Carbamazepine reduces sharp wave-ripple complexes and exerts synapse-specific inhibition of neurotransmission in ex vivo hippocampal slices

Timothy A. Simeone, Segewkal H. Heruye, Joseph A. Kostansek, Mary Y. Yeh, Stephanie A. Matthews, Kaeli K. Samson, Kristina A. Simeone

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Higher therapeutic concentrations of the antiseizure medication carbamazepine (CBZ) are associated with cognitive side effects. Hippocampal sharp wave-ripple complexes (SPW-Rs) are proposed to participate in memory consolidation during periods of quiet and slow-wave sleep. SPW-Rs are generated in the CA3 region and are regulated by multiple synaptic inputs. Here, we used a multi-electrode array to determine the effects of CBZ on SPW-Rs and synaptic transmission at multiple hippocampal synapses. Our results demonstrate that CBZ reduced SPW-Rs at therapeutically relevant concentrations (IC50 = 37 µM) and altered the core characteristics of ripples, important for information processing and consolidation. Moreover, CBZ inhibited neurotransmission in a synapse-specific manner. CBZ inhibition was most potent at the medial-perforant-path-to-CA3 and mossy-fiber-to-CA3 synapses (IC50s ~ 30 and 60 µM, respectively) and least potent at medialperforant- path-to-dentate granule cell synapses (IC50 ~ 120 µM). These results suggest that the synapse-specific CBZ inhibition of neurotransmission reduces SPW-Rs and that the CBZ inhibition of SPW-Rs may underlie the cognitive impairments observed with therapeutic doses of CBZ.

Original languageEnglish (US)
Article number787
JournalBrain Sciences
Volume11
Issue number6
DOIs
StatePublished - Jun 2021

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

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