Extensive and spatially variable within-cell-type heterogeneity across the basolateral amygdala.

Timothy P O'Leary,Andrew L Lemire,Jody Clements,Kaitlin E Sullivan,Mark S Cembrowski,Lihua Wang

doi:10.7554/elife.59003

Timothy P O'Leary, Andrew L Lemire + Show 4 more

Open Access

https://doi.org/10.7554/elife.59003

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Abstract

The basolateral amygdala complex (BLA), extensively connected with both local amygdalar nuclei as well as long-range circuits, is involved in a diverse array of functional roles. Understanding the mechanisms of such functional diversity will be greatly informed by understanding the cell-type-specific landscape of the BLA. Here, beginning with single-cell RNA sequencing, we identified both discrete and graded continuous gene-expression differences within the mouse BLA. Via in situ hybridization, we next mapped this discrete transcriptomic heterogeneity onto a sharp spatial border between the basal and lateral amygdala nuclei, and identified continuous spatial gene-expression gradients within each of these regions. These discrete and continuous spatial transformations of transcriptomic cell-type identity were recapitulated by local morphology as well as long-range connectivity. Thus, BLA excitatory neurons are a highly heterogenous collection of neurons that spatially covary in molecular, cellular, and circuit properties. This heterogeneity likely drives pronounced spatial variation in BLA computation and function.

Highlights

The amygdala is a brain region that governs a variety of functions and behaviors (Janak and Tye, 2015)
The amygdala has been studied for the role it plays in acquisition and expression of conditioned fear memory (Fanselow and LeDoux, 1999; Maren and Quirk, 2004), with more recent evidence implicating this brain region to be involved in other aversive states like anxiety (Daviu et al, 2019)
We identified a precipitous decline in the cell body size of auditory cortex (ACX)-projecting neurons, relative to projections from the ventral hippocampus (VHC), medial entorhinal cortex (MEC), prefrontal cortex (PFC), nucleus accumbens (NAC) and retrosplenial cortex (RSC) (p

Summary

Introduction

The amygdala is a brain region that governs a variety of functions and behaviors (Janak and Tye, 2015). The basolateral amygdala complex (BLA) is one region that has received particular attention, in large part due to its high degree of reciprocal long-range connectivity with other brain regions (Amir et al, 2018; Janak and Tye, 2015; Little and Carter, 2013; McGarry and Carter, 2017; Senn et al, 2014) This anatomical arrangement suggests a powerful role for the BLA in orchestrating a variety of long-range computations, and enables circuit-specific experimental access for mapping circuits onto function and behavior (Tovote et al, 2015). To facilitate use of our data as a resource for future studies, we have created a web-based portal to allow easy access and analysis of the scRNA-seq data in our study (http://scrnaseq.janelia.org/amygdala; schematic: Figure 1)

Results

Discussion

Materials and methods