Vaughn, E. | Search bioRxiv

bioRxiv2022

Three-dimensional Interrogation of Cell Types and Instinctive Behavior in the Periaqueductal Gray

The periaqueductal gray (PAG) is a critical midbrain hub that relays information from the forebrain to motor and autonomic brainstem centers to orchestrate instinctive behaviors. The current organization of the PAG into four main radial columns lacks the resolution needed to account for the vast range of PAG functions. Using spatially resolved single-cell transcriptomic measurements, we uncovered widespread transcriptional heterogeneity in the PAG with >100 excitatory and inhibitory neuronal populations, which further assemble into 19 spatial metaclusters. We explored the transcriptional and spatial logic of PAG function during instinctive behaviors and demonstrated the regional recruitment of cell types for distinct behaviors. Unexpectedly, certain behaviors trigger differential spatial activation patterns within given cell types, illustrating the complexity of PAG molecular and functional 3D organization. The newly uncovered spatial motifs and high precision cellular map of instinctive behavior in the PAG open new avenues for a mechanistic understanding of PAG function.

neuroscience↗

bioRxiv2019

Molecular and Circuit Architecture of Social Hierarchy

Social hierarchy is a common organizational structure of animal groups, in which an individuals social status generates an adaptive behavioral state that facilitates interactions with other group members. Although generally stable, the social status of an animal can change, underscoring the plasticity of the underlying neural circuits. Here, we uncover the molecular and biophysical properties of a cortico-thalamic circuit that supports the emergence of hierarchy in mice. We established a robust behavioral paradigm to explore the establishment of hierarchy among groups of unfamiliar males, and identified the mediodorsal thalamus (MDT) and the caudal part of anterior cingulate area (cACC) as brain areas that are differentially activated between dominants and subordinates. Glutamatergic MDT neurons project to inhibitory parvalbumin interneurons of the cACC, and activity levels of both cell types control competitive performance. Synaptic inputs and excitability of MDT neurons undergo dramatic changes according to the animal social status, and single nucleus sequencing identified increased transcription of the voltage gated ion channel Trpm3 in dominant mice, leading to enhanced excitatory transmission in the MDT-cACC circuit. Our data suggest a model in which cellular, molecular and biophysical plasticity in a thalamocortical circuit controls the expression of social status.

neuroscience↗