Cell responses to synaptic inputs are regulated by K+ ion channels that stabilize a cell membrane. Cortical inputs directly come into distal dendrites of hippocampal CA3 pyramidal neurons (PNs), at which Kv1.2 (one of low-voltage activated K channels) is high expressed. We found that reducing Kv1.2 to a half in CA3-PNs facilitates long-term potentiation (LTP) specifically at direct cortical synapses. In the present study, we investigated the behavioral consequences of the Kv1.2 mutation. 

Information is represented by a subset of principal neurons, called neuronal ensemble. Input patterns in the CA3 are represented by a small number of principal neurons (sparse coding) to prevent overlap of input patterns. This sparse coding depends on pre-processed inputs from dentate gyrus (DG), an upstream of CA3 area, which decorrelates ensembles activated by two similar but slightly distinct contexts (pattern separation). The DG inputs instruct for LTP at direct cortical synapse onto CA3-PNs. In Kv1.2 mutant animals, this rule is violated. 

We found that Kv1.2 mutant animals are normal in tasks requiring pattern completion or pattern separation depending on one-trial learning. These animals were specifically impaired in gradual decorrelation of neuronal ensembles representing two similar contexts over the training days. Our study highlights the role of sparse LTP at PP-CA3 synapse probably supervised by mossy fiber inputs in gradual decorrelation of CA3 ensembles.