Mapping of the excitatory, inhibitory, and modulatory afferent projections to the anatomically defined active expiratory oscillator in adult male rats.

The lateral parafacial region (pFL ; which encompasses the parafacial respiratory group, pFRG) is a conditional oscillator that drives active expiration during periods of high respiratory demand, and increases ventilation through the recruitment of expiratory muscles. The pFL activity is highly modulated, and systematic analysis of its afferent projections is required to understand its connectivity and modulatory control. We combined a viral retrograde tracing approach to map direct brainstem projections to the putative location of pFL , with RNAScope and immunofluorescence to identify the neurochemical phenotype of the projecting neurons. Within the medulla, retrogradely-labeled, glutamatergic, glycinergic and GABAergic neurons were found in the ventral respiratory column (Bötzinger and preBötzinger Complex [preBötC], ventral respiratory group, ventral parafacial region [pFV ] and pFL ), nucleus of the solitary tract (NTS), reticular formation (RF), pontine and midbrain vestibular nuclei, and medullary raphe. In the pons and midbrain, retrogradely-labeled neurons of the same phenotypes were found in the Kölliker-Fuse and parabrachial nuclei, periaqueductal gray, pedunculopontine nucleus (PPT) and laterodorsal tegmentum (LDT). We also identified somatostatin-expressing neurons in the preBötC and PHOX2B immunopositive cells in the pFV , NTS, and part of the RF. Surprisingly, we found no catecholaminergic neurons in the NTS, A5 or Locus Coeruleus, no serotoninergic raphe neurons nor any cholinergic neurons in the PPT and LDT that projected to the pFL . Our results indicate that pFL neurons receive extensive excitatory and inhibitory inputs from several respiratory and nonrespiratory related brainstem regions that could contribute to the complex modulation of the conditional pFL oscillator for active expiration.

Afferent and efferent connections of the nucleus prethalamicus in the yellowfin goby Acanthogobius flavimanus.

The nucleus prethalamicus (PTh) receives fibers from the optic tectum and then projects to the dorsal telencephalon in the yellowfin goby Acanthogobius flavimanus. However, it remained unclear whether the PTh is a visual relay nucleus, because the optic tectum receives not only visual but also other sensory modalities. Furthermore, precise telencephalic regions receiving prethalamic input remained unknown in the goby. We therefore investigated the full set of afferent and efferent connections of the PTh by direct tracer injections into the nucleus. Injections into the PTh labeled cells in the optic tectum, ventromedial thalamic nucleus, central and medial parts of the dorsal telencephalon, and caudal lobe of the cerebellum. We found that the somata of most tecto-prethalamic neurons are present in the stratum periventriculare. Their dendrites ascend to reach the major retinorecipient layers of the tectum. The PTh is composed of two subnuclei (medial and lateral) and topographic organization was appreciated only for tectal projections to the lateral subnucleus (PTh-l), which also receives sparse retinal projections. In contrast, the medial subnucleus receives fibers only from the medial tectum. We found that the PTh projects to nine subregions in the dorsal telencephalon and four in the ventral telencephalon. Furthermore, cerebellar injections revealed that cerebello-prethalamic fibers cross the midline twice to innervate the PTh-l on both sides. The present study is the first detailed report on the full set of the connections of PTh, which suggests that the PTh relays visual information from the optic tectum to the telencephalon.

Central afferents to the nucleus of the solitary tract in rats and mice.

