Hippocampal Interneurons are Required for Trace Eyeblink Conditioning in Mice

While the hippocampus has been implicated in supporting the association among time-separated events,the underlying cellular mechanisms have not been fully clarified.Here,we combined in vivo multi-channel recording and optogenetics to investigate the activity of hippocampal interneurons in freely-moving mice performing a trace eyeblink conditioning(tEBC)task.We found that the hippocampal interneurons exhibited conditioned stimulus(CS)-evoked sustained activity,which predicted the performance of conditioned eyeblink responses(CRs)in the early acquisition of the tEBC.Consistent with this,greater proportions of hippocampal pyramidal cells showed CS-evoked decreased activity in the early acquisition of the tEBC.Moreover,optogenetic suppression of the sustained activity in hippocampal interneurons severely impaired acquisition of the tEBC.In contrast,suppression of the sustained activity of hippocampal interneurons had no effect on the performance of well-learned CRs.Our findings highlight the role of hippocampal interneurons in the tEBC,and point to a potential cellular mechanism subserving associative learning.

Ventromedial Thalamus-Projecting DCN Neurons Modulate Associative Sensorimotor Responses in Mice

The deep cerebellar nuclei(DCN)integrate various inputs to the cerebellum and form the final cerebellar outputs critical for associative sensorimotor learning.However,the functional relevance of distinct neuronal subpopulations within the DCN remains poorly understood.Here,we examined a subpopulation of mouse DCN neurons whose axons specifically project to the ventromedial(Vm)thalamus(DCNVm neurons),and found that these neurons represent a specific subset of DCN units whose activity varies with trace eyeblink conditioning(tEBC),a classical associative sensorimotor learning task.Upon conditioning,the activity of DCNVm neurons signaled the performance of conditioned eyeblink responses(CRs).Optogenetic activation and inhibition of the DCNVm neurons in well-trained mice amplified and diminished the CRs,respectively.Chemogenetic manipulation of the DCNVm neurons had no effects on non-associative motor coordination.Furthermore,optogenetic activation of the DCNVm neurons caused rapid elevated firing activity in the cingulate cortex,a brain area critical for bridging the time gap between sensory stimuli and motor execution during tEBC.Together,our data highlights DCNVm neurons’function and delineates their kinematic parameters that modulate the strength of associative sensorimotor responses.