Short-term facilitation and depression in the cerebellum: some observations on wild-type and mutant rodents deficient in the extracellular matrix molecule tenascin C

Date

2005-09-12

Advisors

Journal Title

Journal ISSN

ISSN

0077-8923

Volume Title

Publisher

Annals of the New York Academy of Sciences

Type

Article

Peer reviewed

Yes

Abstract

Short-term plasticity was studied on synapses to Purkinje cells (PC): paired-pulse facilitation in parallel fibers (PF) and paired-pulse depression in climbing fibers (CF). Both phenomena relate to synaptic strength. These forms of short-term plasticity were tested on cerebellar slices in rat by early postnatal synchronous stimulation of olivary neurons (i.e., CFs) with harmaline and by inhibition of a metabotropic glutamate receptor (mGluR) as well as in mice that were deficient in the extracellular matrix glycoprotein tenascin-C. Harmaline stimulation delayed the developmental competition between CF inputs and maintained multiple innervation. Paired-pulse depression of the CF-PC synapse after harmaline treatment was more expressed. However, paired-pulse facilitation in PF-PC synapses remained unchanged. Electrophysiological responses of postsynaptic mGluR1 in CF-PC synapses could be obtained only with AMPA receptors blocked and glutamate uptake impaired. The mGluR1-specific antagonist CPCCOEt suppressed the CF-mGluR EPSC in some PCs and potentiated it in other PCs. CF paired-pulse depression was not changed with CPCCOEt, thus excluding a presynaptic effect. The postsynaptic effect was underlined by CPCCOEt-induced rise in amplitude of EPSC and by a prolongation of its decay time. Tenascins are extracellular matrix glycoproteins that may restrict the regenerative capacity of the nervous tissue. Testing short-term presynaptic plasticity in tenascin-C-deficient mice showed that CF paired-pulse depression was less expressed while PF paired-pulse facilitation was augmented except in a group of cells where there was even depression. The results underline differences in forms of short-term plasticity with regard to susceptibility to diverse modulatory factors.

Description

Keywords

cerebellum, Purkinje cell, short-term plasticity, tenascin, metabotropic glutamate receptor

Citation

Andjus, P.R. et al. (2005) Short-term facilitation and depression in the cerebellum: some observations on wild-type and mutant rodents deficient in the extracellular matrix molecule tenascin C. Annals of the New York Academy of Sciences, 1048, pp. 185-197.

Rights

Research Institute

Leicester Institute for Pharmaceutical Innovation - From Molecules to Practice (LIPI)