The Emerging Concept of Intrinsic Plasticity: Activity-dependent Modulation of Intrinsic Excitability in Cerebellar Purkinje Cells and Motor Learning

Abstract

What is memory? How does the brain process the sensory information and modify an organism's behavior? Many neuroscientists have focused on the activity- and experience-dependent modifications of synaptic functions in order to solve these fundamental questions in neuroscience. Recently, the plasticity of intrinsic excitability (called intrinsic plasticity) has emerged as an important element for information processing and storage in the brain. As the cerebellar Purkinje cells are the sole output neurons in the cerebellar cortex and the information is conveyed from a neuron to its relay neurons by forms of action potential firing, the modulation of the intrinsic firing activity may play a critical role in the cerebellar learning. Many voltage-gated and/or Ca2+-activated ion channels are involved in shaping the spiking output as well as integrating synaptic inputs to finely tune the cerebellar output. Recent studies suggested that the modulation of the intrinsic excitability and its plasticity in the cerebellar Purkinje cells might function as an integrator for information processing and memory formation. Moreover, the intrinsic plasticity might also determine the strength of connectivity to the sub-cortical areas such as deep cerebellar nuclei and vestibular nuclei to trigger the consolidation of the cerebellar-dependent memory by transferring the information.

Homeostatic cerebellar compensation of age-related changes of vestibulo-ocular reflex adaptation: a computational epidemiology study

“…GCs generated a sparse representation of the MF inputs and they transmitted the encoded sensory information to 200 Purkinje cells (PCs), through excitatory projections. An intrinsic plasticity mechanism (Jang et al, 2020, Shim et al, 2018 regulated the excitability of model PCs, consistently with electrophysiological recordings (Shim et al, 2017, Turrigiano et al, 1994) (see Methods). PCs integrated the afferent signals from PFs (i.e., the axons of GCs), which elicited Purkinje simple spikes signal from climbing fibres (CFs), i.e., the axons of inferior olive (IO) cells.…”

“…It has been suggested that neural compensatory retina slips during gaze stabilisation (i.e., error signalling), we evaluated to what extent age-related changes in the electrical coupling of inferior olive neurons could impact the VOR function. (ii) Intrinsic plasticity occurring at Purkinje cell synapses (Jang et al, 2020, Shim et al, 2018, which regulates the excitability of Purkinje neurons (by modulating their membrane capacitance) to adapt their response to synaptic morphological changes (Zhang et al, 2010, Andersen et al, 2003. We investigated the possible role of intrinsic plasticity at Purkinje cell synapses as a local homeostatic process, i.e., compensating for decreasing levels of vestibular afferent signals (which reach Purkinje cells through cerebellar granule cells) as well as for electro-responsiveness changes induced by ageing in Purkinje cells themselves (Zhang et al, 2010, Andersen et al, 2003.…”

Modification of Synaptic-Input Clustering by Intrinsic Excitability Plasticity on Cerebellar Purkinje Cell Dendrites

“…Details are described in Materials and Methods. Lewis and Raman, 2014;Shim et al, 2018). Recent studies on the heterogeneous excitability among dendritic branches, through mechanisms underlain by BK, SK, and A-type K ϩ -channels (Rancz and Häusser, 2006;Ohtsuki et al, 2012b;Otsu et al, 2014;Ohtsuki and Hansel, 2018;Zang et al, 2018), argue against the uniform pattern of the intrinsic excitability of dendritic branches.…”

Synaptic and intrinsic plasticity coordinate spike output in cerebellar Purkinje cells

“…Cerebellar PC intrinsic plasticity has been implicated as a neural computational feature of the information processing of cerebellar cortex (Belmeguenai et al, 2010;Grassi and Pettorossi, 2001;Shim et al, 2018Shim et al, , 2017Steuber et al, 2007). Notably, bidirectional modulation of synaptic plasticity at the PF-PC synapses has been found to be accompanied by intrinsic plasticity, which shows the same polarity with synaptic plasticity, indicating that the intrinsic plasticity might synergistically enable the PC spike output to be sufficiently modulated when synaptic plasticity occurs (Belmeguenai et al, 2010;Shim et al, 2017).…”

“…Emerging evidence has revealed that learning and memory is implemented not only by activitydependent synaptic plasticity but also by non-synaptic intrinsic plasticity in several neural circuits (Crestani et al, 2018;Lisman et al, 2018;Shim et al, 2018;Zhang and Linden, 2003). Of interest, intrinsic excitability contributes to integration of synaptic inputs and generation of net neuronal output (Hoffman et al, 1997;Lev-Ram et al, 2003, 1995Shim et al, 2017).…”