GABAC receptors in the lateral amygdala

A possible novel target for the treatment of fear and anxiety disorders?

Catarina Cunha, Marie H. Monfils, Joseph Ledoux

Research output: Contribution to journalArticle

Abstract

Activation of GABAARs in the lateral nucleus of the amygdala (LA), a key site of plasticity underlying fear learning, impairs fear learning. The role of GABACRs in the LA and other brain areas is poorly understood. GABACRs could be an important novel target for pharmacological treatments of anxiety-related disorders since, unlike GABAARs, GABACRs do not desensitize. To detect functional GABACRs in the LA we performed whole cell patch clamp recordings in vitro. We found that GABAARs and GABABRs blockade lead to a reduction of evoked inhibition and an increase increment of excitation, but activation of GABACRs caused elevations of evoked excitation, while blocking GABACRs reduced evoked excitation. Based on this evidence we tested whether GABACRs in LA contribute to fear learning in vivo. It is established that activation of GABAARs leads to blockage of fear learning. Application of GABAC drugs had a very different effect; fear learning was enhanced by activating and attenuated by blocking GABACRs in the LA. Our results suggest that GABAC and GABAARs play opposing roles in modulation of associative plasticity in LA neurons of rats. This novel role of GABACRs furthers our understanding of GABA receptors in fear memory acquisition and storage and suggests a possible novel target for the treatment of fear and anxiety disorders.

Original languageEnglish (US)
Article number6
JournalFrontiers in Behavioral Neuroscience
Volume4
Issue numberMAR
DOIs
StatePublished - Mar 12 2010

Fingerprint

Amygdala
Anxiety Disorders
Fear
Learning
GABA Receptors
GABA-C receptor
Pharmacology
Neurons
Brain
Pharmaceutical Preparations

Keywords

  • Fear learning memory
  • GABA
  • GABA receptors
  • Lateral amygdala
  • Muscimol
  • PPD
  • TPMPA

ASJC Scopus subject areas

  • Behavioral Neuroscience
  • Cognitive Neuroscience
  • Neuropsychology and Physiological Psychology

Cite this

GABAC receptors in the lateral amygdala : A possible novel target for the treatment of fear and anxiety disorders? / Cunha, Catarina; Monfils, Marie H.; Ledoux, Joseph.

In: Frontiers in Behavioral Neuroscience, Vol. 4, No. MAR, 6, 12.03.2010.

Research output: Contribution to journalArticle

@article{adc43222608442c1bad3704a3b611ffd,
title = "GABAC receptors in the lateral amygdala: A possible novel target for the treatment of fear and anxiety disorders?",
abstract = "Activation of GABAARs in the lateral nucleus of the amygdala (LA), a key site of plasticity underlying fear learning, impairs fear learning. The role of GABACRs in the LA and other brain areas is poorly understood. GABACRs could be an important novel target for pharmacological treatments of anxiety-related disorders since, unlike GABAARs, GABACRs do not desensitize. To detect functional GABACRs in the LA we performed whole cell patch clamp recordings in vitro. We found that GABAARs and GABABRs blockade lead to a reduction of evoked inhibition and an increase increment of excitation, but activation of GABACRs caused elevations of evoked excitation, while blocking GABACRs reduced evoked excitation. Based on this evidence we tested whether GABACRs in LA contribute to fear learning in vivo. It is established that activation of GABAARs leads to blockage of fear learning. Application of GABAC drugs had a very different effect; fear learning was enhanced by activating and attenuated by blocking GABACRs in the LA. Our results suggest that GABAC and GABAARs play opposing roles in modulation of associative plasticity in LA neurons of rats. This novel role of GABACRs furthers our understanding of GABA receptors in fear memory acquisition and storage and suggests a possible novel target for the treatment of fear and anxiety disorders.",
keywords = "Fear learning memory, GABA, GABA receptors, Lateral amygdala, Muscimol, PPD, TPMPA",
author = "Catarina Cunha and Monfils, {Marie H.} and Joseph Ledoux",
year = "2010",
month = "3",
day = "12",
doi = "10.3389/neuro.08.006.2010",
language = "English (US)",
volume = "4",
journal = "Frontiers in Behavioral Neuroscience",
issn = "1662-5153",
publisher = "Frontiers Research Foundation",
number = "MAR",

}

TY - JOUR

T1 - GABAC receptors in the lateral amygdala

T2 - A possible novel target for the treatment of fear and anxiety disorders?

AU - Cunha, Catarina

AU - Monfils, Marie H.

AU - Ledoux, Joseph

PY - 2010/3/12

Y1 - 2010/3/12

N2 - Activation of GABAARs in the lateral nucleus of the amygdala (LA), a key site of plasticity underlying fear learning, impairs fear learning. The role of GABACRs in the LA and other brain areas is poorly understood. GABACRs could be an important novel target for pharmacological treatments of anxiety-related disorders since, unlike GABAARs, GABACRs do not desensitize. To detect functional GABACRs in the LA we performed whole cell patch clamp recordings in vitro. We found that GABAARs and GABABRs blockade lead to a reduction of evoked inhibition and an increase increment of excitation, but activation of GABACRs caused elevations of evoked excitation, while blocking GABACRs reduced evoked excitation. Based on this evidence we tested whether GABACRs in LA contribute to fear learning in vivo. It is established that activation of GABAARs leads to blockage of fear learning. Application of GABAC drugs had a very different effect; fear learning was enhanced by activating and attenuated by blocking GABACRs in the LA. Our results suggest that GABAC and GABAARs play opposing roles in modulation of associative plasticity in LA neurons of rats. This novel role of GABACRs furthers our understanding of GABA receptors in fear memory acquisition and storage and suggests a possible novel target for the treatment of fear and anxiety disorders.

AB - Activation of GABAARs in the lateral nucleus of the amygdala (LA), a key site of plasticity underlying fear learning, impairs fear learning. The role of GABACRs in the LA and other brain areas is poorly understood. GABACRs could be an important novel target for pharmacological treatments of anxiety-related disorders since, unlike GABAARs, GABACRs do not desensitize. To detect functional GABACRs in the LA we performed whole cell patch clamp recordings in vitro. We found that GABAARs and GABABRs blockade lead to a reduction of evoked inhibition and an increase increment of excitation, but activation of GABACRs caused elevations of evoked excitation, while blocking GABACRs reduced evoked excitation. Based on this evidence we tested whether GABACRs in LA contribute to fear learning in vivo. It is established that activation of GABAARs leads to blockage of fear learning. Application of GABAC drugs had a very different effect; fear learning was enhanced by activating and attenuated by blocking GABACRs in the LA. Our results suggest that GABAC and GABAARs play opposing roles in modulation of associative plasticity in LA neurons of rats. This novel role of GABACRs furthers our understanding of GABA receptors in fear memory acquisition and storage and suggests a possible novel target for the treatment of fear and anxiety disorders.

KW - Fear learning memory

KW - GABA

KW - GABA receptors

KW - Lateral amygdala

KW - Muscimol

KW - PPD

KW - TPMPA

UR - http://www.scopus.com/inward/record.url?scp=78651504961&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=78651504961&partnerID=8YFLogxK

U2 - 10.3389/neuro.08.006.2010

DO - 10.3389/neuro.08.006.2010

M3 - Article

VL - 4

JO - Frontiers in Behavioral Neuroscience

JF - Frontiers in Behavioral Neuroscience

SN - 1662-5153

IS - MAR

M1 - 6

ER -