Document Type
Article
Publication Date
8-31-2023
Publication Title
Cell Reports
Abstract
While synaptic plasticity is considered the basis of learning and memory, modifications of the intrinsic excitability of neurons can amplify the output of neuronal circuits and consequently change behavior. However, the mechanisms that underlie learning-induced changes in intrinsic excitability during memory formation are poorly understood. In the cerebellum, we find that silencing molecular layer interneurons completely abolishes fear memory, revealing their critical role in memory consolidation. The fear conditioning paradigm produces a lasting reduction in hyperpolarization-activated cyclic nucleotide-gated (HCN) channels in these interneurons. This change increases intrinsic membrane excitability and enhances the response to synaptic stimuli. HCN loss is driven by a decrease in endocannabinoid levels via altered cGMP signaling. In contrast, an increase in release of cerebellar endocannabinoids during memory consolidation abolishes HCN plasticity. Thus, activity in cerebellar interneurons drives fear memory formation via a learning-specific increase in intrinsic excitability, and this process requires the loss of endocannabinoid-HCN signaling.
First Page
1
Last Page
20
Volume
42
Issue
9
Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-No Derivative Works 4.0 International License.
Recommended Citation
Carzoli, Kathryn Lynn; Kogias, Georgios; Fawcett-Patel, Jessica; and Liu, Si-Qiong J., "Cerebellar interneurons control fear memory consolidation via learning-induced HCN plasticity" (2023). School of Medicine Faculty Publications. 1422.
https://digitalscholar.lsuhsc.edu/som_facpubs/1422