The nucleus of the solitary tract (NTS) regulates life-sustaining functions ranging from appetite and digestion to heart rate and breathing. It is also the brain's primary sensory nucleus for visceral sensations relevant to symptoms in medical and psychiatric disorders. To better understand which neurons may exert top-down control over the NTS, here we provide a brain-wide map of all neurons that project axons directly to the caudal, viscerosensory NTS, focusing on a medial subregion with aldosterone-sensitive HSD2 neurons. Injecting an axonal tracer (cholera toxin b) into the NTS produces a similar pattern of retrograde labeling in rats and mice. The paraventricular hypothalamic nucleus (PVH), lateral hypothalamic area, and central nucleus of the amygdala (CeA) contain the densest concentrations of NTS-projecting neurons. PVH afferents are glutamatergic (express Slc17a6/Vglut2) and are distinct from neuroendocrine PVH neurons. CeA afferents are GABAergic (express Slc32a1/Vgat) and are distributed largely in the medial CeA subdivision. Other retrogradely labeled neurons are located in a variety of brain regions, including the cerebral cortex (insular and infralimbic areas), bed nucleus of the stria terminalis, periaqueductal gray, Barrington's nucleus, Kölliker-Fuse nucleus, hindbrain reticular formation, and rostral NTS. Similar patterns of retrograde labeling result from tracer injections into different NTS subdivisions, with dual retrograde tracing revealing that many afferent neurons project axon collaterals to both the lateral and medial NTS subdivisions. This information provides a roadmap for studying descending axonal projections that may influence visceromotor systems and visceral "mind-body" symptoms.

Perineuronal nets and subtypes of GABAergic cells differentiate auditory and multisensory nuclei in the intercollicular area of the midbrain.

The intercollicular region, which lies between the inferior and superior colliculi in the midbrain, contains neurons that respond to auditory, visual, and somatosensory stimuli. Golgi studies have been used to parse this region into three distinct nuclei: the intercollicular tegmentum (ICt), the rostral pole of the inferior colliculus (ICrp), and the nucleus of the brachium of the IC (NBIC). Few reports have focused on these nuclei, especially the ICt and the ICrp, possibly due to lack of a marker that distinguishes these areas and is compatible with modern methods. Here, we found that staining for GABAergic cells and perineuronal nets differentiates these intercollicular nuclei in guinea pigs. Further, we found that the proportions of four subtypes of GABAergic cells differentiate intercollicular nuclei from each other and from adjacent inferior collicular subdivisions. Our results support earlier studies that suggest distinct morphology and functions for intercollicular nuclei, and provide staining methods that differentiate intercollicular nuclei and are compatible with most modern techniques. We hope that this will help future studies to further characterize the intercollicular region.

Central taste anatomy and physiology.

The gustatory system contributes to the flavor of foods and beverages and communicates information about nutrients and poisons. This system has evolved to detect and ultimately respond to hydrophilic molecules dissolved in saliva. Taste receptor cells, located in taste buds and distributed throughout the oral cavity, activate nerve afferents that project to the brainstem. From here, information propagates to thalamic, subcortical, and cortical areas, where it is integrated with information from other sensory systems and with homeostatic, visceral, and affective processes. There is considerable divergence, as well as convergence, of information between multiple regions of the central nervous system that interact with the taste pathways, with reciprocal connections occurring between the involved regions. These widespread interactions among multiple systems are crucial for the perception of food. For example, memory, hunger, satiety, and visceral changes can directly affect and can be affected by the experience of tasting. In this chapter, we review the literature on the central processing of taste with a specific focus on the anatomic and physiologic responses of single neurons. Emphasis is placed on how information is distributed along multiple systems with the goal of better understanding how the rich and complex sensations associated with flavor emerge from large-scale, systems-wide, interactions.

Monosynaptic tracing maps brain-wide afferent oligodendrocyte precursor cell connectivity.

Neurons form bona fide synapses with oligodendrocyte precursor cells (OPCs), but the circuit context of these neuron to OPC synapses remains incompletely understood. Using monosynaptically-restricted rabies virus tracing of OPC afferents, we identified extensive afferent synaptic inputs to OPCs residing in secondary motor cortex, corpus callosum, and primary somatosensory cortex of adult mice. These inputs primarily arise from functionally-interconnecting cortical areas and thalamic nuclei, illustrating that OPCs have strikingly comprehensive synaptic access to brain-wide projection networks. Quantification of these inputs revealed excitatory and inhibitory components that are consistent in number across brain regions and stable in barrel cortex despite whisker trimming-induced sensory deprivation.

