Sustained Activity of Hippocampal Parvalbumin-Expressing Interneurons Supports Trace Eyeblink Conditioning in Mice.

Although recent studies have revealed an involvement of hippocampal interneurons in learning the association among time-separated events, its underlying cellular mechanisms remained not fully clarified. Here, we combined multichannel recording and optogenetics to elucidate how the hippocampal parvalbumin-expressing interneurons (PV-INs) support associative learning. To address this issue, we trained the mice (both sexes) to learn hippocampus-dependent trace eyeblink conditioning (tEBC) in which they associated a light flash conditioned stimulus (CS) with a corneal air puff unconditioned stimuli (US) separated by a 250 ms time interval. We found that the hippocampal PV-INs exhibited learning-associated sustained activity at the early stage of tEBC acquisition. Moreover, the PV-IN sustained activity was positively correlated with the occurrence of conditioned eyeblink responses at the early learning stage. Suppression of the PV-IN sustained activity impaired the acquisition of tEBC, whereas the PV-IN activity suppression had no effect on the acquisition of delay eyeblink conditioning, a hippocampus-independent learning task. Learning-associated augmentation in the excitatory pyramidal cell-to-PVIN drive may contribute to the formation of PV-IN sustained activity. Suppression of the PV-IN sustained activity disrupted hippocampal gamma but not theta band oscillation during the CS-US interval period. Gamma frequency (40 Hz) activation of the PV-INs during the CS-US interval period facilitated the acquisition of tEBC. Our current findings highlight the involvement of hippocampal PV-INs in tEBC acquisition and reveal insights into the PV-IN activity kinetics which are of key importance for the hippocampal involvement in associative learning.