Diverse Precerebellar Neurons Share Similar Intrinsic Excitability

Abstract

The cerebellum dedicates a majority of the brain’s neurons to processing a wide range of sensory, motor, and cognitive signals. Stereotyped circuitry within the cerebellar cortex suggests that similar computations are performed throughout the cerebellum, but little is known about whether diverse precerebellar neurons are specialized for the nature of the information they convey. In vivo recordings indicate that firing responses to sensory or motor stimuli vary dramatically across different precerebellar nuclei, but whether this reflects diverse synaptic inputs or differentially tuned intrinsic excitability has not been determined. We targeted whole-cell patch clamp recordings to neurons in 8 precerebellar nuclei which were retrogradely labeled from different regions of the cerebellum in mice. Intrinsic physiology was compared across neurons in the medial vestibular, external cuneate, lateral reticular, prepositus hypoglossi, supragenual, Roller/intercalatus, reticularis tegmenti pontis (NRTP), and pontine nuclei. Within the firing domain, precerebellar neurons were remarkably similar. Firing faithfully followed temporally modulated inputs, could be sustained at high rates, and was a linear function of input current over a wide range of inputs and firing rates. Pharmacological analyses revealed common expression of Kv3 currents, which were essential for a wide linear firing range, and of SK currents, which were essential for a wide linear input range. In contrast, membrane properties below spike threshold varied considerably within and across precerebellar nuclei, as evidenced by variability in postinhibitory rebound firing. Our findings indicate that diverse precerebellar neurons perfom similar scaling computations on their inputs but may be differentially tuned to synaptic inhibition.

Implementation of Linear Sensory Signaling via Multiple Coordinated Mechanisms at Central Vestibular Nerve Synapses

“…Several mechanistic implementations that promote adequate vesicle availability at vestibular synapses have been observed in other fast-firing neurons in the cerebral cortex, hippocampus, cerebellum, and brainstem (Crowley et al, 2007; Hallermann and Silver, 2013; Hu et al, 2014). Rapid repolarization of presynaptic action potentials by Kv3 currents (Gittis et al, 2010; Kolkman et al, 2011; Rudy and McBain, 2001) minimizes Ca2+ influx and reduces P R (Geiger and Jonas, 2000; Ritzau-Jost et al, 2014; Sabatini and Regehr, 1997; Taschenberger and von Gersdorff, 2000; Telgkamp et al, 2004). Large vesicle pools, multiple release sites, and rapid kinetics of vesicle translocation, docking, and priming maintain vesicle availability during high-rate transmission.…”

Facilitation of mossy fibre‐driven spiking in the cerebellar nuclei by the synchrony of inhibition

“…Since mossy fibres are heterogeneous and may differ physiologically (Kolkman et al . ; Chabrol et al . ), the stimulation electrode was positioned as consistently as possible to maximize replicability and reliability.…”

Neuronal Classification and Marker Gene Identification via Single-Cell Expression Profiling of Brainstem Vestibular Neurons Subserving Cerebellar Learning

“…Although initial in vitro recordings classified MVN neurons into 2 types on the basis of action potential waveforms (Serafin et al, 1991; Johnston et al, 1994), subsequent studies demonstrated that intrinsic physiological properties are distributed continuously rather than bimodally (du Lac and Lisberger 1995; Bagnall et al 2007). Many studies have now demonstrated specific differences in intrinsic excitability across MVN neurons with different axonal projections (Sekirnjak et al, 2006; Kolkman et al, 2011a and 2011b) and/or transmitter expression (Takazawa et al, 2004; Bagnall et al, 2007; Shin et al, 2011). The observation that Purkinje cells differentially innervate the somata and dendrites of several types of MVN neurons (Sekirnjak et al, 2003; Shin et al, 2011) complicates analyses of cerebellar learning.…”