Biology subjects

Vu, S.

Publications and source records attributed to Vu, S..

4 recordsLinked to original sources

bioRxiv2024

Multimodal classification of neurons in the lateral septum

The lateral septum (LS) is a ventral forebrain nucleus that modulates complex social and affective behaviors. These behaviors emerge from heterogeneous neuronal populations whose molecular identity and developmental origins remain poorly defined. We profiled the transcriptional identity of mature LS neurons derived from two progenitor lineages distinguished by their embryonic origin and Nkx2.1 expression history, identifying 22 molecularly distinct subtypes. Nkx2.1-lineage neurons are enriched for select cell adhesion and communication molecules; however, subtypes from distinct developmental origins can converge onto similar molecular profiles when residing within the same LS subregion. The graded expression of genes related to synaptic signaling is a primary axis defining the taxonomy of LS neurons. Using transcriptional markers, we labeled non-overlapping neuronal populations and characterized their connectivity, morphology, and electrophysiology. Together, these findings define the extent of LS neuronal diversity and provide a framework for understanding how complex behaviors are regulated by the LS.

neuroscience↗

bioRxiv2023

A developmentally defined population of neurons in the lateral septum controls responses to aversive stimuli

When interacting with their environment, animals must balance exploratory and defensive behavior to evaluate and respond to potential threats. The lateral septum (LS) is a structure in the ventral forebrain that calibrates the magnitude of behavioral responses to stress-related external stimuli, including the regulation of threat avoidance. The complex connectivity between the LS and other parts of the brain, together with its largely unexplored neuronal diversity, makes it difficult to understand how defined LS circuits control specific behaviors. Here, we describe a mouse model where the deletion of the transcriptional regulator Prdm16 in cells with a common developmental origin (Nkx2.1-lineage) results in the almost complete ablation of neurons from this lineage in the LS. Using a combination of single-nucleus RNA sequencing, histological and electrophysiological methods and behavioral analyses, we discovered that Crhr2-expresssing neurons are specifically affected in mutant mice, resulting in connectivity and electrophyisiological defects. This neuronal population is specifically activated in stressful contexts, and its removal results in increased exploratory behavior, even under stressful conditions. Our study extends the current knowledge about how defined neuronal populations within the LS can evaluate contextual information to select appropriate behavioral responses. This is a necessary step towards understanding the crucial role that the LS plays in neuropsychiatric conditions where defensive behavior is dysregulated, such as anxiety and aggression disorders.

neuroscience↗

bioRxiv2023

TRPV1 Opening is Stabilized Equally by Its Four Subunits

Capsaicin receptor TRPV1 is a nociceptor for vanilloid molecules such as capsaicin and resiniferatoxin (RTX). Even though cryo-EM structures of TRPV1 in complex with these molecules are available, how their binding energetically favors the open conformation is not known. Here we report an approach to control the number of bound RTX molecules (0-to-4) in functional mouse TRPV1. The approach allowed direct measurements of each of the intermediate open states under equilibrium conditions at both macroscopic and single-molecule levels. We found that RTX binding to each of the four subunits contributes virtually the same activation energy, which we estimated to be 1.86 kcal/mol and found to arise predominately from destabilizing the closed conformation. We further showed that sequential bindings of RTX increase open probability without altering single-channel conductance, confirming that there is likely a single open-pore conformation for TRPV1 activated by RTX.

biophysics↗

bioRxiv2020

Astrocyte-neuron crosstalk through Hedgehog signaling mediates cortical circuit assembly

Neuron-glia relationships play a critical role in the regulation of synapse formation and neuronal specification. The cellular and molecular mechanisms by which neurons and astrocytes communicate and coordinate are not well understood. Here we demonstrate that the canonical Sonic hedgehog (Shh) pathway is active in cortical astrocytes, where it acts to coordinate layer-specific synaptic connectivity and functional circuit development. We show that Ptch1 is a Shh receptor that is expressed by cortical astrocytes during development and that Shh signaling is necessary and sufficient to promote the expression of layer-specific astrocyte genes involved in regulating synapse formation and function. Loss of Shh in layer V neurons reduces astrocyte complexity and coverage by astrocytic processes in tripartite synapses, moreover, cell-autonomous activation of Shh signaling in astrocytes promotes cortical excitatory synapse formation. Together, these results suggest that Shh secreted from deep layer cortical neurons acts to specialize the molecular and functional features of astrocytes during development to shape circuit assembly and function.

neuroscience↗