scholarly journals GABAergic neurons in the olfactory cortex projecting to the lateral hypothalamus in mice

2018 ◽  
Author(s):  
Koshi Murata ◽  
Tomoki Kinoshita ◽  
Yugo Fukazawa ◽  
Kenta Kobayashi ◽  
Kazuto Kobayashi ◽  
...  
Keyword(s):  
Olfactory Bulb ◽  
Lateral Hypothalamus ◽  
Ventral Striatum ◽  
Glutamate Transporter ◽  
Olfactory Cortex ◽  
Acid Decarboxylase ◽  
Projection Neurons ◽  
Diagonal Band ◽  
Glutamate Transporter 1 ◽  
Glutamic Acid Decarboxylase 65

AbstractOlfaction guides goal-directed behaviours including feeding. To investigate how central olfactory neural circuits control feeding behaviour in mice, we performed retrograde tracing from the lateral hypothalamus (LH), an important feeding centre. We observed a cluster of retrogradely labelled cells distributed in the posteroventral region of the olfactory peduncle. Histochemical analyses revealed that a majority of these retrogradely labelled projection neurons expressed glutamic acid decarboxylase 65/67 (GAD65/67), but not vesicular glutamate transporter 1 (VGluT1). We named this region with GABAergic projection neurons the ventral olfactory nucleus (VON) to discriminate it from the conventional olfactory peduncle. VON neurons were less immunoreactive for DARPP-32, a striatal neuron marker, in comparison to those in the olfactory tubercle and nucleus accumbens, which distinguished the VON from the ventral striatum. Fluorescent labelling confirmed synaptic contacts between VON neurons and olfactory bulb projection neurons. Rabies-virus-mediated trans-synaptic labelling revealed that VON neurons received synaptic inputs from the olfactory bulb, other olfactory cortices, horizontal limb of the diagonal band, and prefrontal cortex. Collectively, these results identified novel GABAergic projection neurons in the olfactory cortex that can integrate olfactory sensory and top-down inputs and send inhibitory output to the LH, which may contribute to forming odour-guided LH-related behaviours.

scholarly journals Altered dopaminergic pathways and therapeutic effects of intranasal dopamine in two distinct mouse models of autism

2020 ◽  
Author(s):  
Owen Y Chao ◽  
Salil S Pathak ◽  
Hao Zhang ◽  
Nathan Dunaway ◽  
Jay-Shake Li ◽  
...  
Keyword(s):  
Fragile X ◽  
Glutamate Transporter ◽  
Dorsal Striatum ◽  
Autism Spectrum ◽  
Acid Decarboxylase ◽  
Therapeutic Effects ◽  
Spatial Coupling ◽  
Motivated Behavior ◽  
Object Based ◽  
Glutamate Transporter 1

Abstract The dopamine (DA) system has a profound impact on reward-motivated behavior and is critically involved in neurodevelopmental disorders, such as autism spectrum disorder (ASD). Although DA defects are found in autistic patients, it is not well defined how the DA pathways are altered in ASD and whether DA can be utilized as a potential therapeutic agent for ASD. To this end, we employed a phenotypic and a genetic ASD model, i.e., Black and Tan BRachyury T+Itpr3tf/J (BTBR) mice and Fragile X Mental Retardation 1 knockout (Fmr1-KO) mice, respectively. Immunostaining of tyrosine hydroxylase (TH) to mark dopaminergic neurons revealed an overall reduction in the TH expression in the substantia nigra, ventral tegmental area and dorsal striatum of BTBR mice, as compared to C57BL/6J wild-type ones. In contrast, Fmr1-KO animals did not show such an alteration but displayed abnormal morphology of TH-positive axons in the striatum with higher “complexity” and lower “texture”. Both strains exhibited decreased expression of striatal dopamine transporter (DAT) and increased spatial coupling between vesicular glutamate transporter 1 (VGLUT1, a label for glutamatergic terminals) and TH signals, while GABAergic neurons quantified by glutamic acid decarboxylase 67 (GAD67) remained intact. Intranasal administration of DA rescued the deficits in non-selective attention, object-based attention and social approaching of BTBR mice, likely by enhancing the level of TH in the striatum. Application of intranasal DA to Fmr1-KO animals alleviated their impairment of social novelty, in association with reduced striatal TH protein. These results suggest that although the DA system is modified differently in the two ASD models, intranasal treatment with DA effectively rectifies their behavioral phenotypes, which may present a promising therapy for diverse types of ASD.

