The cerebellum is crucial for the execution of learned movements. Whether the cerebellum contributes to a given movement depends on the activity of cells in the cerebellar nuclei, which are the sole output of the non- vestibular cerebellum, and Purkinje cells, which form inhibitory synapses onto nuclear cells. Excitatory inputs onto both of these cell types shape their activity, and plasticity at these synapses leads to the emergence of learned movements during cerebellum-dependent associative learning tasks. We have developed a cerebellum-dependent associative learning task for larval zebrafish that allows us to make whole-cell recordings of synaptic activity and spiking from Purkinje neurons and their targets during the acquisition and expression of a learned movement. Preliminary recordings from Purkinje cells during this associative learning task have revealed task-related synaptic activity that evolves across training, eventually leading to activity that approximates the activit observed during the learned movement on subsequent trials. Here, we propose experiments designed to test the following: (1) whether the plasticity observed in Purkinje cell synaptic activity underlies acquisition in this motor learning task; (2) how physiologically distinct Purkine cells contribute to learning and the execution of a learned movement; (3) whether motor learning and synaptic plasticity in this associative learning task are dependent on climbing fiber activity; (4) how the output neurons of the cerebellum change their activity during learning; (5) which premotor areas drive cerebellum-dependent movement; (6) convergence of Purkinje cells onto each output neuron in the teleost cerebellum; and, (7) how Purkinje cell inhibition shapes the activity of output neurons in order to generate movements. These experiments will provide direct evidence for the cerebellar synaptic plasticity mechanisms, which are essential for learned, skillful movements.
During learning, neurons change how they respond to chemical and electrical signals by changing the strength of connections they make with other neurons. We are measuring these changes in the cerebellum - a part of the brain necessary for making skilled movements - in order to understand how motor learning happens.
| Harmon, Thomas C; Magaram, Uri; McLean, David L et al. (2017) Distinct responses of Purkinje neurons and roles of simple spikes during associative motor learning in larval zebrafish. Elife 6: |
