Specific stimulation of PV+ neurons at early stage ameliorates prefrontal ischemia-induced spatial working memory impairment

Autor: Chao He, Chao Li, Youhong Xie, Jun Hu, Lin Chen, Jiankun Mu, Guang-yan Wu, Jian-ning Ye
Rok vydání: 2021
Předmět:
Zdroj: Behavioural Brain Research. 414:113511
ISSN: 0166-4328
DOI: 10.1016/j.bbr.2021.113511
Popis: Prefrontal ischemia can cause impairments in learning and memory, executive functions and cognitive flexibility. However, the related cellular mechanisms at the early stage are still elusive. The present study used ischemic stroke in medial prefrontal cortex and systemically investigated the electrophysiological changes of the parvalbumin (PV+) interneurons 12 h post ischemia. We found that Ih and the related voltage sags in PV+ interneurons are downregulated post ischemia, which correlates with hyperpolarization of the membrane potentials and increased input resistance in these interneurons. Consistent with the suppression of Ih, postischemic PV+ interneurons exhibited a reduction in excitability and exerted a less inhibitory control over the neighboring pyramidal excitatory neurons. Moreover, we found that specifically chemogenetic activation of PV+ neurons at early stage ameliorated prefrontal ischemia-induced spatial working memory dysfunction in T-maze without effects on the locomotor coordination and balance. In contrast, suppression of PV+ neurons by blockade of Ih leaded to further aggravate the damage of spatial memory. These findings indicate that dysfunctional Ih in the PV+ neuron postischemia induces the imbalance of excitation and inhibition, which might represent a novel mechanism underlying the prefrontal ischemia-induced cognitive impairment.
Databáze: OpenAIRE