Rostrocaudal Axis Research Articles

Aging But Not Age-Related Hearing Loss Dominates the Decrease of Parvalbumin Immunoreactivity in the Primary Auditory Cortex of Mice.

Alterations in inhibitory circuits of the primary auditory cortex (pAC) have been shown to be an aspect of aging and age-related hearing loss (AHL). Several studies reported a decline in parvalbumin (PV) immunoreactivity in aged rodent pAC of animals displaying AHL and conclude a relationship between reduced sensitivity and declined PV immunoreactivity. However, it remains elusive whether AHL or a general molecular aging is causative for decreased PV immunoreactivity. In this study, we aimed to disentangle the effects of AHL and general aging on PV immunoreactivity patterns in inhibitory interneurons of mouse pAC. We compared young and old animals of a mouse line with AHL (C57BL/6) and a mutant (C57B6.CAST-Cdh23Ahl+) that is not vulnerable to AHL according to their hearing status by measuring auditory brainstem responses (ABRs) and by an immunohistochemical evaluation of the PV immunoreactivity patterns in two dimensions (rostro-caudal and layer) in the pAC. Although AHL could be confirmed by ABR measurements for the C57BL/6 mice, both aged strains showed a similar reduction of PV+ positive interneurons in both, number and density. The pattern of reduction across the rostro-caudal axis and across cortical layers was similar for both aged lines. Our results demonstrate that a reduced PV immunoreactivity is a sign of general, molecular aging and not related to AHL.

Morbidity in the postoperative follow-up of endoscopic anterior skull base surgery

IntroductionEndoscopic access to the sellar region by videoendoscopy shows a low rate of surgical complications, with findings that indicate risk factors for reducing morbidities during and after the postoperative period. ObjectiveTo evaluate, over a nine-year period, the acquisition of skills by the anterior skull base surgical team, according to the time of elimination of nasal crusts and/or the presence of morbidities in the postoperative follow-up of individuals treated in a tertiary public hospital. MethodsAfter confirming the diagnosis of skull base pathologies, the individuals in this study underwent endoscopic surgery according to the rostrocaudal or coronal axis. For the skull base reconstruction, the nasoseptal flap (associated or not with fascia lata with thigh fat) or free graft was used; clinical follow-up of individuals occurred for a minimum period of 12 months. To assess the impact of the surgical approach on patient clinical evolution, qualitative data related to smoking, post-nasal discharge, nasal flow, smell, taste, clinical symptoms of headache, cranial paresthesia, comorbidities and postoperative morbidities were obtained. ResultsThe most frequent diagnosis was pituitary macroadenoma (84.14%). The mean absence of crusts in this cohort was 124.45 days (confidence interval 95%=119.50–129.39). There was a low cerebrospinal fluid fistula rate (3%). Reconstruction with the nasoseptal flap with a fat graft was an independent variable that recorded the highest mean time for the elimination of nasal crusts (=145 days, confidence interval 95%=127.32–162.68). Allergic rhinitis and smoking were shown to be the most important and independent variables that increased the mean time to eliminate nasal crusts. ConclusionThe mean time to eliminate nasal crusts did not change over the years during which the procedures were performed, demonstrating the adequate training of the surgical team. Debridement and nasal irrigation with saline solutions should be performed more frequently and effectively in patients with allergic rhinitis, smokers and those who received the nasoseptal flap and fascia lata graft with autologous fat.

Sensory nerve endings arising from single spinal afferent neurons that innervate both circular muscle and myenteric ganglia in mouse colon: colon-brain axis.

There is considerable interest in understanding how contents within the gut wall (including microbiome) can activate sensory nerve endings in the gut that project to the central nervous system. However, we have only recently begun to understand the location and characteristics of extrinsic spinal afferent nerve endings that innervate the lower gastrointestinal (GI) tract. Our aim is to identify the nerve endings in the mouse distal colon that arise from single spinal afferent neurons. C57BL/6 mice were anaesthetised and single dorsal root ganglia (DRG) between lumbosacral L6-S1 were injected with dextran biotin. Mice recovered for 7days. Animals were then euthanized and whole colons removed, fixed and stained for calcitonin-gene-related-peptide (CGRP). Single spinal afferent nerve axons were identified entering the distal colon that ramified along many rows of myenteric ganglia, often giving rise to varicose nerve endings. These same axons bifurcated in the circular muscle giving rise to 4-5 groups of branching-type intramuscular endings, where each group of endings was separated by ~ 370μm in the rostro-caudal axis and projected 1.2mm around the circumference. As spinal afferent axons bifurcated, their axons often showed dramatic reductions in diameter. Here, we identified in the distal colon, the characteristics of nerve endings that arise from single colorectal-projecting axons with cell bodies in DRG. These findings suggest that a population of sensory neurons in DRG can potentially detect sensory stimuli simultaneously via different morphological types of endings that lie in both colonic smooth muscle and myenteric ganglia.

