In vivo analysis of synaptic activity in cerebellar nuclei neurons unravels the efficacy of excitatory inputs

Abstract

It is commonly agreed that the main function of the cerebellar system is to provide well-timed signals used for the execution of motor commands or prediction of sensory inputs. This function is manifested as a temporal sequence of spiking that should be expressed in the cerebellar nuclei (CN) projection neurons. Whether spiking activity is generated by excitation or release from inhibition is still a hotly debated issue. In an attempt to resolve this debate, we recorded intracellularly from CN neurons in anaesthetized mice and performed an analysis of synaptic activity that yielded a number of important observations. First, we demonstrate that CN neurons can be classified into four groups. Second, shape-index plots of the excitatory events suggest that they are distributed over the entire dendritic tree. Third, the rise time of excitatory events is linearly related to amplitude, suggesting that all excitatory events contribute equally to the generation of action potentials (APs). Fourth, we identified a temporal pattern of spontaneous excitatory events that represent climbing fibre inputs and confirm the results by direct stimulation and analysis on harmaline-evoked activity. Finally, we demonstrate that the probability of excitatory inputs generating an AP is 0.1 yet half of the APs are generated by excitatory events. Moreover, the probability of a presumably spontaneous climbing fibre input generating an AP is higher, reaching a mean population value of 0.15. In view of these results, the mode of synaptic integration at the level of the CN should be re-considered.

Long-Lasting Response Changes in Deep Cerebellar Nuclei in vivo Correlate With Low-Frequency Oscillations

“…Deep cerebellar nuclei neurons are autorhythmic ( Jahnsen, 1986a , b ) and receive both excitatory inputs from collaterals of mossy and climbing fibers and inhibitory inputs from Purkinje cells (PCs) ( Llinas and Muhlethaler, 1988 ). DCN neurons respond to tactile stimulation generating discharge patterns, which reflect the combination of inhibitory and excitatory inputs ( Rowland and Jaeger, 2005 , 2008 ; Chen et al, 2010 ; Canto et al, 2016 ; Yarden-Rabinowitz and Yarom, 2017 ). DCN neurons send output fibers to thalamus and to various precerebellar nuclei, influencing neuronal activity both in descending systems and in the cerebral cortex ( Watson et al, 2014 ; Gao et al, 2018 ).…”

High glucose upregulates myosin light chain kinase to induce microfilament cytoskeleton rearrangement in hippocampal neurons

“…Neuronal plasticity serves a role in the brain and refers to morphological, biochemical and physiological alterations in the developing nervous system. Accumulating evidence indicates that alterations in synaptic contacts modulate the function of the nervous system ( 21 , 22 ).…”

Modulatory Effects of Monoamines and Perineuronal Nets on Output of Cerebellar Purkinje Cells

“…Furthermore, it is involved in the formation of excitatory synaptic long-term potentiation (LTP) of transmission between mossy fibers onto large DCN neurons ( Racine et al, 1986 ; Pugh and Raman, 2006 , 2008 ; Person and Raman, 2010 ). The LTP has been thought to contribute to facilitating firing of large neurons in the DCN ( Wu and Raman, 2017 ; Yarden-Rabinowitz and Yarom, 2017 ), and to be one of critical synaptic mechanisms underlying cerebellar motor learning, including ocular reflex adaptation ( Miles and Lisberger, 1981 ; Kassardjian et al, 2005 ; Shutoh et al, 2006 ; Okamoto et al, 2011 ) and delay eyeblink conditioning ( Krupa et al, 1993 ; Medina and Mauk, 1999 ; Attwell et al, 2002 ; Christian and Thompson, 2003 ; Kistler and De Zeeuw, 2003 ; Wetmore et al, 2008 ).…”