The projection of anorectal afferents to cortex of the rat: Comparison of two methods of cortical mapping.

BACKGROUND: The rat has served usefully as a model for fecal incontinence and exploration of the mechanism of action of sacral neuromodulation. However, there is a gap in knowledge concerning representation(s) on the primary sensory cortex of this anatomical region. METHODS: Multi-electrode array (32 channels) and intrinsic optical signal (IOS) processing were used to map cortical activation sites following anorectal electrical stimulation in the rat. A simple method for expanding a 32-electrode array to a virtual 2700 array was refined. KEY RESULTS: The IOS method identified activation of parietal cortex following anorectal or first sacral nerve root (S1) stimulation; however, the signal was poorly localized and large spontaneous vasomotion was observed in pial vessels. In contrast, the resulting high-density maps showed two anatomically distinct cortical activation sites to anorectal stimulation. CONCLUSIONS & INFERENCES: There are two distinct sites of activation on the parietal cortex following anorectal stimulation in the rat. The implications for sacral neuromodulation as a therapy for fecal incontinence are discussed.

Cortical Organization of Centrifugal Afferents to the Olfactory Bulb: Mono- and Trans-synaptic Tracing with Recombinant Neurotropic Viral Tracers.

Sensory processing is strongly modulated by different brain and behavioral states, and this is based on the top-down modulation. In the olfactory system, local neural circuits in the olfactory bulb (OB) are innervated by centrifugal afferents in order to regulate the processing of olfactory information in the OB under different behavioral states. The purpose of the present study was to explore the organization of neural networks in olfactory-related cortices and modulatory nuclei that give rise to direct and indirect innervations to the glomerular layer (GL) of the OB at the whole-brain scale. Injection of different recombinant attenuated neurotropic viruses into the GL showed that it received direct inputs from each layer in the OB, centrifugal inputs from the ipsilateralanterior olfactory nucleus (AON), anterior piriform cortex (Pir), and horizontal limb of diagonal band of Broca (HDB), and various indirect inputs from bilateral cortical neurons in the AON, Pir, amygdala, entorhinal cortex, hippocampus, HDB, dorsal raphe, median raphe and locus coeruleus. These results provide a circuitry basis that will help further understand the mechanism by which olfactory information-processing in the OB is regulated.

Tracing of Afferent Connections in the Zebrafish Cerebellum Using Recombinant Rabies Virus.

The cerebellum is involved in some forms of motor coordination and learning, and in cognitive and emotional functions. To elucidate the functions of the cerebellum, it is important to unravel the detailed connections of the cerebellar neurons. Although the cerebellar neural circuit structure is generally conserved among vertebrates, it is not clear whether the cerebellum receives and processes the same or similar information in different vertebrate species. Here, we performed monosynaptic retrograde tracing with recombinant rabies viruses (RV) to identify the afferent connections of the zebrafish cerebellar neurons. We used a G-deleted RV that expressed GFP. The virus was also pseudotyped with EnvA, an envelope protein of avian sarcoma and leucosis virus (ALSV-A). For the specific infection of cerebellar neurons, we expressed the RV glycoprotein (G) gene and the envelope protein TVA, which is the receptor for EnvA, in Purkinje cells (PCs) or granule cells (GCs), using the promoter for aldolase Ca (aldoca) or cerebellin 12 (cbln12), respectively. When the virus infected PCs in the aldoca line, GFP was detected in the PCs' presynaptic neurons, including GCs and neurons in the inferior olivary nuclei (IOs), which send climbing fibers (CFs). These observations validated the RV tracing method in zebrafish. When the virus infected GCs in the cbln12 line, GFP was again detected in their presynaptic neurons, including neurons in the pretectal nuclei, the nucleus lateralis valvulae (NLV), the central gray (CG), the medial octavolateralis nucleus (MON), and the descending octaval nucleus (DON). GFP was not observed in these neurons when the virus infected PCs in the aldoca line. These precerebellar neurons generally agree with those reported for other teleost species and are at least partly conserved with those in mammals. Our results demonstrate that the RV system can be used for connectome analyses in zebrafish, and provide fundamental information about the cerebellar neural circuits, which will be valuable for elucidating the functions of cerebellar neural circuits in zebrafish.

Selective targeting of unipolar brush cell subtypes by cerebellar mossy fibers.

In vestibular cerebellum, primary afferents carry signals from single vestibular end organs, whereas secondary afferents from vestibular nucleus carry integrated signals. Selective targeting of distinct mossy fibers determines how the cerebellum processes vestibular signals. We focused on vestibular projections to ON and OFF classes of unipolar brush cells (UBCs), which transform single mossy fiber signals into long-lasting excitation or inhibition respectively, and impact the activity of ensembles of granule cells. To determine whether these contacts are indeed selective, connectivity was traced back from UBC to specific ganglion cell, hair cell and vestibular organ subtypes in mice. We show that a specialized subset of primary afferents contacts ON UBCs, but not OFF UBCs, while secondary afferents contact both subtypes. Striking anatomical differences were observed between primary and secondary afferents, their synapses, and the UBCs they contact. Thus, each class of UBC functions to transform specific signals through distinct anatomical pathways.

Structural mapping with fiber tractography of the human cuneate fasciculus at microscopic resolution in cervical region.

Human spinal white matter tract anatomy has been mapped using post mortem histological information with the help of molecular tracing studies in animal models. This study used 7 Tesla diffusion MR tractography on a human cadaver that was harvested 24 hours post mortem to evaluate cuneate fasciculus anatomy in cervical spinal cord. Based on this method, for the first time much more nuanced tractographic anatomy was used to investigate possible new routes for cuneate fasciculus in the posterior and lateral funiculus. Additionally, current molecular tracing studies were reviewed, and confirmatory data was presented along with our radiological results. Both studies confirm that upon entry to the spinal cord, upper cervical level tracts (C1-2-3) travel inside lateral funiculus and lower level tracts travel medially inside the posterior funiculus after entry at posterolateral sulcus which is different than traditional knowledge of having cuneate fasciculus tracts concentrated in the lateral part of posterior funiculus.

Laterality of cerebellar afferent and efferent pathways in a healthy right-handed population: A diffusion tensor imaging study.

The cerebellum communicates with the cerebral cortex through the cortico-ponto-cerebellar tract (CPCT, cerebellar afferent) and the dentato-rubro-thalamo-cortical tract (DRTCT, cerebellar efferent). This study explored the laterality of CPCT and DRTCT in a right-handed population. Forty healthy right-handed subjects (18 males and 22 females with age range of 26-79 years old) who underwent diffusion tensor imaging (DTI) were retrospectively enrolled. Bilateral CPCT, DRTCT, and the corticospinal tract (CST) were reconstructed using probabilistic diffusion tensor tractography (DTT). Tract volume (TV) and fractional anisotropy (FA) were compared between dominant and non-dominant tracts. Subjects were divided into age groups (20-40, 41-60, and 61-80 years), and the DTI-derived parameters of the groups were compared to determine age-related differences. TV and FA of non-dominant CPCT were higher than those of dominant CPCT, and the dominant CST was higher than the non-dominant CST. The TV and FA of DRTCT showed no side-to-side difference. The 61-80 years age group had the highest TV of the dominant and non-dominant DRTCT among the three groups and the highest FA of the non-dominant CPCT and DRTCT. The results revealed the structural characteristics of CPCT and DRTCT using probabilistic DTT. Normal asymmetric patterns and age-related changes in cerebellar white matter tracts may be important to researchers investigating cerebro-cerebellar structural connectivity.

Human Motor Thalamus Reconstructed in 3D from Continuous Sagittal Sections with Identified Subcortical Afferent Territories.