Propagating Motor Cortical Dynamics Facilitate Movement Initiation

Voluntary movement initiation involves the modulations of large groups of neurons in the primary motor cortex (M1). Yet similar modulations occur during movement planning when no movement occurs. Here, we show that a sequential spatiotemporal pattern of excitability propagates across M1 prior to the movement initiation in one of two oppositely oriented directions along the rostro-caudal axis. Using spatiotemporal patterns of intracortical microstimulation, we find that reaction time increases significantly when stimulation is delivered against, but not with, the natural propagation direction. Functional connections among M1 units emerge at movement that are oriented along the same rostro-caudal axis but not during movement planning. Finally, we show that beta amplitude profiles can more accurately decode muscle activity when they conform to the natural propagating patterns. These findings provide the first causal evidence that large-scale, propagating patterns of cortical excitability are behaviorally relevant and may be a necessary component of movement initiation.

Morphological alterations of the reticular thalamic nucleus in Engrailed-2 knockout mice.

The reticular thalamic nucleus (Rt) is a sheet of neurons that surrounds the dorsal thalamus laterally, along its dorso-ventral and rostro-caudal axes. It consists of inhibitory neurons releasing gamma-aminobutyric acid (GABA). This nucleus participates in the circuitry between the thalamus and the cerebral cortex, and its impairment is associated with neuro-psychiatric disorders. In this study, we investigated the Rt anatomy of Engrailed-2 knockout mice (En2-/- ), a mouse model of autism spectrum disorder (ASD), using parvalbumin as an immunohistochemical marker. We compared 4- and 6-week-old wild type (WT) and En2-/- mice using various morphometric parameters: cell area, shape factor, circularity and cell density. Significant differences were present in 6-week-old male mice with different genetic background (WT vs. En2-/- ): the Rt neurons of En2-/- mice showed a bigger cell area, shape factor and circularity when compared with WT. Age (4weeks vs. 6weeks) influenced the shape factor of WT females, the circularity and cell density of En2-/- males, and the shape factor and circularity of En2-/- females. Gender affected cell density in 4-week-old WT mice, shape factor and cellularity of 6-week-old WT mice, and cell area, shape factor and cell density of En2-/- at 6weeks. Intrasubject (left-right) asymmetry of Rt was never observed. These results show for the first time that sex- and age-related changes occur in the Rt GABAergic neurons of the En2-/- ASD mouse model.

Walking on chains: the morphology and mechanics behind the fin ray derived limbs of sea-robins.

Fish fin rays (lepidotrichia) are typically composed of paired and segmented flexible structures (hemitrichia) that help support and change the shape of the fins to affect water flow. Yet, marine ray-finned fish that are members of the family Priontinae (sea-robins) have specialized pectoral fin rays that are separated from the fin and used as limbs to walk along the seafloor. While previous kinematic studies have demonstrated the use of these specialized fin rays as walking appendages, there is little information on how the morphology of the 'walking rays' and associated musculature facilitate underwater walking. Here, we examine the musculoskeletal anatomy of the walking and pectoral fin rays in the striped sea-robin Prionotus evolans and compare the mechanical properties of the rays with those of the smaller northern sea-robin Prionotus carolinus We aimed to determine what structural modifications in the walking rays allow them to function as a supportive limb. We found enlarged processes for muscle attachment, bone extensions that brace the hemitrich articulations, and reduced flexibility and increased second moment of area along the rostro-caudal bending axis in the rays used for walking. This novel limb design may have promoted the benthic foraging behavior exhibited by these species by uncoupling locomotion and feeding.

