Layer 5 Intratelencephalic Neurons in the Motor Cortex Stably Encode Skilled Movement

Abstract

The primary motor cortex (M1) and the dorsal striatum play a critical role in motor learning and the retention of learned behaviors. Motor representations of corticostriatal ensembles emerge during motor learning. In the coordinated reorganization of M1 and the dorsal striatum for motor learning, layer 5a (L5a), which connects M1 to the ipsi- and contra-lateral dorsal striatum, should be a key layer. Although M1 L5a neurons represent movement-related activity in the late stage of learning, it is unclear whether the activity is retained as a memory engram. Here, usingTlx3-Cremale transgenic mice, we conducted two-photon calcium imaging of striatum-projecting L5a intratelencephalic (IT) neurons in forelimb M1 during late sessions of a self-initiated lever-pull task, and in sessions after 6 days of non-training following the late sessions. We found that trained male animals exhibited stable motor performance before and after the non-training days. At the same time, we found that M1 L5a IT neurons strongly represented the well-learned forelimb movement, but not uninstructed orofacial movements. A subset of M1 L5a IT neurons consistently coded the well-learned forelimb movement before and after the non-training days. Inactivation of M1 IT neurons after learning impaired task performance when the lever was made heavier or when the target range of the pull distance was narrowed. These results suggest that a subset of M1 L5a IT neurons continuously represent skilled movement after learning and serve to fine-tune the kinematics of well-learned movement.Significance StatementMotor memory persists even when it is not used for a while. Intratelencephalic neurons in layer 5a (L5a IT neurons) of the primary motor cortex (M1) gradually come to represent skilled forelimb movements during motor learning. However, it remains to be determined whether these changes persist over a long period and how these neurons contribute to skilled movements. Here, we show that a subset of M1 L5a IT neurons retain information for skilled forelimb movements even after non-training days. Furthermore, suppressing the activity of these neurons during skilled forelimb movements impaired behavioral stability and adaptability. Our results suggest the importance of M1 L5a IT neurons for tuning skilled forelimb movements over a long period.

Dopamine-mediated plasticity preserves excitatory connections to direct pathway striatal projection neurons and motor function in a mouse model of Parkinson’s disease

“…Motor cortex provides the main excitatory input to dorsal striatal SPNs and has been shown to be important for both motor learning and execution of movement (Currie et al , 2022; Park et al , 2022, Shinotsuka et al , 2023). We therefore tested whether the preserved mature spines and arbors on dSPNs observed in VGLUT3 KO (and eDREADD+CNO) mice after dopamine depletion reflect the preservation of cortical inputs to dSPNs (Figure 5).…”

Cell-type specialization of layer 5 excitatory neurons in tactile behavior

“…Since the circuit already has PT neurons, which can seemingly do a similar computation more accurately, what could ITs be doing? ITs have been implicated in learning, forming internal models, and preparatory behavior (Salaj et al, 2021), and a recent study showed that learned-but not unlearned-motor behaviors were robustly represented in IT cells of M1 (Shinotsuka et al, 2023). It is possible that ITs’ sharp encoding of preferred object location is partially learned and changes through exposure to behaviorally relevant tasks and stimuli.…”

Layer Va neurons, as major presynaptic partners of corticospinal neurons, play critical roles in skilled movements

“…These neurons also project to CSNs 39 . Contralateral cortex-and striatum-projecting neurons are associated with motor command-like activities, and inactivation of layer Va affects lever task movements [49][50][51] .…”