on hydration and stress hormone levels are unknown. Here, we report daily body weight and bi-weekly packed red blood cell volume and corticosterone (CORT) in adult male rats across 80 days for three commonly used water restriction schedules. We also assessed renal adaptation to water restriction using postmortem histologic evaluation of renal medulla. A control group received ad libitum water. After one week of water restriction, rats on all restriction schedules resumed similar levels of growth relative to the control group. Normal hydration was observed, and water restriction did not drive renal adaptation. An intermittent restriction schedule was associated with an increase in CORT relative to the control group. However, intermittent restriction evokes a stress response which could affect behavioral and neurobiological results. Our results also suggest that stable motivation in behavioral tasks may only be achieved after one week of restriction.

Digitized neuroanatomical atlases that can be overlaid onto functional data are crucial for localizing brain structures and analyzing functional networks identified by neuroimaging techniques. To aid in functional and structural data analysis, we have created a comprehensive parcellation of the rhesus macaque subcortex using a high-resolution ex vivo structural imaging scan. This anatomical scan and its parcellation were warped to the updated NIMH Macaque Template (NMT v2), an in vivo population template, where the parcellation was refined to produce the Subcortical Atlas of the Rhesus Macaque (SARM) with 210 primary regions-of-interest (ROIs). The subcortical parcellation and nomenclature reflect those of the 4th edition of the Rhesus Monkey Brain in Stereotaxic Coordinates ( Paxinos et al., in preparation ), rather than proposing yet another novel atlas. The primary ROIs are organized across six spatial hierarchical scales from small, fine-grained ROIs to broader composites of multiple ROIs, making the SARM suitable for analysis at different resolutions and allowing broader labeling of functional signals when more accurate localization is not possible. As an example application of this atlas, we have included a functional localizer for the dorsal lateral geniculate (DLG) nucleus in three macaques using a visual flickering checkerboard stimulus, identifying and quantifying significant fMRI activation in this atlas region. The SARM has been made openly available to the neuroimaging community and can easily be used with common MRI data processing software, such as AFNI, where the atlas has been embedded into the software alongside cortical macaque atlases.

Significance The duration of cerebral ischemia is a key factor in determining the severity of brain damage and the course of action. Thus, an accurate and timely observation of the ischemic process is highly critical. Here we present a molecular neuroimaging approach that enables direct detection and real-time visualization of transient cerebral ischemia. The method relies on high-resolution observation of extracellular calcium alterations associated with the spatiotemporal dynamics of cerebral ischemia, using a selective molecular MRI probe. The rapid detection of calcium fluctuations in healthy and disease states will not only lead to essential insights for successful treatment and recovery of ischemic brain tissue but will also improve our understanding of the underlying neurobiology of neurological and psychiatric disorders., Cerebral ischemia is one of the leading causes of mortality and disability in infants and adults and its timely diagnosis is essential for an efficient treatment. We present a methodology for fast detection and real-time monitoring of fluctuations of calcium ions associated with focal ischemia using a molecular functional MRI approach. We used a dinuclear paramagnetic gadolinium(III) complex chelate that changes MR image contrast through its reversible interaction with extracellular calcium ions, while applying a remote transient middle cerebral artery occlusion as a model for ischemic stroke. Our method sensitively recognizes the onset and follows the dynamics of the ischemic core and penumbra with submillimeter spatial and second-scale temporal resolution, thus paving the way for noninvasive monitoring and development of targeted treatment strategies for cerebral ischemia.

Significance Neuroimaging studies suggest differences in the underlying biology of sexual arousal associated with sex and sexual orientation, yet their findings are conflicting. Following a thorough statistical review of all significant neuroimaging studies, we offer strong quantitative evidence that the neuronal response to visual sexual stimuli, contrary to the widely accepted view, is independent of biological sex. Both men and women show increased activation in many cortical and subcortical brain regions thought to be involved in the response to visual sexual stimuli, while the limited sex differences that have been found and reported previously refer to subjective rating of the content., Sexual arousal is a dynamical, highly coordinated neurophysiological process that is often induced by visual stimuli. Numerous studies have proposed that the cognitive processing stage of responding to sexual stimuli is the first stage, in which sex differences occur, and the divergence between men and women has been attributed to differences in the concerted activity of neural networks. The present comprehensive metaanalysis challenges this hypothesis and provides robust quantitative evidence that the neuronal circuitries activated by visual sexual stimuli are independent of biological sex. Sixty-one functional magnetic resonance imaging studies (1,850 individuals) that presented erotic visual stimuli to men and women of different sexual orientation were identified. Coordinate-based activation likelihood estimation was used to conduct metaanalyses. Sensitivity and clustering analyses of averaged neuronal response patterns were performed to investigate robustness of the findings. In contrast to neutral stimuli, sexual pictures and videos induce significant activations in brain regions, including insula, middle occipital, anterior cingulate and fusiform gyrus, amygdala, striatum, pulvinar, and substantia nigra. Cluster analysis suggests stimulus type as the most, and biological sex as the least, predictor for classification. Contrast analysis further shows no significant sex-specific differences within groups. Systematic review of sex differences in gray matter volume of brain regions associated with sexual arousal (3,723 adults) did not show any causal relationship between structural features and functional response to visual sexual stimuli. The neural basis of sexual arousal in humans is associated with sexual orientation yet, contrary to the widely accepted view, is not different between women and men.