Diversity of neurogenic smooth muscle electrical rhythmicity in mouse proximal colon.

The mechanisms underlying electrical rhythmicity in smooth muscle of the proximal colon are incompletely understood. Our aim was to identify patterns of electrical rhythmicity in smooth muscle of the proximal region of isolated whole mouse colon and characterize their mechanisms of origin. Two independent extracellular recording electrodes were used to record the patterns of electrical activity in smooth muscle of the proximal region of whole isolated mouse colon. Cross-correlation analysis was used to quantify spatial coordination of these electrical activities over increasing electrode separation distances. Four distinct neurogenic patterns of electrical rhythmicity were identified in smooth muscle of the proximal colon, three of which have not been identified and consisted of bursts of rhythmic action potentials at 1-2 Hz that were abolished by hexamethonium. These neurogenic patterns of electrical rhythmicity in smooth muscle were spatially and temporally synchronized over large separation distances (≥2 mm rosto-caudal axis). Myogenic slow waves could be recorded from the same preparations, but they showed poor spatial and temporal coordination over even short distances (≤1 mm rostro-caudal axis). It is not commonly thought that electrical rhythmicity in gastrointestinal smooth muscle is dependent upon the enteric nervous system. Here, we identified neurogenic patterns of electrical rhythmicity in smooth muscle of the proximal region of isolated mouse colon, which are dependent on synaptic transmission in the enteric nervous system. If the whole colon is studied in vitro, recordings can preserve novel neurogenic patterns of electrical rhythmicity in smooth muscle.NEW & NOTEWORTHY Previously, it has not often been thought that electrical rhythmicity in smooth muscle of the gastrointestinal tract is dependent upon the enteric nervous system. We identified patterns of electrical rhythmicity in smooth muscle of the mouse proximal colon that were abolished by hexamethonium and involved the temporal synchronization of smooth muscle membrane potential over large spatial fields. We reveal different patterns of electrical rhythmicity in colonic smooth muscle that are dependent on the ENS.

Functional architecture underlying binocular coordination of eye position and velocity in the larval zebrafish hindbrain

BackgroundThe oculomotor integrator (OI) in the vertebrate hindbrain transforms eye velocity input into persistent position coding output, which plays a crucial role in retinal image stability. For a mechanistic understanding of the integrator function and eye position control, knowledge about the tuning of the OI and other oculomotor nuclei is needed. Zebrafish are increasingly used to study integrator function and sensorimotor circuits, yet the precise neuronal tuning to motor variables remains uncharacterized.ResultsHere, we recorded cellular calcium signals while evoking monocular and binocular optokinetic eye movements at different slow-phase eye velocities. Our analysis reveals the anatomical distributions of motoneurons and internuclear neurons in the nucleus abducens as well as those of oculomotor neurons in caudally adjacent hindbrain volumes. Each neuron is tuned to eye position and/or velocity to variable extents and is only activated after surpassing particular eye position and velocity thresholds. While the abducens (rhombomeres 5/6) mainly codes for eye position, in rhombomeres 7/8, a velocity-to-position coding gradient exists along the rostro-caudal axis, which likely corresponds to the oculomotor structures storing velocity and position, and is in agreement with a feedforward mechanism of persistent activity generation. Position encoding neurons are recruited at eye position thresholds distributed across the behaviourally relevant dynamic range, while velocity-encoding neurons have more centred firing thresholds for velocity. In the abducens, neurons coding exclusively for one eye intermingle with neurons coding for both eyes. Many of these binocular neurons are preferentially active during conjugate eye movements and less active during monocular eye movements. This differential recruitment during monocular versus conjugate tasks represents a functional diversification in the final common motor pathway.ConclusionsWe localized and functionally characterized the repertoire of oculomotor neurons in the zebrafish hindbrain. Our findings provide evidence for a mixed but task-specific binocular code and suggest that generation of persistent activity is organized along the rostro-caudal axis in the hindbrain.

Assessment of degenerative cervical stenosis on T2-weighted MR imaging: sensitivity to change and reliability of mid-sagittal and axial plane metrics.

