Adenylyl cyclase type 5 contributes to corticostriatal plasticity and striatum-dependent learning.
J Neurosci
; 29(39): 12115-24, 2009 Sep 30.
Article
in En
| MEDLINE
| ID: mdl-19793969
ABSTRACT
Dopamine (DA)-dependent corticostriatal plasticity is thought to underlie incremental procedural learning. A primary effector of striatal DA signaling is cAMP, yet its role in corticostriatal plasticity and striatum-dependent learning remains unclear. Here, we show that genetic deletion of a striatum-enriched isoform of adenylyl cyclase, AC5 knock-out (AC5KO), impairs two forms of striatum-dependent learning and corticostriatal synaptic plasticity. AC5KO mice were severely impaired in acquisition of a response strategy in the cross maze, a striatum-dependent task requiring a correct body turn to find a goal arm. In addition, AC5KO mice were impaired in acquisition of a motor skill, as assessed by the accelerated rotarod. Slice electrophysiology revealed a deficit in corticostriatal long-term depression (LTD) after high-frequency stimulation of tissue from AC5KO mice. LTD was rescued by activation of either presynaptic cannabinoid type 1 (CB(1)) receptors or postsynaptic metabotropic glutamate receptors (mGluRs), suggesting a postsynaptic role of AC5-cAMP, upstream of endocannabinoid release. In striatopallidal-projecting medium spiny neurons, DA D(2) receptors are negatively coupled to cAMP production, and activation of these receptors is required for endocannabinoid release and corticostriatal LTD. Recordings from striatopallidal neurons indicated that this is mediated by AC5, because coactivation of D(2) and mGluRs could induce LTD in wild-type but not in AC5KO neurons. To further examine the role of cAMP in corticostriatal plasticity, we elevated cAMP in striatal neurons of wild-type mice via the recording electrode. Under these conditions, corticostriatal LTD was eliminated. Together, these data suggest an AC5-cAMP-endocannabinoid-CB(1) signaling pathway in corticostriatal plasticity and striatum-dependent learning.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Cerebral Cortex
/
Adenylyl Cyclases
/
Corpus Striatum
/
Isoenzymes
/
Learning
/
Neuronal Plasticity
Limits:
Animals
Language:
En
Journal:
J Neurosci
Year:
2009
Type:
Article
Affiliation country:
United States