Molecular layer interneurons in the cerebellum encode for valence in associative learning

Abstract

The cerebellum plays a crucial role in sensorimotor and associative learning. However, the contribution of molecular layer interneurons (MLIs) to these processes is not well understood. We used two-photon microscopy to study the role of ensembles of cerebellar MLIs in a go-no go task where mice obtain a sugar water reward if they lick a spout in the presence of the rewarded odorant and avoid a timeout when they refrain from licking for the unrewarded odorant. In naive animals the MLI responses did not differ between the odorants. With learning, the rewarded odorant elicited a large increase in MLI calcium responses, and the identity of the odorant could be decoded from the differential response. Importantly, MLIs switched odorant responses when the valence of the stimuli was reversed. Finally, mice took a longer time to refrain from licking in the presence of the unrewarded odorant and had difficulty becoming proficient when MLIs were inhibited by chemogenetic intervention. Our findings support a role for MLIs in learning valence in the cerebellum.

Multidimensional population activity in an electrically coupled inhibitory circuit in the cerebellar cortex

“…The highly correlated pairwise activity, heterogeneity in response properties, and electrical coupling found in GoCs have also been reported in other inhibitory interneurons ( Gaffield and Christie, 2017 ; Khan et al., 2018 ; Pinto and Dan, 2015 ), raising the possibility that they could have similarly organized population dynamics. Recent recordings from other circuits show that task-relevant information is also available in local inhibitory networks ( Ma et al., 2020 ; Najafi et al., 2020 ). Moreover, our biologically detailed model of the GoC circuit predicts that electrical coupling plays a key role in supporting both common and differential modes.…”

“…By contrast, much less is known about the functional properties of interneurons at the population level as their low density has made it difficult to measure population activity with conventional methods. However, recent advances in microscopy and electrophysiological probes have opened up the possibility of studying the properties of local inhibitory circuits ( Geiller et al., 2020 ; Khan et al., 2018 ; Ma et al., 2020 ; Najafi et al., 2020 ).…”

Mid-lateral cerebellar complex spikes encode multiple independent reward-related signals during reinforcement learning

“…The SS synapse, affected by the CS in motor learning, is not the only modifiable synapse in the cerebellum 39 . For example, the calcium responses of molecular layer interneurons become selective for the rewarded odorant as mice learn which of a pair of odorants is associated with a reward, and which with a punishment (a brief timeout) and an optogenetic inactivation of these cells slows the learning process 40 .…”

Social memory deficit gated by dysregulation of the cerebellar vermis

“…1 & 2, but compromises location-or sequencebased memory via the cerebellum-hippocampus connectivity 23,77 . Moreover, the cerebellum participates in decision-making and consolidation of reward-related go/no-go memory tasks [78][79][80] . As social interactions are rewarding 81 , the cerebellum may promote SRM through its connections to the reward pathway 65 , which significantly overlap with the social brain network [1][2][3] .…”