Seizures initiate in zones of relative hyperexcitation in a zebrafish epilepsy model.

Seizures are thought to arise from an imbalance of excitatory and inhibitory neuronal activity. While most classical studies suggest excessive excitatory neural activity plays a generative role, some recent findings challenge this view and instead argue that excessive activity in inhibitory neurons initiates seizures. We investigated this question of imbalance in a zebrafish seizure model with two-photon imaging of excitatory and inhibitory neuronal activity throughout the brain using a nuclear-localized calcium sensor. We found that seizures consistently initiated in circumscribed zones of the midbrain before propagating to other brain regions. Excitatory neurons were both more prevalent and more likely to be recruited than inhibitory neurons in initiation as compared with propagation zones. These findings support a mechanistic picture whereby seizures initiate in a region of hyperexcitation, then propagate more broadly once inhibitory restraint in the surround is overcome.

Population-scale organization of cerebellar granule neuron signaling during a visuomotor behavior.

Granule cells at the input layer of the cerebellum comprise over half the neurons in the human brain and are thought to be critical for learning. However, little is known about granule neuron signaling at the population scale during behavior. We used calcium imaging in awake zebrafish during optokinetic behavior to record transgenically identified granule neurons throughout a cerebellar population. A significant fraction of the population was responsive at any given time. In contrast to core precerebellar populations, granule neuron responses were relatively heterogeneous, with variation in the degree of rectification and the balance of positive versus negative changes in activity. Functional correlations were strongest for nearby cells, with weak spatial gradients in the degree of rectification and the average sign of response. These data open a new window upon cerebellar function and suggest granule layer signals represent elementary building blocks under-represented in core sensorimotor pathways, thereby enabling the construction of novel patterns of activity for learning.