Kv1.2 contributes to pattern separation by regulating the hippocampal CA3 neuronal ensemble size
AbstractKv1.2 expression in rodent CA3 pyramidal cells (CA3-PC) is polarized to distal apical dendrites, and regulate the synaptic responses to perforant pathway (PP) inputs. Accordingly, Kv1.2 haploinsufficiency (Kcna2+/−) in CA3-PCs, but not Kv1.1 (Kcna1+/−), lowered the threshold for long-term potentiation at PP-CA3 synapses. The Kcna2+/− mice, but not Kcna1+/−, displayed impairments in contextual fear discrimination task. The size and overlap of CA3 ensembles activated by the first visits to slightly different contexts were not different between wildtype and Kcna2+/− mice, but these ensemble parameters diverged over training days between genotypes, suggesting abnormal plastic changes in the CA3 network of Kcna2+/− mice. Eventually, the Kcna2+/− mice exhibited larger ensemble size and overlap upon retrieval of two contexts, compared to wildtype or Kcna1+/− mice. These results suggest that Kv1.2 subunits prevent promiscuous plastic changes at PP-CA3 synapses, and contribute to sparse representation of memories and pattern separation in the CA3 network.