Cell-type-specific responses to associative learning in the primary motor cortex

Abstract

The primary motor cortex (M1) is known to be a critical site for movement initiation and motor learning. Surprisingly, it has also been shown to possess reward-related activity, presumably to facilitate reward-based learning of new movements. However, whether reward-related signals are represented among different cell types in M1, and whether their response properties change after cue-reward conditioning remains unclear. Here, we performed longitudinal in vivo two-photon Ca2+ imaging to monitor the activity of different neuronal cell types in M1 while mice engaged in a classical conditioning task. Our results demonstrate that most of the major neuronal cell types in M1 showed robust but differential responses to both the conditioned cue stimulus (CS) and reward, and their response properties undergo cell-type specific modifications after associative learning. PV-INs' responses became more reliable to the CS, while VIP-INs' responses became more reliable to reward. PNs only showed robust responses to novel reward, and they habituated to it after associative learning. Lastly, SOM-INs' responses emerged and became more reliable to both the CS and reward after conditioning. These observations suggest that cue- and reward-related signals are preferentially represented among different neuronal cell types in M1, and the distinct modifications they undergo during associative learning could be essential in triggering different aspects of local circuit reorganization in M1 during reward-based motor skill learning.

Continuous estimation of reaching space in superficial layers of the motor cortex

“…The majority of studies of motor control typically focus on a range of behavioral phases strictly related to movement, such as instruction, preparation and execution. However, neurons in motor and premotor cortices have been implicated in higher order phenomena that extend beyond movement, such as reward processing, behavioral outcome or memory traces 32,33,34 . Whether neurons in the MAC encode these kinds of signals and how spatial information is integrated with them, is less clear.…”

Inhibitory Plasticity Enhances Sequence Storage Capacity and Retrieval Robustness

“…How sequences are learned and retrieved has been studied by theorists for decades. However, few studies have addressed the roles of inhibitory plasticity apart from maintaining E-I balance, in spite of the fact that multiple forms of inhibitory plasticity have been found experimentally [4, 9, 14, 22, 23, 26, 32, 49, 53, 57], and suggested to be critical in sequence learning [1, 4, 22, 29, 49]. Why do various forms of inhibitory plasticity exist, and how do they affect sequence learning?…”

“…All models described so far either do not respect Dale’s law, or involve only recurrent excitatory (E→ E) plasticity. However, emerging evidence suggests that inhibitory neurons are involved in different forms of synaptic plasticity [4, 9, 14, 22, 23, 26, 32, 49, 53, 57], and may play important roles in sequence learning [1, 4, 22, 29, 49], in addition to maintaining E-I balance. For example, in spatial navigation tasks, up- and down-regulating LTP at excitatory synapses onto hippocampal CA1 somatostasin-expressing interneurons (SOM-INs) bidirectionally regulate spatial memory [4].…”

Stimulus-reward contingencies drive long-lasting alterations in neocortical somatostatin inhibition during learning

“…Experimental evidence suggests that across sensory neocortex, SST neurons can respond to behavioral variables such as reward and novelty (Lee et al, 2022; Ren et al, 2022). Our data indicate that behaviorally-relevant stimuli not only dynamically alter SST responses but also initiate long-term depression at SST outputs.…”