scholarly journals Glutamatergic Nonpyramidal Neurons From Neocortical Layer VI and Their Comparison With Pyramidal and Spiny Stellate Neurons

2009 ◽  
Vol 101 (2) ◽  
pp. 641-654 ◽  
Author(s):  
Sofija Andjelic ◽  
Thierry Gallopin ◽  
Bruno Cauli ◽  
Elisa L. Hill ◽  
Lisa Roux ◽  
...  
Keyword(s):  
Pyramidal Neurons ◽  
Glutamate Transporter ◽  
Gabaergic Interneuron ◽  
Acid Decarboxylase ◽  
Projection Neurons ◽  
Heterogeneous Cluster ◽  
Glutamatergic Neurons ◽  
Layer V ◽  
Nonpyramidal Neurons ◽  
Layer Vi

The deeper part of neocortical layer VI is dominated by nonpyramidal neurons, which lack a prominent vertically ascending dendrite and predominantly establish corticocortical connections. These neurons were studied in rat neocortical slices using patch-clamp, single-cell reverse transcription–polymerase chain reaction, and biocytin labeling. The majority of these neurons expressed the vesicular glutamate transporter but not glutamic acid decarboxylase, suggesting that a high proportion of layer VI nonpyramidal neurons are glutamatergic. Indeed, they exhibited numerous dendritic spines and established asymmetrical synapses. Our sample of glutamatergic nonpyramidal neurons displayed a wide variety of somatodendritic morphologies and a subset of these cells expressed the Nurr1 mRNA, a marker for ipsilateral, but not commissural corticocortical projection neurons in layer VI. Comparison with spiny stellate and pyramidal neurons from other layers showed that glutamatergic neurons consistently exhibited a low occurrence of GABAergic interneuron markers and regular spiking firing patterns. Analysis of electrophysiological diversity using unsupervised clustering disclosed three groups of cells. Layer V pyramidal neurons were segregated into a first group, whereas a second group consisted of a subpopulation of layer VI neurons exhibiting tonic firing. A third heterogeneous cluster comprised spiny stellate, layer II/III pyramidal, and layer VI neurons exhibiting adaptive firing. The segregation of layer VI neurons in two different clusters did not correlate either with their somatodendritic morphologies or with Nurr1 expression. Our results suggest that electrophysiological similarities between neocortical glutamatergic neurons extend beyond layer positioning, somatodendritic morphology, and projection specificity.

scholarly journals Prefrontal Cortex Regulates Chronic Stress-Induced Cardiovascular Susceptibility

2019 ◽  
Author(s):  
Derek Schaeuble ◽  
Amy E.B. Packard ◽  
Jessica M. McKlveen ◽  
Rachel L. Morano ◽  
Sarah Fourman ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Chronic Stress ◽  
Cardiovascular Health ◽  
Ex Vivo ◽  
Glutamate Release ◽  
Glutamate Transporter ◽  
Male Rats ◽  
Projection Neurons ◽  
Autonomic Imbalance ◽  
Glutamate Transporter 1

The medial prefrontal cortex (mPFC) is necessary for appropriate appraisal of stressful information, as well as coordinating visceral and behavioral processes. However, prolonged stress impairs mPFC function and prefrontal-dependent behaviors. Additionally, chronic stress induces sympathetic predominance, contributing to health detriments associated with autonomic imbalance. Previous studies identified a subregion of rodent prefrontal cortex, infralimbic cortex (IL), as a key regulator of neuroendocrine-autonomic integration after chronic stress, suggesting that IL output may prevent chronic stress-induced autonomic imbalance. In the current study, we tested the hypothesis that the IL regulates hemodynamic, vascular, and cardiac responses to chronic stress. To address this hypothesis, a viral-packaged siRNA construct was used to knockdown vesicular glutamate transporter 1 (vGluT1) and reduce glutamate packaging and release from IL projection neurons. Male rats were injected with a vGluT1 siRNA-expressing construct or GFP control into the IL and then remained as unstressed controls or were exposed to chronic variable stress (CVS). IL vGluT1 knockdown increased heart rate and mean arterial pressure (MAP) reactivity, while CVS increased chronic MAP only in siRNA-treated rats. In a separate cohort, CVS and vGluT1 knockdown interacted to impair both endothelial-dependent and endothelial-independent vasoreactivity ex vivo. Furthermore, vGluT1 knockdown and CVS increased histological markers of fibrosis and hypertrophy. Thus, knockdown of glutamate release from IL projection neurons indicates that these cells are necessary to prevent the enhanced sympathetic responses to stress that promote susceptibility to cardiovascular pathophysiology. These findings provide evidence for a neurobiological mechanism mediating the relationship between stress and poor cardiovascular health outcomes.

scholarly journals Altered dopaminergic pathways and therapeutic effects of intranasal dopamine in two distinct mouse models of autism

2020 ◽  
Author(s):  
Owen Y Chao ◽  
Salil S Pathak ◽  
Hao Zhang ◽  
Nathan Dunaway ◽  
Jay-Shake Li ◽  
...  
Keyword(s):  
Fragile X ◽  
Glutamate Transporter ◽  
Dorsal Striatum ◽  
Autism Spectrum ◽  
Acid Decarboxylase ◽  
Therapeutic Effects ◽  
Spatial Coupling ◽  
Motivated Behavior ◽  
Object Based ◽  
Glutamate Transporter 1

Abstract The dopamine (DA) system has a profound impact on reward-motivated behavior and is critically involved in neurodevelopmental disorders, such as autism spectrum disorder (ASD). Although DA defects are found in autistic patients, it is not well defined how the DA pathways are altered in ASD and whether DA can be utilized as a potential therapeutic agent for ASD. To this end, we employed a phenotypic and a genetic ASD model, i.e., Black and Tan BRachyury T + Itpr3 tf /J (BTBR) mice and Fragile X Mental Retardation 1 knockout ( Fmr1 -KO) mice, respectively. Immunostaining of tyrosine hydroxylase (TH) to mark dopaminergic neurons revealed an overall reduction in the TH expression in the substantia nigra, ventral tegmental area and dorsal striatum of BTBR mice, as compared to C57BL/6J wild-type ones. In contrast, Fmr1 -KO animals did not show such an alteration but displayed abnormal morphology of TH-positive axons in the striatum with higher “complexity” and lower “texture”. Both strains exhibited decreased expression of striatal dopamine transporter (DAT) and increased spatial coupling between vesicular glutamate transporter 1 (VGLUT1, a label for glutamatergic terminals) and TH signals, while GABAergic neurons quantified by glutamic acid decarboxylase 67 (GAD67) remained intact. Intranasal administration of DA rescued the deficits in non-selective attention, object-based attention and social approaching of BTBR mice, likely by enhancing the level of TH in the striatum. Application of intranasal DA to Fmr1- KO animals alleviated their impairment of social novelty, in association with reduced striatal TH protein. These results suggest that although the DA system is modified differently in the two ASD models, intranasal treatment with DA effectively rectifies their behavioral phenotypes, which may present a promising therapy for diverse types of ASD.

scholarly journals Molecular characterization of projection neuron subtypes in the mouse olfactory bulb

2020 ◽  
Author(s):  
Sara Zeppilli ◽  
Tobias Ackels ◽  
Robin Attey ◽  
Nell Klimpert ◽  
Kimberly D. Ritola ◽  
...  
Keyword(s):  
Olfactory Bulb ◽  
Projection Neuron ◽  
Mitral Cell ◽  
Olfactory Cortex ◽  
Cell Populations ◽  
Projection Neurons ◽  
Functional Roles ◽  
Entry Points ◽  
Single Nucleus ◽  
Tufted Cell

