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Proc Natl Acad Sci U S A. 2019 Dec 16. pii: 201913227. doi: 10.1073/pnas.1913227117. [Epub ahead of print]

Reactivation of critical period plasticity in adult auditory cortex through chemogenetic silencing of parvalbumin-positive interneurons.

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Montreal Neurological Institute, McGill University, Montreal, QC H3A 2B4, Canada;
Centre for Research on Brain, Language and Music, McGill University, Montreal, QC H3G 2A8, Canada.


Sensory experience during early developmental critical periods (CPs) has profound and long-lasting effects on cortical sensory processing perduring well into adulthood. Although recent evidence has shown that reducing cortical inhibition during adulthood reinstates CP plasticity, the precise cellular mechanisms are not well understood. Here, we show that chemogenetic inactivation of parvalbumin-positive (PV+) interneurons is sufficient to reinstate CP plasticity in the adult auditory cortex. Bidirectional manipulation of PV+ cell activity affected neuronal spectral and sound intensity selectivity and, in the case of PV+ interneuron inactivation, was mirrored by anatomical changes in PV and associated perineuronal net expression. These findings underscore the importance of sustained PV-mediated inhibitory neurotransmission throughout life and highlight the potential of chemogenetic approaches for harnessing cortical plasticity with the ultimate goal of aiding recovery from brain injury or disease.


GABA; auditory cortex; parvalbumin; perineuronal nets; plasticity

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