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Mechanisms and plasticity of chemogenically induced interneuronal suppression of principal cells.

ABSTRACT: How do firing patterns in a cortical circuit change when inhibitory neurons are excited? We virally expressed an excitatory designer receptor exclusively activated by a designer drug (Gq-DREADD) in all inhibitory interneuron types of the CA1 region of the hippocampus in the rat. While clozapine N-oxide (CNO) activation of interneurons suppressed firing of pyramidal cells, unexpectedly the majority of interneurons also decreased their activity. CNO-induced inhibition decreased over repeated sessions, which we attribute to long-term synaptic plasticity between interneurons and pyramidal cells. Individual interneurons did not display sustained firing but instead transiently enhanced their activity, interleaved with suppression of others. The power of the local fields in the theta band was unaffected, while power at higher frequencies was attenuated, likely reflecting reduced pyramidal neuron spiking. The incidence of sharp wave ripples decreased but the surviving ripples were associated with stronger population firing compared with the control condition. These findings demonstrate that DREADD activation of interneurons brings about both short-term and long-term circuit reorganization, which should be taken into account in the interpretation of chemogenic effects on behavior.

SUBMITTER: Rogers S

PROVIDER: S-EPMC7812748 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Mechanisms and plasticity of chemogenically induced interneuronal suppression of principal cells.

Rogers Stephanie S Rozman Peter A PA Valero Manuel M Doyle Werner K WK Buzsáki György G

Proceedings of the National Academy of Sciences of the United States of America 20201221 2

How do firing patterns in a cortical circuit change when inhibitory neurons are excited? We virally expressed an excitatory designer receptor exclusively activated by a designer drug (Gq-DREADD) in all inhibitory interneuron types of the CA1 region of the hippocampus in the rat. While clozapine N-oxide (CNO) activation of interneurons suppressed firing of pyramidal cells, unexpectedly the majority of interneurons also decreased their activity. CNO-induced inhibition decreased over repeated sessi ...[more]

PMID: 33372130

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Mechanisms and plasticity of chemogenically induced interneuronal suppression of principal cells.

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Mechanisms and plasticity of chemogenically induced interneuronal suppression of principal cells.

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