Regulation of rat mesencephalic GABAergic neurones through muscarinic receptors

• Published in: The Journal of physiology Vol. 556; no. 2; pp. 429 - 445
• Main Authors: Michel, François J., Robillard, Julie M., Trudeau, Louis‐Éric
• Format: Journal Article
• Language: English
• Published: 9600 Garsington Road , Oxford , OX4 2DQ , UK The Physiological Society 15.04.2004; Blackwell Science Ltd; Blackwell Science Inc
• Subjects: Acetylcholine - pharmacology; Action Potentials - drug effects; Action Potentials - physiology; Animals; Calcium - metabolism; Cells, Cultured; Dose-Response Relationship, Drug; gamma-Aminobutyric Acid - physiology; Mesencephalon - cytology; Muscarine - pharmacology; Muscarinic Agonists - pharmacology; Muscarinic Antagonists - pharmacology; Neural Inhibition - physiology; Neurons - cytology; Neurons - physiology; Piperidines - pharmacology; Potassium Channels, Voltage-Gated - physiology; Rats; Rats, Sprague-Dawley; Receptor, Muscarinic M3 - agonists; Receptor, Muscarinic M3 - antagonists & inhibitors; Receptor, Muscarinic M3 - physiology; Research Papers; Synapses - physiology
• ISSN: 0022-3751; 1469-7793
• DOI: 10.1113/jphysiol.2003.057737

Central dopamine neurones are involved in regulating cognitive and motor processes. Most of these neurones are located in the ventral mesencephalon where they receive abundant intrinsic and extrinsic GABAergic input. Cholinergic neurones, originating from mesopontine nuclei, project profusely in the mesencephalon where they preferentially synapse onto local GABAergic neurones. The physiological role of this cholinergic innervation of GABAergic neurones remains to be determined, but these observations raise the hypothesis that ACh may regulate dopamine neurones indirectly through GABAergic interneurones. Using a mesencephalic primary culture model, we studied the impact of cholinergic agonists on mesencephalic GABAergic neurones. ACh increased the frequency of spontaneous IPSCs (151 ± 49%). Selective activation of muscarinic receptors increased the firing rate of isolated GABAergic neurones by 67 ± 13%. The enhancement in firing rate was Ca 2+ dependent since inclusion of BAPTA in the pipette blocked it, actually revealing a decrease in firing rate accompanied by membrane hyperpolarization. This inhibitory action was prevented by tertiapin, a blocker of GIRK-type K + channels. In addition to its excitatory somatodendritic effect, activation of muscarinic receptors also acted presynaptically, inhibiting the amplitude of unitary GABAergic synaptic currents. Both the enhancement in spontaneous IPSC frequency and presynaptic inhibition were abolished by 4-DAMP (100 n m ), a preferential M3 muscarinic receptor antagonist. The presence of M3-like receptors on mesencephalic GABAergic neurones was confirmed by immunocytochemistry. Taken together, these results demonstrate that mesencephalic GABAergic neurones can be regulated directly through muscarinic receptors. Our findings provide new data that should be helpful in better understanding the influence of local GABAergic neurones during cholinergic activation of mesencephalic circuits.