Removing the brake on the brain’s ability to learn

Imagine when you are learning to play a long string of notes on a piano or to make a golf swing at a driving range, what is changing in your brain that allows you to learn those movements? The motor cortex in the brain has been shown to play an active role in the learning of new motor skills, and here we describe a specific type of inhibitory neuron in the motor cortex that is responsible for gating the changes required for the learning of new skilled movements.

HFSP Long-Term Fellow Simon Chen and HFSP Young Investigator Grant holder Takaki Komiyama
authored on Tue, 14 July 2015

Mammals exhibit a great degree of flexibility in motor control. With repetitive training and practice, we can achieve highly skilled and reproducible movements. The motor cortex plays a critical role in motor learning. However, little is known about how the changes of the motor cortex are regulated during the acquisition of a new movement. In order to study this question, we developed a motor learning behavior task for head-fixed mice, which allows us to image the motor cortex through a transcranial window while the animal undergoes training. Mice were trained to press a lever using their left forelimb in order to get a water reward. Over two weeks of training, the movements on individual trials became more similar to each other, suggesting that mice gradually formed a stereotyped and reproducible movement. 

Motor skill learning has been shown to induce reorganizations of dendritic spines, principle sites of excitatory synapses, in the motor cortex, and the survival of learning-induced new spines is thought to be a basis for long-lasting motor memories. By combining in vivo transcranial two-photon imaging with the head-fixed lever press task, we found that spine reorganization of excitatory neurons in the motor cortex occurs only in the distal branches of the apical dendrites in layer 1 (L1) but not in the perisomatic dendrites. How is the compartment specificity of excitatory synaptic changes regulated? As a potential mechanism, we focused on the local inhibitory circuits since they are important in regulating excitatory synaptic plasticity. We examined somatostatin-expressing and parvalbumin-expressing inhibitory neurons (SOM-INs and PV-INs) because SOM-INs mainly inhibit distal dendrites of excitatory neurons while PV-INs mainly inhibit persiomatic regions. Imaging the same axonal branches of SOM-INs or PV-INs during learning revealed a decrease in the number of synapses made by SOM-INs immediately after the training began, whereas PV-INs exhibited a gradual increase in the number of synapses during training. 

The observation of spine reorganization in distal dendrites coupled with the rapid loss of SOM-IN synapses during the initial phase of motor learning led us to hypothesize that the resulting reduction in dendritic inhibition may create a condition that allows learning-related changes in dendritic spines to occur. To test this hypothesis, we utilized the optogenetic tools, channelrhodopsin or halorhodopsin, to either enhance or suppress SOM-IN activity during learning, respectively. We found that both manipulations affected the stability of spines on excitatory neurons and impaired motor learning. Therefore, the level of SOM-IN inhibition during learning is critical for spine stability, in which too much or too little SOM inhibition is detrimental to spine reorganization and motor learning. Together, our results identify a specific neuron type that controls the circuit plasticity important for motor learning. Future studies will determine whether similar mechanisms are involved in other forms of learning and whether they are compromised in learning disorders.

Reference

Subtype-specific plasticity of inhibitory circuits in motor cortex during motor learning. Simon X Chen, An Na Kim, Andrew J Peters & Takaki Komiyama. Nature Neuroscience (2015) doi:10.1038/nn.4049.

Pubmed link