Gene Deficiency of δ Subunit-Containing GABAA Receptor in mPFC Lead Learning and Memory Impairment in Mice

Authors:
Publisher website
Google Scholar
Abstract
Maintaining GABAergic inhibition within physiological limits in the medial prefrontal cortex (mPFC) is critical for working memory. While synaptic GABAAR typically mediate the primary component of mPFC inhibition, the role of extrasynaptic δ-GABAAR in working memory remains unclear. To investigate this, we used fiber photometry to examine the effects of δ-GABAAR in freely moving mice. Our results indicate that the loss of δ-GABAAR expression leads to learning and memory impairment. Specifically, activation of δ-GABAAR impaired learning and memory in WT mice but enhanced learning and memory in δ+/− knockout mice. Furthermore, δ-GABAAR activation increased calcium activity in the mPFC pyramidal neurons, an effect not observed in δ-Cas9-sgRNA virus-infected mice. Collectively, these findings suggest that δ-GABAAR deficiency impairs learning and memory by modulating the excitability of pyramidal neurons in the mPFC. These results delineate the functional contribution of δ-GABAAR to learning and memory, suggesting their role extends beyond the mere maintenance of information.
Funding Information
  • National Natural Science Foundation of China (12104273, 82101608)
  • Natural Science Foundation of Shandong Province (ZR2021QH309)
  • College Youth Innovation Team of Shandong Province (2022KJ255)
  • STI2030-Major Projects (2021ZD0202900)
  • Major Instrument R&D of the National Natural Science Foundation of China (62027812)

This publication has 39 references indexed in Scilit: