Perturbation of GABAergic synapses at the axon initial segment of basolateral amygdala induces trans-regional metaplasticity at the medial prefrontal cortex

Rinki Saha, Kuldeep Shrivastava, Liang Jing, Rachel Schayek, Mouna Maroun, Martin Kriebel, Hansjürgen Volkmer, Gal Richter-Levin

Research output: Contribution to journalArticlepeer-review

Abstract

GABAergic synapses in the basolateral amygdala (BLA) play an important role in fear memory generation. We have previously reported that reduction in GABAergic synapses innervating specifically at the axon initial segment (AIS) of principal neurons of BLA, by neurofascin (NF) knockdown, impairs fear extinction. BLA is bidirectionally connected with the medial prefrontal cortex (mPFC), which is a key region involved in extinction of acquired fear memory. Here, we showed that reducing AIS GABAergic synapses within the BLA leads to impairment of synaptic plasticity in the BLA-mPFC pathway, as well as in the ventral subiculum (vSub)-mPFC pathway, which is independent of BLA involvement. The results suggest that the alteration within the BLA subsequently resulted in a form of trans-regional metaplasticity in the mPFC. In support of that notion, we observed that NF knockdown induced a severe deficit in behavioral flexibility as measured by reversal learning. Interestingly, reversal learning similar to extinction learning is an mPFC-dependent behavior. In agreement with that, measurement of the immediate-early gene, c-Fos immunoreactivity after reversal learning was reduced in the mPFC and BLA, supporting further the notion that the BLA GABAergic manipulation resulted in trans-regional metaplastic alterations within the mPFC.

Original languageEnglish
Pages (from-to)395-410
Number of pages16
JournalCerebral Cortex
Volume28
Issue number1
DOIs
StatePublished - 1 Jan 2018

Bibliographical note

Publisher Copyright:
© The Author 2017.

Keywords

  • Amygdala
  • Medial prefrontal cortex
  • Metaplasticity
  • Neurofascin
  • Reversal learning

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Cognitive Neuroscience

Fingerprint

Dive into the research topics of 'Perturbation of GABAergic synapses at the axon initial segment of basolateral amygdala induces trans-regional metaplasticity at the medial prefrontal cortex'. Together they form a unique fingerprint.

Cite this