Bidirectional optogenetically-induced plasticity of evoked responses in the rat medial prefrontal cortex can impair or enhance cognitive set-shifting

Sarah E. Bulin, Kelly M. Hohl, Denisse Paredes, Jeri D. Silva, David A. Morilak

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Chronic stress compromises cognition, including executive function mediated in the medial prefrontal cortex (mPFC). To investigate mechanisms underlying these processes, we use chronic unpredictable stress (CUS), which reduces activity in the mPFC and impairs cognitive set-shifting, a measure of cognitive flexibility in laboratory rats. It has been shown that CUS attenuates the local electrical field potential response evoked in the mPFC by stimulation of the ascending excitatory afferent from the mediodorsal thalamus (MDT). Thus, in this study, to investigate the role that such changes in afferent-evoked responsivity of the mPFC might play in the cognitive deficits induced by CUS, we used optogenetics to directly induce plastic changes in the thalamic-mPFC afferent pathway. Glutamatergic neurons in the MDT were virally-induced to express the ChETA variant of channelrhodopsin. Then, to first validate the optogenetic induction of plasticity, long-term depression (LTD) or long-term potentiation (LTP) were induced by laser stimulation of ChETA-expressing terminals in the mPFC of anesthetized rats. In subsequent experiments, induction of opto-LTD in awake animals produced set-shifting deficits similar to those induced by CUS. By contrast, inducing opto-LTP in rats that had received prior CUS treatment corrected the stress-induced deficit in set-shifting. These results suggest that stress-induced plasticity in the thalamic-mPFC pathway is sufficient to produce stress-induced cognitive deficits, and may represent a novel target for effective therapeutic intervention to correct cognitive impairment in stress-related psychiatric disorders.

Original languageEnglish (US)
Article numberENEURO.0363-19.2019
JournaleNeuro
Volume7
Issue number1
DOIs
StatePublished - Jan 1 2020

Keywords

  • Chronic stress
  • Cognitive flexibility
  • Medial prefrontal cortex
  • Neuroplasticity
  • Optogenetics
  • Set-shifting

ASJC Scopus subject areas

  • Neuroscience(all)

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