Simple spike patterns and synaptic mechanisms encoding sensory and motor signals in Purkinje cells and the cerebellar nuclei.

Whisker stimulation in awake mice evokes transient suppression of simple spike probability in crus I/II Purkinje cells. Here, we investigated how simple spike suppression arises synaptically, what it encodes, and how it affects cerebellar output. In vitro, monosynaptic parallel fiber (PF)-excitatory postsynaptic currents (EPSCs) facilitated strongly, whereas disynaptic inhibitory postsynaptic currents (IPSCs) remained stable, maximizing relative inhibitory strength at the onset of PF activity.

Simple and complex spike responses of mouse cerebellar Purkinje neurons to regular trains and omissions of somatosensory stimuli.

Cerebellar Purkinje neurons help compute absolute subsecond timing, but how their firing is affected during repetitive sensory stimulation with consistent subsecond intervals remains unaddressed. Here, we investigated how simple and complex spikes of Purkinje cells change during regular application of air puffs (3.3 Hz for ∼4 min) to the whisker pad of awake, head-fixed female mice.

Cerebellar modulation of synaptic input to freezing-related neurons in the periaqueductal gray.

Innate defensive behaviors, such as freezing, are adaptive for avoiding predation. Freezing-related midbrain regions project to the cerebellum, which is known to regulate rapid sensorimotor integration, raising the question of cerebellar contributions to freezing. Here, we find that neurons of the mouse medial (fastigial) cerebellar nuclei (mCbN), which fire spontaneously with wide dynamic ranges, send glutamatergic projections to the ventrolateral periaqueductal gray (vlPAG), which contains diverse cell types.

Effects of FGF14 and Naβ4 deletion on transient and resurgent Na current in cerebellar Purkinje neurons.

Voltage-gated Na channels of Purkinje cells are specialized to maintain high availability during high-frequency repetitive firing. They enter fast-inactivated states relatively slowly and undergo a voltage-dependent open-channel block by an intracellular protein (or proteins) that prevents stable fast inactivation and generates resurgent Na current. These properties depend on the pore-forming α subunits, as well as modulatory subunits within the Na channel complex.

Sensorimotor Integration and Amplification of Reflexive Whisking by Well-Timed Spiking in the Cerebellar Corticonuclear Circuit.

To test how cerebellar crus I/II Purkinje cells and their targets in the lateral cerebellar nuclei (CbN) integrate sensory and motor-related inputs and contribute to reflexive movements, we recorded extracellularly in awake, head-fixed mice during non-contact whisking. Ipsilateral or contralateral air puffs elicited changes in population Purkinje simple spike rates that matched whisking kinematics (∼1 Hz/1° protraction). Responses remained relatively unaffected when ipsilateral sensory feedback was removed by lidocaine but were reduced by optogenetically inhibiting the reticular nuclei.