Abstract:
:Convergent lines of evidence have recently highlighted β3-adrenoreceptors (ARs) as a potentially critical target in the regulation of nervous and behavioral functions, including memory consolidation, anxiety, and depression. Nevertheless, the role of β3-ARs in the cerebellum has been never investigated. To address this issue, we first examined the effects of pharmacological manipulation of β3-ARs on motor learning in mice. We found that blockade of β3-ARs by SR 59230A impaired the acquisition of the rotarod task with no effect on general locomotion. Since the parallel fiber-Purkinje cell (PF-PC) synapse is considered to be the main cerebellar locus of motor learning, we assessed β3-AR modulatory action on this synapse as well as its expression in cerebellar slices. We demonstrate, for the first time, a strong expression of β3-ARs on Purkinje cell soma and dendrites. In addition, whole-cell patch-clamp recordings revealed that bath application of β3-AR agonist CL316,243 depressed the PF-PC excitatory postsynaptic currents via a postsynaptic mechanism mediated by the PI3K signaling pathway. Application of CL316,243 also interfered with the expression of PF long-term potentiation, whereas SR 59230A prevented the induction of LTD at PF-PC synapse. These results underline the critical role of β3-AR on cerebellar synaptic transmission and plasticity and provide a new mechanism for adrenergic modulation of motor learning.
journal_name
J Neurosci Resjournal_title
Journal of neuroscience researchauthors
Lippiello P,Hoxha E,Cristiano C,Malvicini E,Stanley A,Russo R,Tempia F,Miniaci MCdoi
10.1002/jnr.24712subject
Has Abstractpub_date
2020-11-01 00:00:00pages
2263-2274issue
11eissn
0360-4012issn
1097-4547journal_volume
98pub_type
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