Sex-specific regulation of inhibition and network activity by local aromatase in the mouse hippocampus

Cognitive function relies on a balanced interplay between excitatory and inhibitory neurons (INs), but the impact of estradiol on IN function is not fully understood. Here, we characterize the regulation of hippocampal INs by aromatase, the enzyme responsible for estradiol synthesis, using a combination of molecular, genetic, functional and behavioral tools. The results show that CA1 parvalbumin-expressing INs (PV-INs) contribute to brain estradiol synthesis. Brain aromatase regulates synaptic inhibition through a mechanism that involves modification of perineuronal nets enwrapping PV-INs. In the female brain, aromatase modulates PV-INs activity, the dynamics of network oscillations and hippocampal-dependent memory. Aromatase regulation of PV-INs and inhibitory synapses is determined by the gonads and independent of sex chromosomes. These results suggest PV-INs are mediators of estrogenic regulation of behaviorally-relevant activity. Using a combination of molecular, genetic, functional and behavioural tools, this study describes the impact of brain synthesized estrogen in inhibitory neuronal function, network oscillations and hippocampal dependent memory.

• Publication year

  2022

• Venue

  Nature Communications

• Publication date

  2022-07-07

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1038/s41467-022-31635-3PMID 35798748PMCID 9262915
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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