Gating of long-term potentiation by nicotinic acetylcholine receptors at the cerebellum input stage

PLoS One. 2013 May 31;8(5):e64828. doi: 10.1371/journal.pone.0064828. Print 2013.

Abstract

The brain needs mechanisms able to correlate plastic changes with local circuit activity and internal functional states. At the cerebellum input stage, uncontrolled induction of long-term potentiation or depression (LTP or LTD) between mossy fibres and granule cells can saturate synaptic capacity and impair cerebellar functioning, which suggests that neuromodulators are required to gate plasticity processes. Cholinergic systems innervating the cerebellum are thought to enhance procedural learning and memory. Here we show that a specific subtype of acetylcholine receptors, the α7-nAChRs, are distributed both in cerebellar mossy fibre terminals and granule cell dendrites and contribute substantially to synaptic regulation. Selective α7-nAChR activation enhances the postsynaptic calcium increase, allowing weak mossy fibre bursts, which would otherwise cause LTD, to generate robust LTP. The local microperfusion of α7-nAChR agonists could also lead to in vivo switching of LTD to LTP following sensory stimulation of the whisker pad. In the cerebellar flocculus, α7-nAChR pharmacological activation impaired vestibulo-ocular-reflex adaptation, probably because LTP was saturated, preventing the fine adjustment of synaptic weights. These results show that gating mechanisms mediated by specific subtypes of nicotinic receptors are required to control the LTD/LTP balance at the mossy fibre-granule cell relay in order to regulate cerebellar plasticity and behavioural adaptation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cerebellum / physiology*
  • Long-Term Potentiation / drug effects
  • Long-Term Potentiation / physiology*
  • Mice
  • Nerve Fibers / drug effects
  • Nerve Fibers / physiology
  • Nicotinic Agonists / pharmacology
  • Rats
  • Receptors, Nicotinic / physiology*
  • Reflex, Vestibulo-Ocular / drug effects
  • Reflex, Vestibulo-Ocular / physiology
  • Synapses / physiology
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology
  • alpha7 Nicotinic Acetylcholine Receptor / physiology

Substances

  • Nicotinic Agonists
  • Receptors, Nicotinic
  • alpha7 Nicotinic Acetylcholine Receptor

Grant support

This work was supported by the European Union (CEREBNET FP7-ITN238686, REALNET FP7-ICT270434) and by a grant from the Italian Ministry of Health (RF-2008-1143418 and RF-2009-1475845) to ED. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.