A retrospective cross-sectional study. To assess the sensitivity to change and reliability of various mid-sagittal and axial plane metrics in the assessment of patients with single-level degenerative cervical stenosis on T2-weighted MR imaging. A diagnostic MR imaging facility in Sydney (Australia). We retrospectively reviewed T2-weighted MR images of 85 consecutive patients (48 M and 37 F) with single-level degenerative cervical stenosis. Canal compromise and cord compression were evaluated using three mid-sagittal plane metrics (M1, M2, and M3) and two axial plane metrics (M4 and M5), at the level of stenosis and nonstenotic cephalad and caudal levels (controls). Sensitivity to change (SC) for each metric was evaluated as the percentage deviation of the measured value from the estimated normal value based on cephalad and caudal controls. Reliability for each metric was evaluated using intraclass correlation coefficients. Degenerative cervical stenosis showed a bimodal distribution peaking at C5-6 (n = 32) and C3-4 (n = 29) levels. The changes in the canal and cord geometry along the rostrocaudal axis were inconsistent. Across all individual subjects (reflecting a range of stenosis severity), M3 (-32.87% ± 10.60%) was more sensitive to change compared with M1 (16.64% ± 16.48%) and M2 (-23.95% ± 11.12%). Similarly, M4 (-24.62% ± 12.17%) was more sensitive to change compared with M5 (-6.71% ± 11.08%). The level of reliability was "moderate" to "excellent" for mid-sagittal plane measurements, and "poor" to "excellent" for axial plane measurements. Changes in canal dimensions in the mid-sagittal plane and cord shape in the axial plane are sensitive indicators of degenerative cervical stenosis on T2-weighted MR images.

Skilled Movements in Mice Require Inhibition of Corticospinal Axon Collateral Formation in the Spinal Cord by Semaphorin Signaling.

Corticospinal (CS) neurons in layer V of the sensorimotor cortex are essential for voluntary motor control. Those neurons project axons to specific segments along the rostro-caudal axis of the spinal cord, and reach their spinal targets by sending collateral branches interstitially along axon bundles. Currently, little is known how CS axon collaterals are formed in the proper spinal cord regions. Here, we show that the semaphorin3A (Sema3A)-neuropilin-1 (Npn-1) signaling pathway is an essential negative regulator of CS axon collateral formation in the spinal cord from mice of either sex. Sema3A is expressed in the ventral spinal cord, whereas CS neurons express Npn-1, suggesting that Sema3A might prevent CS axons from entering the ventral spinal cord. Indeed, the ectopic expression of Sema3A in the spinal cord in vivo inhibits CS axon collateral formation, whereas Sema3A or Npn-1 mutant mice have ectopic CS axon collateral formation within the ventral spinal cord compared with littermate controls. Finally, Npn-1 mutant mice exhibit impaired skilled movements, likely because of aberrantly formed CS connections in the ventral spinal cord. These genetic findings reveal that Sema3A-Npn-1 signaling-mediated inhibition of CS axon collateral formation is critical for proper CS circuit formation and the ability to perform skilled motor behaviors.SIGNIFICANCE STATEMENT CS neurons project axons to the spinal cord to control skilled movements in mammals. Previous studies revealed some of the molecular mechanisms underlying different phases of CS circuit development such as initial axon guidance in the brain, and midline crossing in the brainstem and spinal cord. However, the molecular mechanisms underlying CS axon collateral formation in the spinal gray matter has remained obscure. In this study, using in vivo gain-of- and loss-of-function experiments, we show that Sema3A-Npn-1 signaling functions to inhibit CS axon collateral formation in the ventral spinal cord, allowing for the development of proper skilled movements in mice.

Enhancing surface coil sensitive volume with hybridized electric dipoles at 17.2 T.

Preclinical MR applications at 17.2 T can require field of views on the order of a few square centimeters. This is a challenging task as the proton Larmor frequency reaches 730 MHz. Most of the protocols at such frequencies are performed with surface transceiver coils for which the sensitive volume and the signal to noise ratio (SNR) is given by their size. Here we propose an approach based on metamaterials in order to enhance the sensitive volume of a commercial surface coil for small animal imaging at 17.2 T. We designed a passive resonator composed of four hybridized electric dipoles placed onto the floor of the MRI bed. Combining numerical and experimental results on a phantom and in vivo, we demonstrate a 20% increase of the sensitive volume in depth and 25% along the rostro-caudal axis while maintaining more than 85% of the local SNR right beneath the surface coil plane. Moreover, our solution gives the ability to double the average SNR in the region between 1.2 and 2 cm away from the loop using a single layer of 1 mm thick metallic wires easy to design and manufacture.

