Striatal Muscarinic Receptors Promote Activity Dependence of Dopamine Transmission via Distinct Receptor Subtypes on Cholinergic Interneurons in Ventral versus Dorsal Striatum

• DOI: 10.1523/jneurosci.5620-09.2010
• Publication Date: 2010-03-04T16:06:35Z
• Authors: Sarah Threlfell; Michael A. Clements; Tansi Khodai; Ilse S. Pienaar; Richard Exley; Jürgen Wess; Stephanie J. Cragg
• Keywords: Oxotremorine; Eticlopride

Striatal dopamine (DA) and acetylcholine (ACh) regulate motivated behaviors striatal plasticity. Interactions between these neurotransmitters may be important, through synchronous changes in parent neuron activities reciprocal presynaptic regulation of release. How DA signaling is regulated by muscarinic receptors (mAChRs) unresolved; contradictory reports indicate suppression or facilitation, implicating several mAChR subtypes on various neurons. We investigated whether varies with activity identified the mAChRs responsible sensorimotor- versus limbic-associated striatum. detected real time at carbon fiber microelectrodes mouse slices. Broad-spectrum agonists [oxotremorine-M, APET (arecaidine propargyl ester tosylate)] decreased release evoked low-frequency stimuli (1–10 Hz, four pulses) but increased sensitivity to activity, even enhancing high frequencies (e.g., >25 Hz for pulses). These bidirectional effects depended ACh input nicotinic (nAChRs) axons not GABA glutamate input. In caudate–putamen (CPu), knock-out M 2 - 4 -mAChRs (not 5 ) prevented control DA, indicating that are required. nucleus accumbens (NAc) core shell, function was -knock-outs, -knock-outs. data mAChRs, inhibiting from cholinergic interneurons thus modifying nAChR offer variable probability promotes how reflects activation dopaminergic axons. Furthermore, different coupling /M CPu NAc suggests targets influence DA/ACh differentially domains.