International audience; Thanks to their versatile magnetic and luminescence features, lanthanide complexes have gained a central position in biomedical imaging as magnetic resonance imaging (MRI) contrast agents and optical imaging probes. In addition, appropriate chemical design allows modification of the magnetic relaxation properties of GdIII complexes and the optical properties of visible- or near-infrared (NIR)-emitting lanthanide chelates upon interaction with various biomarkers, which makes them ideal candidates for the creation of responsive agents. In this Forum Article, we demonstrate such design principles as well as the difficulties encountered in the context of neurotransmitter (NT) detection. Lanthanide(III) complexes of a macrocyclic ligand incorporating a benzophenone chromophore and a monoazacrown ether (LnL3) have been synthesized as responsive probes to monitor amino acid NTs either in MRI (Ln = Gd) or in NIR optical detection (Ln = Nd or Yb). The parameters characterizing the water exchange and rotational dynamics of the gadolinium(III) complex were assessed by 17O NMR and 1H NMRD. In the presence of zwitterionic NTs, the inner-sphere water molecule is replaced by the carboxylate function of the NTs in the gadolinium(III) complex, leading to a decrease of the longitudinal relaxivity from 6.7 to 2–2.5 mM–1 s–1 (300 MHz and 37 °C). The apparent affinity constants range from Ka = 35 for γ-aminobutyric acid (GABA) to 80 M–1 for glycine and glutamate, and there is no selectivity with respect to hydrogen carbonate (Ka = 232; pH 7.4). The gadolinium(III) complex interacts with human serum albumin (HSA), resulting in a 60% increase in the relaxivity (20 MHz, 37 °C) in the absence of NTs. The HSA-bound complex, however, was revealed to be less responsive to NTs because of displacement of the GdIII-bound water by HSA, which was confirmed by the hydration number calculated from luminescence lifetimes of the HSA-bound europium(III) complex. The creation of an imaging agent suitable for NIR detection of NTs for an enhanced sensitivity in biological systems using the benzophenone (BP) moiety as the sensitizer of lanthanide luminescence was also attempted. Upon excitation at 300 nm of the BP chromophore in aqueous solutions of NdL3 and YbL3, characteristic NIR emissions of NdIII and YbIII were observed because of 4F3/2 → 4IJ (J = 9/2–13/2) and 2F5/2 → 2F7/2 transitions, respectively, indicating that this chromophore is a suitable antenna. Despite these promising results, luminescence titrations of NdIII and YbIII complexes with NTs were not conclusive because of chemical conversion of the ligand triggered by light, preventing quantitative analysis. The observed photochemical reaction of the ligand is strongly dependent on the nature of the lanthanide chelated; it is considerably slowed down in the presence of NdIII and EuIII.

The brainstem noradrenergic locus coeruleus (LC) is reciprocally connected with the prefrontal cortex (PFC). Coupling between LC spiking and the depolarizing phase of slow (1?2 Hz) waves in PFC field potentials during sleep and anesthesia suggests that LC drives cortical state transition. Reciprocal LC-PFC connectivity should also allow interactions in the opposing (top-down) direction, but prior work has only studied prefrontal control over LC activity using electrical or optogenetic stimulation. Here, we describe the physiological characteristics of spontaneously occurring top-down LC-PFC interactions. We recorded LC multiunit activity (MUA) simultaneously with PFC single-unit and local field potential (LFP) activity in urethane-anesthetized rats. We observed cross-regional coupling between the phase of 5-Hz oscillations in LC-MUA and the power of PFC LFP 60?200 Hz high y (hy). Transient increases in PFC hy power preceded peaks in the 5-Hz LC-MUA oscillation. Analysis of cross-regional transfer entropy demonstrated that the PFC hy transients were predictive of a transient increase in LC-MUA. An -29 ms delay between these signals was consistent with the conduction velocity from the PFC to the LC. Finally, we showed that PFC hy transients are associated with synchronized spiking of a subset (27%) of PFC single units. Our data suggest that PFC hy transients may indicate the timing of the top-down excitatory input to LC, at least under conditions when LC neuronal population activity fluctuates rhythmically at 5 Hz. Synchronized PFC neuronal spiking that occurs during hy transients may provide a previously unknown mode of top-down control over the LC. NEW & NOTEWORTHY The prefrontal cortex (PFC) is thought to control activity in the noradrenergic locus coeruleus (LC). Prior anatomical and prefrontal stimulation studies demonstrated the potential for PFC-LC interactions; however, it is unknown what types of PFC activity affect the LC. Here, we show that transient increases in PFC high y power and associated changes in PFC unit-pair synchrony are a potential sign of top-down control over the LC.

