Fluctuation analysis revealed two different modulatory mechanisms of cerebellar GABAergic transmission

Mar. 02, 2016

Computational analysis of fluctuation in neuronal membrane currents revealed previously unknown modulatory mechanisms of enhanced signal transmission in the cerebellum, according to research published March 1 in the open access journal PLOS ONE by Yumie Ono from Meiji University and colleagues from other institutions.

This study focuses on long-term potentiation (LTP), a cellular mechanism of learning, at GABAergic synapses on Purkinje cells in the cerebellum. LTP of the cerebellar Purkinje cell plays a crucial role in the regulation of motor coordination and motor learning in response to sensory inputs from the periphery and environment. Two types of LTP, a rebound potentiation (RP) and a purinoceptor-mediated LTP (PM-LTP), have previously been reported to occur at cerebellar GABAergic synapse on the Purkinje cell, however the detailed molecular mechanism underlying RP and PM-LTP has yet to be elucidated.

Ono and colleagues carried out a non-stationary fluctuation analysis that allows to predict computational model to estimate the number of active GABA receptors and the conductance of these receptors by measuring fluctuations of stimulation-evoked synaptic currents produced by a series of stimuli. This analysis was applied for determining the mechanisms underlying RP and PM-LTP at Purkinje cells' synapses. Their data demonstrated that the increase of signal transmission efficiency during RP mostly depends on the increased number in effective GABAA receptors, whereas PM-LTP is associated with the increase in current conductance of GABAA receptors without increasing their number. Pharmacological tests using inhibitors of cellular signal transduction also supported the involvement of different intracellular signaling pathways in these two types of LTP. Such distinct forms of synaptic plasticity could be beneficial for fine tuning of the cerebellar output from Purkinje cells, and this result would facilitate further understanding of the regulatory mechanism underlying motor coordination and learning.

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Citation: Ono Y, Saitow F, Konishi S. (2016) Differential modulation of GABAA receptors underlies postsynaptic depolarization- and purinoceptor-mediated enhancement of cerebellar inhibitory transmission: a nonstationary fluctuation analysis study. PLOS ONE 11(3): e0150636. doi:10.1371/journal.pone.0150636

Financial Disclosure: The present work has been funded by the Supported Program for the Strategic Research Foundation at Private University (2009-2013) from Ministry of Education, Culture, Sports, Science & Technology in Japan (MEXT).

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