Synaptic and spiking activity of cerebellar neurons during learning and swimming in larval zebrafishPublic Deposited
The cerebellum contributes to movement initiation, execution, and adaptation. Primary cerebellar neurons receive synaptic inputs related to sensory stimuli and motor commands, leading to modulation of their firing. Furthermore, synaptic input differs substantially between cerebellum-dependent behaviors. I have made voltage- and current-clamp recordings from Purkinje and eurydendroid neurons in the larval zebrafish cerebellum while simultaneously recording fictive swimming from the ventral root in the tail to describe the synaptic inputs and spiking activity of these cells while the fish was at rest, during visual sensory stimulation, spontaneous swimming, and sensory-evoked reflexive swimming. For Purkinje cells, I have tested how plasticity manifests in individual neurons during associative motor learning by following synaptic activity and spiking from when the fish is naÃ¯ve to when it reliably performs learned swimming. I discovered differences in Purkinje cell spiking during learned swimming that reflected different forms of plasticity, were partially predicted by basal synaptic properties, and related to the position of the cell. Using optogenetics to manipulate Purkinje cell activity, I found that Purkinje simple spikes can play a transient, instructive role during learning. For eurydendroid neurons, I found that inhibition from Purkinje complex spikes is similar to that from simple spikes, and that 2-7 Purkinje cells converge onto each cell. Spiking is differentially modulated during cerebellar behaviors. Acute excitation makes spiking more likely during visual stimuli. During swimming, spiking is anticorrelated with inhibitory drive, which is rhythmic during volitional but not reflexive swimming. Overall, my experiments demonstrate differential responses of cerebellar neurons to movements, diversity among neurons in the types of synaptic drive they receive, and multiple forms of plasticity that support different aspects of cerebellar learning. Many of my findings match those from experiments on the cerebellum of mammals, revealing properties of this circuit that are likely conserved across all vertebrates.