Classification and delineation of the motor-related nuclei in the human thalamus have been the focus of numerous discussions for a long time. Difficulties in finding consensus have for the most part been caused by paucity of direct experimental data on connections of individual nuclear entities. Kultas-Ilinsky et al. (2011) showed that distribution of glutamic acid decarboxylase isoform 65 (GAD65), the enzyme that synthesizes inhibitory neurotransmitter γ-aminobutyric acid, is a reliable marker that allows to delineate connectionally distinct nuclei in the human motor thalamus, namely the territories innervated by nigral, pallidal, and cerebellar afferents. We compared those immunocytochemical staining patterns with underlying cytoarchitecture and used the latter to outline the three afferent territories in a continuous series of sagittal Nissl-stained sections of the human thalamus. The 3D volume reconstructed from the outlines was placed in the Talairach stereotactic coordinate system relative to the intercommissural line and sectioned in three stereotactic planes to produce color-coded nuclear maps. This 3D coordinate-based atlas was coregistered to the Montreal Neurological Institute (MNI-152) space. The current report proposes a simplified nomenclature of the motor-related thalamic nuclei, presents images of selected histological sections and stereotactic maps illustrating topographic relationships of these nuclei as well as their relationship with adjacent somatosensory afferent region. The data are useful in different applications such as functional MRI and diffusion tractography. The 3D dataset is publicly available under an open license and can also be applicable in clinical interventions in the thalamus.

The Changing Sensory and Sympathetic Innervation of the Young, Adult and Aging Mouse Femur.

Although bone is continually being remodeled and ultimately declines with aging, little is known whether similar changes occur in the sensory and sympathetic nerve fibers that innervate bone. Here, immunohistochemistry and confocal microscopy were used to examine changes in the sensory and sympathetic nerve fibers that innervate the young (10 days post-partum), adult (3 months) and aging (24 months) C57Bl/6 mouse femur. In all three ages examined, the periosteum was the most densely innervated bone compartment. With aging, the total number of sensory and sympathetic nerve fibers clearly declines as the cambium layer of the periosteum dramatically thins. Yet even in the aging femur, there remains a dense sensory and sympathetic innervation of the periosteum. In cortical bone, sensory and sympathetic nerve fibers are largely confined to vascularized Haversian canals and while there is no significant decline in the density of sensory fibers, there was a 75% reduction in sympathetic nerve fibers in the aging vs. adult cortical bone. In contrast, in the bone marrow the overall density/unit area of both sensory and sympathetic nerve fibers appeared to remain largely unchanged across the lifespan. The preferential preservation of sensory nerve fibers suggests that even as bone itself undergoes a marked decline with age, the nociceptors that detect injury and signal skeletal pain remain relatively intact.

Neuronal Regression of Internal Leg Vibroreceptor Organs in a Cave-Dwelling Insect (Orthoptera: Rhaphidophoridae: Dolichopoda araneiformis).

Animals' adaptations to cave habitats generally include elaboration of extraoptic senses, and in insects the receptor structures located on the legs are supposed to become more prominent in response to constant darkness. The receptors for detecting substrate vibrations are often highly sensitive scolopidial sensilla localized within the legs or the body. For troglobitic insects the evolutionary changes in vibroreceptor organs have not been studied. Since rock is an extremely unfavorable medium for vibration transmission, selection on vibration receptors may be weakened in caves, and these sensory organs may undergo regressive evolution. We investigated the anatomy of the most elaborate internal vibration detection system in orthopteroid insects, the scolopidial subgenual organ complex in the cave cricket Dolichopoda araneiformis (Orthoptera: Ensifera: Rhaphidophoridae). This is a suitable model species which shows high levels of adaptation to cave life in terms of both phenotypic and life cycle characteristics. We compared our data with data on the anatomy and physiology of the subgenual organ complex from the related troglophilic species Troglophilus neglectus. In D. araneiformis, the subgenual organ complex contains three scolopidial organs: the subgenual organ, the intermediate organ, and the accessory organ. The presence of individual organs and their innervation pattern are identical to those found in T. neglectus, while the subgenual organ and the accessory organ of D. araneiformis contain about 50% fewer scolopidial sensilla than in T. neglectus. This suggests neuronal regression of these organs in D. araneiformis, which may reflect a relaxed selection pressure for vibration detection in caves. At the same time, a high level of overall neuroanatomical conservation of the intermediate organ in this species suggests persistence of the selection pressure maintaining this particular organ. While regressive evolution of chordotonal organs has been documented for insect auditory organs, this study shows for the first time that internal vibroreceptors can also be affected.