Inferring Regulatory Programs Governing Region Specificity of Neuroepithelial Stem Cells during Early Hindbrain and Spinal Cord Development.

Neuroepithelial stem cells (NSC) from different anatomical regions of the embryonic neural tube's rostrocaudal axis can differentiate into diverse central nervous system tissues, but the transcriptional regulatory networks governing these processes are incompletely understood. Here, we measure region-specific NSC gene expression along the rostrocaudal axis in a human pluripotent stem cell model of early central nervous system development over a 72-h time course, spanning the hindbrain to cervical spinal cord. We introduce Escarole, a probabilistic clustering algorithm for non-stationary time series, and combine it with prior-based regulatory network inference to identify genes that are regulated dynamically and predict their upstream regulators. We identify known regulators of patterning and neural development, including the HOX genes, and predict a direct regulatory connection between the transcription factor POU3F2 and target gene STMN2. We demonstrate that POU3F2 is required for expression of STMN2, suggesting that this regulatory connection is important for region specificity of NSCs.

Vocal fold scars: a common classification proposal by the American Laryngological Association and European Laryngological Society.

Vocal fold scar is one the most challenging benign laryngeal pathologies. The purpose of this paper is to propose a classification that will allow for a common description of this entity between laryngologists, prevent discrepancies in interpretation, allow for comparison of related studies, and offer a training tool for young laryngologists. Based on the depth and laterality of scarring, we propose 4 types: type I, characterized by atrophy of lamina propria with/without affected epithelium; type II, where the epithelium, lamina propria, and muscle are affected; type III, where the scar is located on the anterior commissure; type IV, which includes extended scar formation in both anteroposterior and rostro-caudal axis with significant loss of vocal fold mass. We believe that our proposal is comprehensive and encompasses all existing iatrogenic and non-iatrogenic etiologies in a simple and concise manner. It also serves its purpose as a descriptive, comparative, and training tool.

Distribution of D1 and D2 receptor- immunoreactive neurons in the paraventricular nucleus of the hypothalamus in the rat

The paraventricular nucleus (PVN) of the hypothalamus is an important center in regulating the functions of internal organs, and it is the key nucleus for coordinating endocrine, behavior and autonomic stress responses. Dopamine receptors are widely expressed in the hypothalamus and participate in the regulation of many vital activities, such as blood pressure and glycolipid metabolism, but the details of the cellular localization of dopamine receptors in the PVN are not clear. The present study investigated the distribution of D1 and D2 receptor-immunoreactive (IR) neurons in the subnuclei of the PVN and their co-labeling with vasopressin (VP) and oxytocin (OT) in rats by means of Nissl staining and immunofluorescence. The PVN is subdivided into magnocellular and parvicellular subnuclei. The results showed that the D1 receptor-IR neurons were primarily located in the magnocellular subnuclei and distributed throughout several regions of the PVN, including the paraventricular hypothalamic nucleus, lateral magnocellular part (PaLM), medial magnocellular part (PaMM) and posterior part (PaPO). Additionally, the neurons co-labeled with OT and VP. D2 receptor-IR neurons had a distribution pattern similar to that of D1 receptors. The D1- and D2-IR neurons in the subnuclei of the PVN were in relatively close proximity to the fornix. Several subnuclei gradually shifted from the ventral medial aspect of the fornix to the dorsal side when examined along the rostrocaudal axis. In summary, D1 and D2 receptors are widely distributed in the subnuclei of PVN in a similar distribution pattern with a slightly less number of D2 receptor immunoreactive neurons than that of D1. Moreover, D1 and D2 receptors are coexisted with VP and OT. The present study provides important morphological evidence for the function of dopamine receptors in the PVN.

A blueprint of mammalian cortical connectomes.

