Acute cognitive impairment after lateral fluid percussion brain injury recovers by 1 month: Evaluation by conditioned fear response

Jonathan Lifshitz, Brent M. Witgen, M. Sean Grady

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

Conditioned fear associates a contextual environment and cue stimulus to a foot shock in a single training trial, where fear expressed to the trained context or cue indicates cognitive performance. Lesion, aspiration or inactivation of the hippocampus and amygdala impair conditioned fear to the trained context and cue, respectively. Moreover, only bilateral experimental manipulations, in contrast to unilateral, abolish cognitive performance. In a model of unilateral brain injury, we sought to test whether a single lateral fluid percussion brain injury impairs cognitive performance in conditioned fear. Brain-injured mice were evaluated for anterograde cognitive deficits, with the hypothesis that acute injury-induced impairments improve over time. Male C57BL/6J mice were brain-injured, trained at 5 or 27 days post-injury, and tested 48 h later for recall of the association between the conditioned stimuli (trained context or cue) and the unconditioned stimulus (foot shock) by quantifying fear-associated freezing behavior. A significant anterograde hippocampal-dependent cognitive deficit was observed at 7 days in brain-injured compared to sham. Cued fear conditioning could not detect amygdala-dependent cognitive deficits after injury and stereological estimation of amygdala neuron number corroborated this finding. The absence of injury-related freezing in a novel context substantiated injury-induced hippocampal-dependent cognitive dysfunction, rather than generalized fear. Variations in the training and testing paradigms demonstrated a cognitive deficit in consolidation, rather than acquisition or recall. By 1-month post-injury, cognitive function recovered in brain-injured mice. Hence, the acute injury-induced cognitive impairment may persist while transient pathophysiological sequelae are underway, and improve as global dysfunction subsides.

Original languageEnglish (US)
Pages (from-to)347-357
Number of pages11
JournalBehavioural Brain Research
Volume177
Issue number2
DOIs
StatePublished - Feb 27 2007
Externally publishedYes

Fingerprint

Percussion
Brain Injuries
Fear
Wounds and Injuries
Cues
Amygdala
Brain
Freezing
Foot
Shock
Cognitive Dysfunction
Inbred C57BL Mouse
Cognition
Hippocampus
Neurons

Keywords

  • Amygdala
  • Disector
  • Fractionator
  • Head Injury
  • Hippocampus
  • Mouse
  • Stereology
  • TBI

ASJC Scopus subject areas

  • Behavioral Neuroscience

Cite this

Acute cognitive impairment after lateral fluid percussion brain injury recovers by 1 month : Evaluation by conditioned fear response. / Lifshitz, Jonathan; Witgen, Brent M.; Grady, M. Sean.

In: Behavioural Brain Research, Vol. 177, No. 2, 27.02.2007, p. 347-357.

Research output: Contribution to journalArticle

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