title: Gating of long-term potentiation by nicotinic acetylcholine receptors at the cerebellum input stage.
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.
authors.affiliation: Brain Connectivity Center, C. Mondino National Institute of Neurology Foundation, IRCCS, Pavia, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Prestori
authors.forename: Claudia
authors.initials: C
authors.lastname: Bonardi
authors.forename: Lisa
authors.initials: L
authors.lastname: Mapelli
authors.forename: Paola
authors.initials: P
authors.lastname: Lombardo
authors.forename: Rianne
authors.initials: R
authors.lastname: Goselink
authors.forename: Maria Egle
authors.initials: ME
authors.lastname: De Stefano
authors.forename: Daniela
authors.initials: D
authors.lastname: Gandolfi
authors.forename: Jonathan
authors.initials: J
authors.lastname: Mapelli
authors.forename: Daniel
authors.initials: D
authors.lastname: Bertrand
authors.forename: Martijn
authors.initials: M
authors.lastname: Schonewille
authors.forename: Chris
authors.initials: C
authors.lastname: De Zeeuw
authors.forename: Egidio
authors.initials: E
authors.lastname: D'Angelo
mesh_terms: D000818:Animals; D002531:Cerebellum / Q000502:physiology*; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D009412:Nerve Fibers / Q000187:drug effects / Q000502:physiology; D018722:Nicotinic Agonists / Q000494:pharmacology; D051381:Rats; D011978:Receptors, Nicotinic / Q000502:physiology*; D012027:Reflex, Vestibulo-Ocular / Q000187:drug effects / Q000502:physiology; D013569:Synapses / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D064569:alpha7 Nicotinic Acetylcholine Receptor / Q000502:physiology
chemical_list: D018722:Nicotinic Agonists; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor