In Vivo Dendritic Dynamics of Somatostatin-Expressing Interneurons (SST-INs) in the Primary Motor Cortex (M1) During Motor Learning

Abstract

The primary motor cortex (M1) is critical for motor learning. Within M1, excitatory pyramidal neurons (PyrNs) undergo network re-organizations, forming task-specific ensembles. This process was recently discovered to be modulated by a functionally distinct ensemble of somatostatin-expressing inhibitory neurons (SST-INs) in M1 that predominantly express neuronal PAS domain 4 (NPAS4) upon motor learning. NPAS4+ SST-INs reduced inhibition onto postsynaptic PyrNs, facilitating circuit reorganization, and thus, motor learning. NPAS4+SST-IN ensemble hints at learning-associated input integration in SST-INs, however, the underpinning of this process remains unclear. To investigate this, I employ in vivo two photon Ca²⁺ imaging in awake mice to chronically monitor dendritic and synaptic activity of SST-INs throughout training for head-restrained bi-directional disk task, followed by identification of NPAS4+ SST-IN ensemble in M1. Building upon finding of branch-specific Ca²⁺ spikes on layer 5 PyrNs' apical dendrites in M1during motor learning, which induces potentiation of learning-related spines, I hypothesize that motor learning-induced dendritic Ca²⁺ activity will trigger and maintain experience-dependent synaptic plasticity in dendrites of NPAS4+ SST-INs. We observed two distinct SST-IN populations during motor training: neurons showing increased ('positive') or decreased ('negative') dendritic activity. Task-specific NPAS4+ SST-INs displayed a nuanced pattern of synaptic integration. In the early training phase, these neurons exhibited broader, non-specific synaptic engagement, characterized by higher spine-dendrite co-activity. As training progressed, we observed a selective refinement of synaptic connections, suggesting an active mechanism of circuit optimization. Overall, this research elucidates dendritic and synaptic plasticity of SST-INs during motor learning, offering insights into neural plasticity and potential therapeutic strategies for neurological injury rehabilitation.