Anterior and posterior parts of the rat ventral tegmental area and the rostromedial tegmental nucleus receive topographically distinct afferents from the lateral habenular complex.

That activation of the reward system involves increased activity of dopaminergic (DA) neurons in the ventral tegmental area (VTA) is widely accepted. In contrast, the lateral habenular complex (LHb), which is known as the center of the anti-reward system, directly and indirectly inhibits DA neurons in the VTA. The VTA, however, is not a homogenous entity. Instead, it displays major functional differences between its anterior (aVTA) and posterior (pVTA) regions. It is not precisely known, whether habenular input to the aVTA, pVTA, and the newly recognized rostromedial tegmental nucleus (RMTg) are similarly or differently organized. Consequently, the present investigation addressed the connections between LHb and aVTA, pVTA, and RMTg using retrograde and anterograde tracing techniques in the rat. Our experiments disclosed strictly reciprocal and conspicuously focal interconnections between LHbM (LHbMPc/LHbMC) and PN, as well as between RLi and LHbLO. In addition, we found that LHb inputs to the aVTA are dorsoventrally ordered. Dorsal parts of the aVTA receive afferents from LHbL and LHbM, whereas ventral parts of the aVTA are preferentially targeted by the LHbM. LHb afferents to the pVTA are distinct from those to the RMTg, given that the RMTg is primarily innervated from the LHbL, whereas pVTA receives afferents from LHbM and LHbL. These data indicate the existence of two separate pathways from the LHb to the VTA, a direct and an indirect one, which may subserve distinct biological functions.

Afferent and efferent connections of the interpeduncular nucleus with special reference to circuits involving the habenula and raphe nuclei.

The habenula is an epithalamic structure differentiated into two nuclear complexes, medial (MHb) and lateral habenula (LHb). Recently, MHb together with its primary target, the interpeduncular nucleus (IP), have been identified as major players in mediating the aversive effects of nicotine. However, structures downstream of the MHb-IP axis, including the median (MnR) and caudal dorsal raphe nucleus (DRC), may contribute to the behavioral effects of nicotine. The afferent and efferent connections of the IP have hitherto not been systematically investigated with sensitive tracers. Thus, we placed injections of retrograde or anterograde tracers into different IP subdivisions or the MnR and additionally examined the transmitter phenotype of major IP and MnR afferents by combining retrograde tract tracing with immunofluorescence and in situ hybridization techniques. Besides receiving inputs from MHb and also LHb, we found that IP is reciprocally interconnected mainly with midline structures, including the MnR/DRC, nucleus incertus, supramammillary nucleus, septum, and laterodorsal tegmental nucleus. The bidirectional connections between IP and MnR proved to be primarily GABAergic. Regarding a possible topography of IP outputs, all IP subnuclei gave rise to descending projections, whereas major ascending projections, including focal projections to ventral hippocampus, ventrolateral septum, and LHb originated from the dorsocaudal IP. Our findings indicate that IP is closely associated to a distributed network of midline structures that modulate hippocampal theta activity and forms a node linking MHb and LHb with this network, and the hippocampus. Moreover, they support a cardinal role of GABAergic IP/MnR interconnections in the behavioral response to nicotine.

Orthogonal topography in the parallel input architecture of songbird HVC.

