Abstract
Cortical GABAergic interneurons have been shown to fulfil important roles by inhibiting excitatory principal neurons. Recent transcriptomic studies have confirmed seminal discoveries that used anatomical and electrophysiological methods highlighting the existence of multiple different classes of GABAergic interneurons. Although some of these studies have emphasized that inter-regional differences may exist for a given class, the extent of such differences remains unknown. To address this problem, we used single-cell Patch-RNAseq to characterise neuropeptide Y (NPY)-positive GABAergic interneurons in superficial layers of the primary auditory cortex and in distal layers of area CA3 in mice. We found that more than 300 genes are differentially expressed in NPY-positive neurons between these two brain regions. For example, the AMPA receptor auxiliary subunit Shisa9/CKAMP44 and the 5HT2a receptor are significantly higher expressed in auditory NPY-positive neurons. These findings guided us to perform pharmacological experiments that revealed a role for 5HT2a receptors in auditory NPY-positive neurons. Specifically, although the application of 5HT led to a depolarisation of both auditory and CA3 NPY-positive neurons, the 5HT2a receptor antagonist ketanserin only reversed membrane potential changes in auditory NPY-positive neurons. Our study demonstrates the potential of single-cell transcriptomic studies in guiding directed pharmacological experiments.
Significance statement
Using single-cell Patch-RNAseq, we characterised neuropeptide Y (NPY)-positive GABAergic interneurons in superficial layers of the primary auditory cortex and in dendritic layers of CA3. A few hundred genes were found to be differentially expressed in NPY-positive neurons between these two brain regions, including AMPA receptor auxiliary subunit Shisa9/CKAMP44 and the 5HT2a receptor. These findings guided us to perform pharmacological experiments that revealed a role for 5HT2a receptors in superficial auditory NPY-positive neurons.
Footnotes
The authors report no conflict of interest.
The work was supported by the R&KE International (Global engagements) fund, University of Strathclyde, Glasgow, UK to CW, and Swiss National Science Foundation (CRETP3 166815) to CF.
This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license, which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
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