Kv1.2 contributes to pattern separation by regulating the hippocampal CA3 neuronal ensemble size

Abstract

Kv1.2 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.

A pathogenic missense mutation in kainate receptors elevates dendritic excitability and synaptic integration through dysregulation of SK channels

“…The induction of Hebbian synaptic potentiation of distal synapses is affected by active conductances in the dendritic compartment [38][39][40] . As there appeared to be a change in the dendritic properties of CA3 neurons in A657T mice, we next tested the prediction that the threshold for NMDA-dependent LTP of AC synapses is reduced by inducing plasticity with a sub-maximal train of stimuli.…”

“…When the peaks were not clearly distinguishable, mAHP and sAHP were measured at 50 -100 ms (mAHP) and 500 -1000 ms (sAHP) after the depolarization. In voltage clamp recordings, I mAHP and I sAHP were evoked by depolarizing the cells from -60 mV to +60 mV with square pulses (40,80,160, and 320 ms) and peaks measured typically at several tens of ms for I mAHP and several hundreds of ms for I sAHP after the depolarization. When the peak currents were not clearly delineated the, I mAHP and I sAHP were measured 20 -100 ms (I mAHP ) and 150 -1150 ms (I sAHP ) after the depolarization.…”