The cerebral cortex of mammals exhibits intricate interareal wiring. Moreover, mammalian cortices differ vastly in size, cytological composition, and phylogenetic distance. Given such complexity and pronounced species differences, it is a considerable challenge to decipher organizational principles of mammalian connectomes. Here, we demonstrate species-specific and species-general unifying principles linking the physical, cytological, and connectional dimensions of architecture in the mouse, cat, marmoset, and macaque monkey. The existence of connections is related to the cytology of cortical areas, in addition to the role of physical distance, but this relation is attenuated in mice and marmoset monkeys. The cytoarchitectonic cortical gradients, and not the rostrocaudal axis of the cortex, are closely linked to the laminar origin of connections, a principle that allows the extrapolation of this connectional feature to humans. Lastly, a network core, with a central role under different modes of network communication, characterizes all cortical connectomes. We observe a displacement of the network core in mammals, with a shift of the core of cats and macaque monkeys toward the less neuronally dense areas of the cerebral cortex. This displacement has functional ramifications but also entails a potential increased degree of vulnerability to pathology. In sum, our results sketch out a blueprint of mammalian connectomes consisting of species-specific and species-general links between the connectional, physical, and cytological dimensions of the cerebral cortex, possibly reflecting variations and persistence of evolutionarily conserved mechanisms and cellular phenomena. Our framework elucidates organizational principles that encompass but also extend beyond the wiring economy principle imposed by the physical embedding of the cerebral cortex.

Stem-Cell-Driven Growth and Regrowth of the Adult Spinal Cord in Teleost Fish.

The spinal cord of the teleost fish Apteronotus leptorhynchus continues to grow during adulthood, in concert with the overall body growth. Immunohistological studies, combined with mathematical modeling, suggest that this growth is driven by proliferative activity of Sox2-expressing stem/progenitor cells (SPCs) and by cell drift due to population pressure. The SPCs exhibit high volumetric density in the caudal filament and the ependymal layer. Nevertheless, the majority of these cells are found in the parenchyma throughout the rostro-caudal axis of the spinal cord, albeit at much lower volumetric densities than in the ependymal layer. The SPCs give rise, via transit-amplifying cells, to neurons and glia. The relative number of neurons and glia is primarily regulated through apoptosis of supernumerary neurons. Quantitative analysis has demonstrated that the continued cell proliferation results in additive neurogenesis. This addition includes adult-born spinal electromotoneurons, thereby resulting in a continuous increase in the amplitude of the fish's electric organ discharge during adult life. Amputation of the caudal part of the spinal cord induces initially a degenerative response, dominated by massive apoptotic cell death in spinal cord tissue immediately rostral to the injury site, and distinguished by a partial loss of the electric organ discharge amplitude. This phase is followed by a regenerative response, characterized by absence of gliosis and by rapid stem-cell-driven tissue regrowth. Although the quality of the regenerated tissue is variable among individuals, the structural repair has led in every fish examined thus far to full recovery of the electric organ discharge amplitude.

The Claustrum of the Pig: An Immunohistochemical and a Quantitative Golgi Study.

Despite increasing interest in the claustrum (Cl) over the last decades, its function is still a puzzling problem. Among the experimental species of potential use in Cl research, the pig is considered an interesting model, because of the similarities of its brain with the corresponding cortical and subcortical human structures. The swine Cl presents a peculiar morphology, characterized by a wide posterior enlargement, ideal for physiological investigations. There is a wealth of data on general anatomy, cytoarchitecture, and chemo architecture of the Cl, but much less is known about the dendritic morphometry of its neurons. Dendritic length and branching pattern are key features to understand the organization of the microcircuitry, and thus the delineation of the structure-function relationships of the Cl. To this effect, we undertook (a) a quantitative study of the dendrites of the spiny neurons of the swine Cl, employing the Golgi staining; and (b) an immunohistochemical analysis to describe the distribution of the parvalbumin (PV)-immunoreactive interneurons throughout the same nucleus. Taken together, the results that we report here show that the dendritic architecture and the distribution of the PV expressing interneurons change when the Cl of this species changes its shape along the rostro-caudal axis, thus suggesting a potentially specific function for the large posterior puddle. Anat Rec, 302:1638-1646, 2019. © 2019 American Association for Anatomy.

Rostrocaudal subregions of the ventral tegmental area are differentially impacted by chronic stress.