Neural activity within the cortical premotor nucleus HVC (acronym is name) encodes the learned songs of adult male zebra finches (Taeniopygia guttata). HVC activity is driven and/or modulated by a group of five afferent nuclei (the Medial Magnocellular nucleus of the Anterior Nidopallium, MMAN; Nucleus Interface, NIf; nucleus Avalanche, Av; the Robust nucleus of the Arcopallium, RA; the Uvaeform nucleus, Uva). While earlier evidence suggested that HVC receives a uniformly distributed and nontopographic pattern of afferent input, recent evidence suggests this view is incorrect (Basista et al., ). Here, we used a double-labeling strategy (varying both the distance between and the axial orientation of dual tracer injections into HVC) to reveal a massively parallel and in some cases topographic pattern of afferent input. Afferent neurons target only one rostral or caudal location within medial or lateral HVC, and each HVC location receives convergent input from each afferent nucleus in parallel. Quantifying the distributions of single-labeled cells revealed an orthogonal topography in the organization of afferent input from MMAN and NIf, two cortical nuclei necessary for song learning. MMAN input is organized across the lateral-medial axis whereas NIf input is organized across the rostral-caudal axis. To the extent that HVC activity is influenced by afferent input during the learning, perception, or production of song, functional models of HVC activity may need revision to account for the parallel input architecture of HVC, along with the orthogonal input topography of MMAN and NIf.

Transformation of spatiotemporal dynamics in the macaque vestibular system from otolith afferents to cortex.

Sensory signals undergo substantial recoding when neural activity is relayed from sensors through pre-thalamic and thalamic nuclei to cortex. To explore how temporal dynamics and directional tuning are sculpted in hierarchical vestibular circuits, we compared responses of macaque otolith afferents with neurons in the vestibular and cerebellar nuclei, as well as five cortical areas, to identical three-dimensional translational motion. We demonstrate a remarkable spatio-temporal transformation: otolith afferents carry spatially aligned cosine-tuned translational acceleration and jerk signals. In contrast, brainstem and cerebellar neurons exhibit non-linear, mixed selectivity for translational velocity, acceleration, jerk and position. Furthermore, these components often show dissimilar spatial tuning. Moderate further transformation of translation signals occurs in the cortex, such that similar spatio-temporal properties are found in multiple cortical areas. These results suggest that the first synapse represents a key processing element in vestibular pathways, robustly shaping how self-motion is represented in central vestibular circuits and cortical areas.

Whole-brain mapping of afferent projections to the bed nucleus of the stria terminalis in tree shrews.

The bed nucleus of the stria terminalis (BST) plays an important role in integrating and relaying input information to other brain regions in response to stress. The cytoarchitecture of the BST in tree shrews (Tupaia belangeri chinensis) has been comprehensively described in our previous publications. However, the inputs to the BST have not been described in previous reports. The aim of the present study was to investigate the sources of afferent projections to the BST throughout the brain of tree shrews using the retrograde tracer Fluoro-Gold (FG). The present results provide the first detailed whole-brain mapping of BST-projecting neurons in the tree shrew brain. The BST was densely innervated by the prefrontal cortex, entorhinal cortex, ventral subiculum, amygdala, ventral tegmental area, and parabrachial nucleus. Moreover, moderate projections to the BST originated from the medial preoptic area, supramammillary nucleus, paraventricular thalamic nucleus, pedunculopontine tegmental nucleus, dorsal raphe nucleus, locus coeruleus, and nucleus of the solitary tract. Afferent projections to the BST are identified in the ventral pallidum, nucleus of the diagonal band, ventral posteromedial thalamic nucleus, posterior complex of the thalamus, interfascicular nucleus, retrorubral field, rhabdoid nucleus, intermediate reticular nucleus, and parvicellular reticular nucleus. In addition, the different densities of BST-projecting neurons in various regions were analyzed in the tree shrew brains. In summary, whole-brain mapping of direct inputs to the BST is delineated in tree shrews. These brain circuits are implicated in the regulation of numerous physiological and behavioral processes including stress, reward, food intake, and arousal.