Synaptic transmission changes in fear memory circuits underlie key features of an animal model of schizophrenia

Marie Pollard, Christophe Varin, Brian Hrupka, Darrel J. Pemberton, Thomas Steckler, Hamdy Shaban

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Non-competitive antagonists of the N-methyl-d-aspartate receptor (NMDA) such as phencyclidine (PCP) elicit schizophrenia-like symptoms in healthy individuals. Similarly, PCP dosing in rats produces typical behavioral phenotypes that mimic human schizophrenia symptoms. Although schizophrenic behavioral phenotypes of the PCP model have been extensively studied, the underlying alterations of intrinsic neuronal properties and synaptic transmission in relevant limbic brain microcircuits remain elusive. Acute brain slice electrophysiology and immunostaining of inhibitory neurons were used to identify neuronal circuit alterations of the amygdala and hippocampus associated with changes in extinction of fear learning in rats following PCP treatment. Subchronic PCP application led to impaired long-term potentiation (LTP) and marked increases in the ratio of NMDA to 2-amino-3(5-methyl-3-oxo-1,2-oxazol-4-yl)propionic acid (AMPA) receptor-mediated currents at lateral amygdala (LA) principal neurons without alterations in parvalbumin (PV) as well as non-PV, glutamic acid decarboxylase 67 (GAD 67) immunopositive neurons. In addition, LTP was impaired at the Schaffer collateral to CA1 hippocampal pathway coincident with a reduction in colocalized PV and GAD67 immunopositive neurons in the CA3 hippocampal area. These effects occurred without changes in spontaneous events or intrinsic membrane properties of principal cells in the LA. The impairment of LTP at both amygdalar and hippocampal microcircuits, which play a key role in processing relevant survival information such as fear and extinction memory concurred with a disruption of extinction learning of fear conditioned responses. Our results show that subchronic PCP administration in rats impairs synaptic functioning in the amygdala and hippocampus as well as processing of fear-related memories.

Original languageEnglish
Pages (from-to)184-193
Number of pages10
JournalBehavioural Brain Research
Volume227
Issue number1
DOIs
Publication statusPublished - Feb 1 2012
Externally publishedYes

Fingerprint

Amygdala
Synaptic Transmission
Fear
Long-Term Potentiation
Schizophrenia
Animal Models
Neurons
Parvalbumins
Hippocampus
Learning
Phenotype
Phencyclidine
Glutamate Decarboxylase
AMPA Receptors
Electrophysiology
Brain
Membranes
Survival
Psychological Extinction
aspartic acid receptor

Keywords

  • Amygdala
  • Extinction
  • LTP
  • NMDA
  • Parvalbumin
  • Phencyclidine

ASJC Scopus subject areas

  • Behavioral Neuroscience

Cite this

Synaptic transmission changes in fear memory circuits underlie key features of an animal model of schizophrenia. / Pollard, Marie; Varin, Christophe; Hrupka, Brian; Pemberton, Darrel J.; Steckler, Thomas; Shaban, Hamdy.

In: Behavioural Brain Research, Vol. 227, No. 1, 01.02.2012, p. 184-193.

Research output: Contribution to journalArticle

Pollard, Marie ; Varin, Christophe ; Hrupka, Brian ; Pemberton, Darrel J. ; Steckler, Thomas ; Shaban, Hamdy. / Synaptic transmission changes in fear memory circuits underlie key features of an animal model of schizophrenia. In: Behavioural Brain Research. 2012 ; Vol. 227, No. 1. pp. 184-193.
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