AbstractProjection neurons (PNs) in the mammalian olfactory bulb (OB) receive direct input from the nose and project to diverse cortical and subcortical areas. Morphological and physiological studies have highlighted functional heterogeneity, yet no molecular markers have been described that delineate PN subtypes. Here, we used viral injections into olfactory cortex and fluorescent nucleus sorting to enrich PNs for high-throughput single nucleus and bulk RNA deep sequencing. Transcriptome analysis and RNA in situ hybridization identified three mitral and five tufted cell populations with characteristic transcription factor network topology and cell adhesion and excitability-related gene expression. Finally, by integrating bulk and snRNA-seq data we propose that different mitral cell populations selectively project to different regions of olfactory cortex. Together, we have identified potential molecular and gene regulatory mechanisms underlying PN diversity and provide new molecular entry points into studying the diverse functional roles of mitral and tufted cell subtypes.

scholarly journals Neuronal BDNF Signaling Is Necessary for the Effects of Treadmill Exercise on Synaptic Stripping of Axotomized Motoneurons

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Joey Krakowiak ◽  
Caiyue Liu ◽  
Chandana Papudesu ◽  
P. Jillian Ward ◽  
Jennifer C. Wilhelm ◽  
...  
Keyword(s):  
Peripheral Nerve ◽  
Nerve Injury ◽  
Knockout Mice ◽  
Peripheral Nerve Injury ◽  
Treadmill Exercise ◽  
Glutamate Transporter ◽  
Acid Decarboxylase ◽  
Spinal Motoneurons ◽  
Synaptic Inputs ◽  
Glutamate Transporter 1

The withdrawal of synaptic inputs from the somata and proximal dendrites of spinal motoneurons following peripheral nerve injury could contribute to poor functional recovery. Decreased availability of neurotrophins to afferent terminals on axotomized motoneurons has been implicated as one cause of the withdrawal. No reduction in contacts made by synaptic inputs immunoreactive to the vesicular glutamate transporter 1 and glutamic acid decarboxylase 67 is noted on axotomized motoneurons if modest treadmill exercise, which stimulates the production of neurotrophins by spinal motoneurons, is applied after nerve injury. In conditional, neuron-specific brain-derived neurotrophic factor (BDNF) knockout mice, a reduction in synaptic contacts onto motoneurons was noted in intact animals which was similar in magnitude to that observed after nerve transection in wild-type controls. No further reduction in coverage was found if nerves were cut in knockout mice. Two weeks of moderate daily treadmill exercise following nerve injury in these BDNF knockout mice did not affect synaptic inputs onto motoneurons. Treadmill exercise has a profound effect on synaptic inputs to motoneurons after peripheral nerve injury which requires BDNF production by those postsynaptic cells.

scholarly journals Orexin-driven GAD65 network of the lateral hypothalamus sets physical activity in mice

2017 ◽  
Vol 114 (17) ◽  
pp. 4525-4530 ◽  
Author(s):  
Christin Kosse ◽  
Cornelia Schöne ◽  
Edward Bracey ◽  
Denis Burdakov
Keyword(s):  
Physical Activity ◽  
Lateral Hypothalamus ◽  
Physical Inactivity ◽  
Cell Activation ◽  
Cell Activity ◽  
Acid Decarboxylase ◽  
Cell Type ◽  
Cell Type Specific ◽  
Glutamic Acid Decarboxylase 65 ◽  
Deep Brain

Damage to the lateral hypothalamus (LH) causes profound physical inactivity in mammals. Several molecularly distinct types of LH neurons have been identified, including orexin cells and glutamic acid decarboxylase 65 (GAD65) cells, but their interplay in orchestrating physical activity is not fully understood. Here, using optogenetic circuit analysis and cell type-specific deep-brain recordings in behaving mice, we show that orexin cell activation rapidly recruits GAD65LH neurons. We demonstrate that internally initiated GAD65LH cell bursts precede and accompany spontaneous running bouts, that selective chemogenetic silencing of natural GAD65LH cell activity depresses voluntary locomotion, and that GAD65LH cell overactivation leads to hyperlocomotion. These results thus identify a molecularly distinct, orexin-activated LH submodule that governs physical activity in mice.

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