Functional organization of the midbrain periaqueductal gray for regulating aversive memory formation

Li-Feng Yeh,Joshua P Johansen,Takaaki Ozawa

doi:10.1186/s13041-021-00844-0

Abstract

Innately aversive experiences produce rapid defensive responses and powerful emotional memories. The midbrain periaqueductal gray (PAG) drives defensive behaviors through projections to brainstem motor control centers, but the PAG has also been implicated in aversive learning, receives information from aversive-signaling sensory systems and sends ascending projections to the thalamus as well as other forebrain structures which could control learning and memory. Here we sought to identify PAG subregions and cell types which instruct memory formation in response to aversive events. We found that optogenetic inhibition of neurons in the dorsolateral subregion of the PAG (dlPAG), but not the ventrolateral PAG (vlPAG), during an aversive event reduced memory formation. Furthermore, inhibition of a specific population of thalamus projecting dlPAG neurons projecting to the anterior paraventricular thalamus (aPVT) reduced aversive learning, but had no effect on the expression of previously learned defensive behaviors. By contrast, inactivation of dlPAG neurons which project to the posterior PVT (pPVT) or centromedial intralaminar thalamic nucleus (CM) had no effect on learning. These results reveal specific subregions and cell types within PAG responsible for its learning related functions.

Highlights

Aversive experiences produce immediate defensive behaviors and engage instructive circuits to trigger long lasting memories
We found that inactivation of dorsolateral PAG (dlPAG), but not ventrolateral PAG (vlPAG), neurons reduced the acquisition of aversive memories in animals that received laser inhibition during the shock period of fear conditioning (‘Overlap’ group) relative to control animals (Fig. 1C, D)
Having identified a specific dlPAG subregion important for aversive learning, we examined whether specific populations of dlPAG neurons which send axonal projection to thalamic regions are responsible for producing memory formation

Summary

Introduction

Aversive experiences produce immediate defensive behaviors and engage instructive circuits to trigger long lasting memories. The midbrain periaqueductal gray (PAG) coordinates defensive behavioral responses to innately and learned aversive events through afferent inputs from aversive sensory systems and forebrain regions like the amygdala and hypothalamus important for processing information related to learned and social threats [1,2,3,4]. While the role of the PAG in producing innate and learned defensive responses is well established, some studies suggest that the PAG participates in instructing learning in response to aversive stimuli during auditory fear conditioning [14,15,16]. Whether, and if so which, PAG projections to the thalamus are important in memory formation is not known

Methods

Results

Conclusion