Disengagement of Motor Cortex during Long-Term Learning Tracks the Performance Level of Learned Movements.

Not all movements require the motor cortex for execution. Intriguingly, dependence on motor cortex of a given movement is not fixed, but instead can dynamically change over the course of long-term learning. For instance, rodent forelimb movements that initially require motor cortex can become independent of the motor cortex after an extended period of training. However, it remains unclear whether long-term neural changes rendering the motor cortex dispensable are a simple function of the training length. To address this issue, we trained mice (both male and female) to perform two distinct forelimb movements, forward versus downward reaches with a joystick, concomitantly over several weeks, and then compared the involvement of the motor cortex between the two movements. Most mice achieved different levels of motor performance between the two movements after long-term training. Of the two movements, the one that achieved higher trial-to-trial consistency (i.e., consistent-direction movement) was significantly less affected by inactivation of motor cortex than the other (i.e., variable-direction movement). Two-photon calcium imaging of motor cortical neurons revealed that the consistent-direction movement activates fewer neurons, producing weaker and less consistent population activity than the variable-direction movement. Together, the motor cortex was less engaged and less necessary for learned movements that achieved higher levels of consistency. Thus, the long-term reorganization of neural circuits that frees the motor cortex from the learned movement is not a mere function of training length. Rather, this reorganization tracks the level of motor performance that the animal achieves during training.SIGNIFICANCE STATEMENT Long-term training of a movement reshapes motor circuits, disengaging motor cortex potentially for automatized execution of the learned movement. Acquiring new motor skills often involves learning of multiple movements (e.g., forehand and backhand strokes when learning tennis), but different movements do not always improve at the same time nor reach the same level of proficiency. Here we showed that the involvement of motor cortex after long-term training differs between similar yet distinct movements that reached different levels of expertise. Motor cortex was less engaged and less necessary for the more proficient movement. Thus, disengagement of motor cortex is not a simple function of training time, but instead tracks the level of expertise of a learned movement.

Disengagement of motor cortex from movement control during long-term learning.

Motor learning involves reorganization of the primary motor cortex (M1). However, it remains unclear how the involvement of M1 in movement control changes during long-term learning. To address this, we trained mice in a forelimb-based motor task over months and performed optogenetic inactivation and two-photon calcium imaging in M1 during the long-term training. We found that M1 inactivation impaired the forelimb movements in the early and middle stages, but not in the late stage, indicating that the movements that initially required M1 became independent of M1. As previously shown, M1 population activity became more consistent across trials from the early to middle stage while task performance rapidly improved. However, from the middle to late stage, M1 population activity became again variable despite consistent expert behaviors. This later decline in activity consistency suggests dissociation between M1 and movements. These findings suggest that long-term motor learning can disengage M1 from movement control.

History-based action selection bias in posterior parietal cortex.

Making decisions based on choice-outcome history is a crucial, adaptive ability in life. However, the neural circuit mechanisms underlying history-dependent decision-making are poorly understood. In particular, history-related signals have been found in many brain areas during various decision-making tasks, but the causal involvement of these signals in guiding behavior is unclear. Here we addressed this issue utilizing behavioral modeling, two-photon calcium imaging, and optogenetic inactivation in mice. We report that a subset of neurons in the posterior parietal cortex (PPC) closely reflect the choice-outcome history and history-dependent decision biases, and PPC inactivation diminishes the history dependency of choice. Specifically, many PPC neurons show history- and bias-tuning during the inter-trial intervals (ITI), and history dependency of choice is affected by PPC inactivation during ITI and not during trial. These results indicate that PPC is a critical region mediating the subjective use of history in biasing action selection.

Activity regulates functional connectivity from the vomeronasal organ to the accessory olfactory bulb.

The mammalian accessory olfactory system is specialized for the detection of chemicals that identify kin and conspecifics. Vomeronasal sensory neurons (VSNs) residing in the vomeronasal organ project axons to the accessory olfactory bulb (AOB), where they form synapses with principal neurons known as mitral cells. The organization of this projection is quite precise and is believed to be essential for appropriate function of this system. However, how this precise connectivity is established is unknown. We show here that in mice the vomeronasal duct is open at birth, allowing external chemical stimuli access to sensory neurons, and that these sensory neurons are capable of releasing neurotransmitter to downstream neurons as early as the first postnatal day (P). Using major histocompatibility complex class I peptides to activate a selective subset of VSNs during the first few postnatal days of development, we show that increased activity results in exuberant VSN axonal projections and a delay in axonal coalescence into well defined glomeruli in the AOB. Finally, we show that mitral cell dendritic refinement occurs just after the coalescence of presynaptic axons. Such a mechanism may allow the formation of precise connectivity with specific glomeruli that receive input from sensory neurons expressing the same receptor type.

Morphological analysis of activity-reduced adult-born neurons in the mouse olfactory bulb.

Adult-born neurons (ABNs) are added to the olfactory bulb (OB) throughout life in rodents. While many factors have been identified as regulating the survival and integration of ABNs into existing circuitry, the understanding of how these factors affect ABN morphology and connectivity is limited. Here we compare how cell intrinsic [small interfering RNA (siRNA) knock-down of voltage gated sodium channels Na(V)1.1-1.3] and circuit level (naris occlusion) reductions in activity affect ABN morphology during integration into the OB. We found that both manipulations reduce the number of dendritic spines (and thus likely the number of reciprocal synaptic connections) formed with the surrounding circuitry and inhibited dendritic ramification of ABNs. Further, we identified regions of ABN apical dendrites where the largest and most significant decreases occur following siRNA knock-down or naris occlusion. In siRNA knock-down cells, reduction of spines is observed in proximal regions of the apical dendrite. This suggests that distal regions of the dendrite may remain active independent of Na(V)1.1-1.3 channel expression, perhaps facilitated by activation of T-type calcium channels and NMDA receptors. By contrast, circuit level reduction of activity by naris occlusion resulted in a global depression of spine number. Together, these results indicate that ABNs retain the ability to develop their typical overall morphological features regardless of experienced activity, and activity modulates the number and location of formed connections.