During sleep, cortical network connectivity likely undergoes both synaptic potentiation and depression through system consolidation and homeostatic processes. However, how these modifications are coordinated across sleep stages remains largely unknown. Candidate mechanisms are Ponto-Geniculo-Occipital (PGO) waves, propagating across several structures during Rapid Eye Movement (REM) sleep and the transitional stage from non-REM sleep to REM sleep (pre-REM), and exhibiting sleep stage-specific dynamic patterns. To understand their impact on cortical plasticity, we built an acetylcholine-modulated neural mass model of PGO wave propagation through pons, thalamus and cortex, reproducing a broad range of electrophysiological characteristics across sleep stages. Using a population model of Spike-Time-Dependent Plasticity, we show that cortical circuits undergo different transient regimes depending on the sleep stage, with different impacts on plasticity. Specifically, PGO-induced recurrent cortical activities lead to the potentiation of cortico-cortical synapses during pre-REM, and to their depression during REM sleep. Overall, these results shed light on how the dynamical properties of sleep events propagating to cortical circuits can favor different types of local plastic changes. The variety of events occurring across sleep stages may thus be instrumental in controlling the reorganization of cortical networks from one day to the next.Significance statementConsiderable evidence supports rescaling of cortical synaptic connec-tions during sleep, requiring both long term potentiation to consolidate newly acquired memories, and long-term depression to maintain homeostatic levels of brain activity. However, which aspects of sleep activity contribute to this bidirectional control of plasticity remains unclear. This computational modeling study suggests that widespread transient phenomena called Ponto-geniculo-occipital (PGO) waves, have a sleep-stage dependent effect on plasticity. The alternation between sleep stages can thus be exploited in combination with spontaneously occurring transients, to trigger both up- and down-regulating effects on cortical connectivity, and may explain why the basic structure of sleep-cycles is a well-preserved property across mammalian species.

The insula has been classically divided into vast granular, dysgranular and agranular sectors. Over the years, several distinct studies proposed subdivisions of these sectors, with however no consensus. We recently proposed a cyto- and myelo-architectonic partition in which each sector contained sharply delimited areas (Evrard et al. 2014 J Comp Neurol 522: 64-97). Some of these areas were further divided into distinct subareas with obvious functional implications. Here, we examined the spatial relationship between architectonic boundaries and tract-tracing labeling in the insula in the macaque monkey. Injections of neuronal tracers in distinct areas of the prefrontal or anterior cingulate cortices produced heterogeneous and discontinuous patterns of anterograde and retrograde labeling in the insula. These patterns were made of sharply delimited patches forming anteroposterior stripes across consecutive coronal sections. While the overall pattern of labeling varied with the injection site, the patches systematically coincided with specific architectonic subareas, particularly in the dysgranular insula. This unequivocally validates our prior architectonic partition and strongly supports the idea of a refined modular Bauplan of the primate insula. This modular organization may underlie a serial stream of integration of interoception with ‘self-agency’ and ‘social’ activities across distinct insulo-prefrontal processing units that need to be explored.

Summary Rats have been used as animal models for human diseases for more than a century, yet a systematic understanding of basal biobehavioral phenotypes of laboratory rats is still missing. In this study, we utilize wireless tracking technology and videography, collect and analyze more than 130 billion data points to fill this gap, and characterize the evolution of behavior and physiology of group-housed male and female rats (n = 114) of the most commonly used strains (Lister Hooded, Long-Evans, Sprague-Dawley, and Wistar) throughout their development. The resulting intensive longitudinal data suggest the existence of strain and sex differences and bi-stable developmental states. Under standard laboratory 12-h light/12-h dark conditions, our study found the presence of multiple oscillations such as circatidal-like rhythms in locomotor activity. The overall findings further suggest that frequent movement along cage walls or thigmotaxic activity may be a physical feature of motion in constrained spaces, critically affecting the interpretation of basal behavior of rats in cages.

Digitized neuroanatomical atlases are crucial for localizing brain structures and analyzing functional networks identified by magnetic resonance imaging (MRI). To aid in MRI data analysis, we have created a comprehensive parcellation of the rhesus macaque subcortex using a high-resolution ex vivo structural imaging scan. The structural scan and its parcellation were warped to the updated NIMH Macaque Template (NMT v2), an in vivo population template, where the parcellation was refined to produce the Subcortical Atlas of the Rhesus Macaque (SARM). The subcortical parcellation and nomenclature reflect those of the 4th edition of the Rhesus Monkey Brain in Stereotaxic Coordinates (RMBSC4; Paxinos et al., in preparation). The SARM features six parcellation levels, arranged hierarchically from fine regions-of-interest (ROIs) to broader composite regions, suited for fMRI studies. As a test, we ran a functional localizer for the dorsal lateral geniculate (DLG) nucleus in three macaques and found significant fMRI activation in this atlas region. The SARM has been made openly available to the neuroimaging community and can easily be used with common MR data processing software, such as AFNI, where the atlas can be embedded into the software alongside cortical macaque atlases.HighlightsWe present the Subcortical Atlas of the Rhesus Macaque (SARM).SARM provides a neuroanatomical reference frame for neuroimaging analysis.The entire subcortex is mapped, including the thalamus, basal ganglia, and brainstem.ROIs are grouped hierarchically, making SARM useful at multiple spatial resolutions.SARM is in the NMT v2 template space and complements the CHARM atlas for the cortex.