We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Loss of Muscarinic Autoreceptor Function Impairs Long- Term Depression But Not Long-Term Potentiation in the Striatum.
- Authors
Bonsi, Paola; Martella, Giuseppina; Cuomo, Dario; Platania, Paola; Sciamanna, Giuseppe; Bernardi, Giorgio; Wess, Jürgen; Pisani, Antonio
- Abstract
Muscarinic autoreceptors regulate cholinergic tone in the striatum. We investigated the functional consequences of genetic deletion of striatal muscarinic autoreceptors by means of electrophysiological recordings from either medium spiny neurons (MSNs) or cholinergic interneurons (ChIs) in slices from single M4 or double M2/M4 muscarinic acetylcholine receptor (mAChR) knock-out (-/-) mice. In control ChIs, the muscarinic agonist oxotremorine (300 nM) produced a self-inhibitory outward current that was mostly reduced in M4-/- and abolished in M2/M4-/- mice, suggesting an involvement of both M2 and M4 autoreceptors. In MSNs from both M4-/- and M2/M4-/- mice, muscarine caused a membrane depolarization that was prevented by the M1 receptor-preferring antagonist pirenzepine (100 nM), suggesting that M1 receptor function was unaltered. Acetylcholine has been involved in striatal long-term potentiation (LTP) or long-term depression (LTD) induction. Loss of muscarinic autoreceptor function is predicted to affect synaptic plasticity by modifying striatal cholinergic tone. Indeed, high-frequency stimulation of glutamatergic afferents failed to induce LTD in MSNs from both M4-/- and M2/M4-/- mice, as well as in wild-type mice pretreated with the M2/M4 antagonist AF-DX384 (11-[[2-[(diethylamino)methyl]-1-piperidinyl]acetyl]-5,1 1-dihydro-6H-pyrido[2,3b][1,4] benzodiazepin-6-one). Interestingly, LTD could be restored by either pirenzepine (100nM) or hemicholinium-3 (10 μM), a depletor of endogenous ACh. Conversely, LTP induction did not show any difference among the three mouse strains and was prevented by pirenzepine. These results demonstrate that M2/M4 muscarinic autoreceptors regulate ACh release from striatal ChIs. As a consequence, endogenous ACh drives the polarity of bidirectional synaptic plasticity.
- Subjects
MUSCARINIC receptors; NEUROPLASTICITY; MICE; PIRENZEPINE; ANIMAL models in research; SCIENTIFIC method
- Publication
Journal of Neuroscience, 2008, Vol 28, Issue 24, p6258
- ISSN
0270-6474
- Publication type
Article
- DOI
10.1523/JNEUROSCI.1678-08.2008