Differential Coding Strategies in Glutamatergic and GABAergic Neurons in the Medial Cerebellar Nucleus

Abstract

The cerebellum drives motor coordination and sequencing of actions at the millisecond timescale through adaptive control of cerebellar nuclear output. Cerebellar nuclei integrate high-frequency information from both the cerebellar cortex and the two main excitatory inputs of the cerebellum: the mossy fibers and the climbing fiber collaterals. However, how nuclear cells process rate and timing of inputs carried by these inputs is still debated. Here, we investigate the influence of the cerebellar cortical output, the Purkinje cells, on identified cerebellar nuclei neurons in vivo in male mice. Using transgenic mice expressing Channelrhodopsin2 specifically in Purkinje cells and tetrode recordings in the medial nucleus, we identified two main groups of neurons based on the waveform of their action potentials. These two groups of neurons coincide with glutamatergic and GABAergic neurons identified by optotagging after Chrimson expression in VGLUT2-cre and GAD-cre mice, respectively. The glutamatergic-like neurons fire at high rate and respond to both rate and timing of Purkinje cell population inputs, whereas GABAergic-like neurons only respond to the mean population firing rate of Purkinje cells at high frequencies. Moreover, synchronous activation of Purkinje cells can entrain the glutamatergic-like, but not the GABAergic-like, cells over a wide range of frequencies. Our results suggest that the downstream effect of synchronous and rhythmic Purkinje cell discharges depends on the type of cerebellar nuclei neurons targeted.

Abnormal cerebellar function and tremor in a mouse model for non‐manifesting partially penetrant dystonia type 6

“…The excitatory nuclei neurons have a higher firing frequency (Özcan et al . 2020) and a larger cell body (Uusisaari et al . 2007) compared to the inhibitory neurons.…”

Modular output circuits of the fastigial nucleus for diverse motor and nonmotor functions of the cerebellar vermis

“…Purkinje cells with the fastest firing capacity (Aldoc-negative: Xiao et al, 2014 ; Zhou et al, 2014 ) densely innervate the largest fastigial neurons (F1 R ), which in turn make extensive synapses onto somata and proximal dendrites of gigantic brainstem neurons responsible for rapid posturomotor reflexes ( Eccles et al, 1975a ). The largest glutamatergic fastigial cell types can transform Purkinje cell synaptic inhibition into precisely timed spikes ( Özcan et al, 2020 ), as has been shown for their counterparts in the interpositus and dentate nuclei ( Person and Raman, 2012 ). On the other hand, physiological properties of the smallest glutamatergic fastigial cell types (F3 and F4) have not been explicitly reported, likely reflecting challenges in isolating and targeting them for recordings.…”

Widespread inhibitory projections from the cerebellar interposed nucleus

“…These studies assume that premotor and nucleo-olivary neurons respond in roughly equivalent ways during behavior (Shadmehr, 2020). Differences in the intrinsic and synaptic properties of these neurons, however, raise the likelihood that this prediction may not be realized Najac & Raman, 2017;Özcan et al, 2020;Uusisaari & Knöpfel, 2008;Uusisaari et al, 2007;Uusisaari & Knöpfel, 2011). Moreover, our data suggest different cell types also differ in their input sources, further predicting diverse response properties.…”