Activation of the same mGluR5 receptors in the amygdala causes divergent effects on specific versus indiscriminate fear.

Mohammed Mostafizur Rahman,Sumantra Chattarji,Giselle Fernandes,Sonal Kedia

doi:10.7554/elife.25665

Abstract

Although mGluR5-antagonists prevent fear and anxiety, little is known about how the same receptor in the amygdala gives rise to both. Combining in vitro and in vivo activation of mGluR5 in rats, we identify specific changes in intrinsic excitability and synaptic plasticity in basolateral amygdala neurons that give rise to temporally distinct and mutually exclusive effects on fear-related behaviors. The immediate impact of mGluR5 activation is to produce anxiety manifested as indiscriminate fear of both tone and context. Surprisingly, this state does not interfere with the proper encoding of tone-shock associations that eventually lead to enhanced cue-specific fear. These results provide a new framework for dissecting the functional impact of amygdalar mGluR-plasticity on fear versus anxiety in health and disease.

Highlights

The group I metabotropic glutamate receptor subtype mGluR5 in the amygdala plays an important role in conditioned fear and anxiety-like behavior
We examined the effects of DHPG on AMPAR-mediated spontaneous excitatory postsynaptic currents, as well as miniature excitatory postsynaptic currents
The findings reported here provide new insights into how activation of the same mGluR5 receptor can modulate intrinsic excitability and synaptic plasticity in neurons of the basolateral amygdala (BLA), thereby leading to distinct effects on specific versus indiscriminate fear

Summary

Introduction

The group I metabotropic glutamate receptor subtype mGluR5 in the amygdala plays an important role in conditioned fear and anxiety-like behavior. Intra-amygdaloid microinjections of the same antagonist prevents anxiety in a variety of rodent models (La Mora et al, 2006) Consistent with these animal studies, mGluR5 antagonists have been reported to act as effective anxiolytics in human conditions of fear and anxiety (Porter et al, 2005). A complementary experimental strategy, involving selective activation of the same receptor, may offer a way of dissecting the neuronal basis of these two amygdala-dependent behaviors. This line of investigation remains largely unexplored in the amygdala, as much of our current understanding is based primarily on studies that used systemic administration of mGluR5 antagonists to modulate these behaviors in rodents (Swanson et al, 2005)

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Conclusion