Localization of Presynaptic Plasticity Mechanisms Enables Functional Independence of Synaptic and Ectopic Transmission in the Cerebellum.

Katharine L Dobson,Tomas C Bellamy

doi:10.1155/2015/602356

Abstract

In the cerebellar molecular layer parallel fibre terminals release glutamate from both the active zone and from extrasynaptic “ectopic” sites. Ectopic release mediates transmission to the Bergmann glia that ensheathe the synapse, activating Ca2+-permeable AMPA receptors and glutamate transporters. Parallel fibre terminals exhibit several forms of presynaptic plasticity, including cAMP-dependent long-term potentiation and endocannabinoid-dependent long-term depression, but it is not known whether these presynaptic forms of long-term plasticity also influence ectopic transmission to Bergmann glia. Stimulation of parallel fibre inputs at 16 Hz evoked LTP of synaptic transmission, but LTD of ectopic transmission. Pharmacological activation of adenylyl cyclase by forskolin caused LTP at Purkinje neurons, but only transient potentiation at Bergmann glia, reinforcing the concept that ectopic sites lack the capacity to express sustained cAMP-dependent potentiation. Activation of mGluR1 caused depression of synaptic transmission via retrograde endocannabinoid signalling but had no significant effect at ectopic sites. In contrast, activation of NMDA receptors suppressed both synaptic and ectopic transmission. The results suggest that the signalling mechanisms for presynaptic LTP and retrograde depression by endocannabinoids are restricted to the active zone at parallel fibre synapses, allowing independent modulation of synaptic transmission to Purkinje neurons and ectopic transmission to Bergmann glia.

Highlights

In the cerebellar cortex, transmission from parallel and climbing fibre terminals to Bergmann glial cells occurs at dedicated release sites that are “ectopic” to the presynaptic active zone [1, 2]
The results indicate that induction and maintenance of presynaptic plasticity is localized to the active zone sites, and ectopic transmission to glia is largely insensitive to the signalling pathways associated with both long-term potentiation (LTP) and retrograde initiation of long-term depression (LTD)
Presynaptic LTP Is Absent at Ectopic Sites

Summary

Introduction

Transmission from parallel and climbing fibre terminals to Bergmann glial cells occurs at dedicated release sites that are “ectopic” to the presynaptic active zone [1, 2]. At the parallel fibre, paired pulse stimulation causes facilitation of excitatory postsynaptic currents (EPSCs) for the second pulse, a phenomenon attributed to summation of presynaptic calcium levels increasing release probability at the terminal [3]. This is true for both synaptic and ectopic transmission, but ectopic sites show a greater degree of facilitation than synaptic sites (5-fold versus 2-fold [4, 5]). Ectopic sites mirror the synaptic response, but with a more profound and longer-lasting depression (0.1fold versus 0.5-fold [4])

Objectives

Results

Conclusion