Organizational principles of amygdalar input-output neuronal circuits

Limeng Huang,J Julius Zhu,Wei Gong,Li Lin,Yiwen Chen,Shumin Duan,Sen Jin,Ke Si

doi:10.1038/s41380-021-01262-3

Abstract

The amygdala, one of the most studied brain structures, integrates brain-wide heterogeneous inputs and governs multidimensional outputs to control diverse behaviors central to survival, yet how amygdalar input-output neuronal circuits are organized remains unclear. Using a simplified cell-type- and projection-specific retrograde transsynaptic tracing technique, we scrutinized brain-wide afferent inputs of four major output neuronal groups in the amygdalar basolateral complex (BLA) that project to the bed nucleus of the stria terminals (BNST), ventral hippocampus (vHPC), medial prefrontal cortex (mPFC) and nucleus accumbens (NAc), respectively. Brain-wide input-output quantitative analysis unveils that BLA efferent neurons receive a diverse array of afferents with varied input weights and predominant contextual representation. Notably, the afferents received by BNST-, vHPC-, mPFC- and NAc-projecting BLA neurons exhibit virtually identical origins and input weights. These results indicate that the organization of amygdalar BLA input-output neuronal circuits follows the input-dependent and output-independent principles, ideal for integrating brain-wide diverse afferent stimuli to control parallel efferent actions. The data provide the objective basis for improving the virtual reality exposure therapy for anxiety disorders and validate the simplified cell-type- and projection-specific retrograde transsynaptic tracing method.

Highlights

The amygdala, an evolutionarily conserved brain structure, has been intensively examined due to its involvement in a large set of survival behaviors and psychiatric conditions [1,2,3]
Our results showed that ~5% output basolateral complex (BLA) neurons sent collateralizations to two targeting areas (Fig. 2B, C), suggesting output bed nucleus of the stria terminals (BNST), ventral hippocampus (vHPC), medial prefrontal cortex (mPFC)- and nucleus accumbens (NAc)-projecting BLA neurons to be largely independent groups with small numbers of neurons projecting to multiple brain areas
The amygdala sends efferent signals to multiple brain areas to orchestrate defensive behaviors, and the main amygdalar output pathways seem to go through BNST, vHPC, mPFC and NAc to control initiation, acquisition, evaluation and decision-making of survival behaviors, respectively [1, 6]

Summary

Introduction

The amygdala, an evolutionarily conserved brain structure, has been intensively examined due to its involvement in a large set of survival behaviors and psychiatric conditions [1,2,3]. A collective work over the last 70 years has mapped the extensive afferent and efferent connections of the amygdala [4,5,6] These data indicate that the amygdala integrates brain-wide diverse afferent stimuli, including sensory, integrative, contextual, neuromodulatory and other miscellaneous inputs. Due to the lack of quantitative and correlative analysis of the brain-wide amygdalar afferent and efferent connections [1], how amygdalar input-output neuronal circuits are organized to transform diverse afferent stimuli into multiple efferent signals to govern survival behaviors remains unclear. BNST-, vHPC-, mPFC- and NAc-projecting BLA neurons receive the brain-wide afferents with virtually identical origins and input weights. The amygdalar BLA afferent and efferent patterns immediately suggest an input-dependent and output-independent anatomical organizational design, which seems to be ideal for integrating brain-wide diverse afferent stimuli to control parallel efferent behavioral actions

Methods

Results

Conclusion