bioRxiv. 2023 Apr 11. pii: 2023.04.11.536335. [Epub ahead of print]
Sensory signals are processed by the cerebellum to coordinate movements. Numerous cerebellar functions are thought to require the maintenance of a sensory representation that extends beyond the input signal. Granule cells receive sensory input, but they do not prolong the signal and are thus unlikely to maintain a sensory representation for much longer than the inputs themselves. Unipolar brush cells (UBCs) are excitatory interneurons that project to granule cells and transform sensory input into prolonged increases or decreases in firing, depending on their ON or OFF UBC subtype. Further extension and diversification of the input signal could be produced by UBCs that project to one another, but whether this circuitry exists is unclear. Here we test whether UBCs innervate one another and explore how these small networks of UBCs could transform spiking patterns. We characterized two transgenic mouse lines electrophysiologically and immunohistochemically to confirm that they label ON and OFF UBC subtypes and crossed them together, revealing that ON and OFF UBCs innervate one another. A Brainbow reporter was used to label UBCs of the same ON or OFF subtype with different fluorescent proteins, which showed that UBCs innervate their own subtypes as well. Computational models predict that these feed-forward networks of UBCs extend the length of bursts or pauses and introduce delaysâ€"transformations that may be necessary for cerebellar functions from modulation of eye movements to adaptive learning across time scales.SIGNIFICANCE STATEMENT: The cerebellum is essential for the accurate performance of behaviors ranging in complexity from stabilizing an image on the retina to playing a piano or performing a gymnastics routine. Cerebellar dysfunction disrupts the ability to produce smooth movements and leads to a disorder called ataxia. Damage to the vestibular cerebellum occurs in various disorders including medulloblastoma and leads to nystagmus, involuntary movements of the eyes that prevent normal vision. Treating disorders of motor control such as nystagmus, requires a better understanding of how representations of movements are maintained in the firing patterns of neurons in the cerebellar circuit. Here we use transgenic mice to label a type of neuron called the unipolar brush cell and revealed that these cells innervate one another and are likely to increase the length and diversity of spiking patterns in the cerebellum. These transformations may be necessary for numerous functions from controlling eye movements to learning new behaviors.