4.8 Article

Mature parvalbumin interneuron function in prefrontal cortex requires activity during a postnatal sensitive period

Journal

ELIFE
Volume 11, Issue -, Pages -

Publisher

eLIFE SCIENCES PUBL LTD
DOI: 10.7554/eLife.80324

Keywords

prefrontal cortex; development; parvalbumin; interneurons; gamma oscillations; cognitive flexibility

Categories

Funding

  1. Brain and Behavior Research Foundation [26089, 27384]
  2. National Institute of Mental Health [K01MH107760, R01MH128277, F31 MH119691, K08MH109735, R21 MH121334, MH117454]

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In their study, Hubel and Wiesel identified sensitive periods where experience can have long-lasting effects on adult visual cortical functioning and behavior through changes in neuronal activity. They investigated whether similar sensitive periods exist for non-sensory cortices and found that inhibition of prefrontal parvalbumin (PV)-expressing interneurons during the juvenile and adolescent period leads to persistent impairments in adult prefrontal circuit connectivity, in vivo network function, and behavioral flexibility, which can be reversed by targeted activation of PV interneurons in adulthood.
In their seminal findings, Hubel and Wiesel identified sensitive periods in which experience can exert lasting effects on adult visual cortical functioning and behavior via transient changes in neuronal activity during development. Whether comparable sensitive periods exist for non-sensory cortices, such as the prefrontal cortex, in which alterations in activity determine adult circuit function and behavior is still an active area of research. Here, using mice we demonstrate that inhibition of prefrontal parvalbumin (PV)-expressing interneurons during the juvenile and adolescent period, results in persistent impairments in adult prefrontal circuit connectivity, in vivo network function, and behavioral flexibility that can be reversed by targeted activation of PV interneurons in adulthood. In contrast, reversible suppression of PV interneuron activity in adulthood produces no lasting effects. These findings identify an activity-dependent sensitive period for prefrontal circuit maturation and highlight how abnormal PV interneuron activity during development alters adult prefrontal circuit function and cognitive behavior.

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