The ventral tegmental area (VTA) is implicated in the pathophysiology of depression and addictive disorders and is subject to the detrimental effects of stress. Chronic stress may differentially alter the activity pattern of its different subregions along the rostrocaudal and dorsoventral axes, which may relate to the variable behavioral sensitivity to stress mediated by these subregions. Here, chronic stress-exposed rats were tested for depressive-like reactivity. In situ hybridization for zif268 as a marker of neuronal activation was combined with in vivo single-unit recording of dopaminergic neurons to assess modifications in the activity of the rostral VTA (rVTA) and caudal VTA (cVTA). Changes in the expression of stress-responsiveglucocorticoid receptors (GR) and brain-derived neurotrophic factor (BDNF) were also assessed. Stress-induced anhedonia-like, hyper-anxious, and passive-like responding were associated with reductions in dopaminergic burst activity in the cVTA and an increase in local GABAergic activity, particularly in GABAA receptor sensitivity. On the other hand, stress increased single-spiking activity, burst activity, and zif268 mRNA levels in the rVTA, which were associated with increased glutamatergic tonus and enhanced GR and AMPA receptor (AMPAR) expression. rVTA and cVTA activity differentially correlated with sucrose preference and passivity measures. These data demonstrate that the rVTA and cVTA respond differently to stress and suggest that while cVTA activity may be related to passivity-like states, the activity of both subregions appears to be related to anhedonia and the processing of incentive value. These region-dependent abnormalities indicate the multi-modular composition of the VTA, which could provide multiple substrates for different symptom features.

Motor context dominates output from purkinje cell functional regions during reflexive visuomotor behaviours.

The cerebellum integrates sensory stimuli and motor actions to enable smooth coordination and motor learning. Here we harness the innate behavioral repertoire of the larval zebrafish to characterize the spatiotemporal dynamics of feature coding across the entire Purkinje cell population during visual stimuli and the reflexive behaviors that they elicit. Population imaging reveals three spatially-clustered regions of Purkinje cell activity along the rostrocaudal axis. Complementary single-cell electrophysiological recordings assign these Purkinje cells to one of three functional phenotypes that encode a specific visual, and not motor, signal via complex spikes. In contrast, simple spike output of most Purkinje cells is strongly driven by motor-related tail and eye signals. Interactions between complex and simple spikes show heterogeneous modulation patterns across different Purkinje cells, which become temporally restricted during swimming episodes. Our findings reveal how sensorimotor information is encoded by individual Purkinje cells and organized into behavioral modules across the entire cerebellum.

Postnatal Development of NPY and Somatostatin-28 Peptidergic Populations in the Human Angular Bundle.

The angular bundle is a white matter fiber fascicle, which runs longitudinally along the parahippocampal gyrus. It is best known for carrying fibers from the entorhinal cortex (EC) to the hippocampus through the perforant and alvear pathways, as well as for carrying hippocampal output to the neocortex, and distributing fibers to polysensory cortex. The angular bundle is already present prenatally at the beginning of the fetal period. Connections between the EC and the hippocampus are established by the 20th gestational week (gw). In the postnatal period, it shows increasing myelination. The angular bundle, as well as other white matter portions of gyral surfaces in the brain, presents interstitial neurons, a remnant of subplate neurons. Those interstitial neurons show neurochemical phenotypes both prenatally and postnatally, among which, neuropeptide Y (NPY) and Somatostatin-28 (SOM-28) peptidergic populations are noticeable, and accompany the fiber connections in the maturation of the hippocampal formation. We sought to investigate the topography of the postnatal distribution and relative density of neurons immunoreactive for NPY or SOM in the angular bundle along the rostrocaudal axis of the hippocampus. The study was carried out in 15 cases, ranging from 35 gws, up to 14 year old. All cases showed positive neurons showing a polygonal or spindle shaped morphology for both peptides, scattered throughout the angular bundle. The highest number of positive neurons appeared around birth and the ensuing weeks. Up to one and a half years, the density of both peptidergic populations decreased slightly. However, cases older than 2 years of age showed a substantial decrease in density of immunolabeled neurons, density that did not showed a minor decrease in density of positive neurons in cases older than 2 years. In addition, a topography from caudal to rostral levels of the angular bundle was detected at all ages. The functional significance of interstitial cells is unknown, but the existence of SOM and NPY peptidergic neurons, presumably inhibitory, in the white matter of the angular bundle, could contribute to the basic wiring of the hippocampal formation, through which autobiographical and spatial memories can begin to be stored in the infant brain.