Title : Involvement of Nicotinic and Muscarinic Receptors in the Endogenous Cholinergic Modulation of the Balance between Excitation and Inhibition in the Young Rat Visual Cortex
Authors : Estelle Lucas-Meunier, Cyril Monier, Muriel Amar, Gérard Baux, Yves Frégnac and Philippe Fossier
Year : 2009
Journal : Cerebral Cortex
Volume : 19
Pages : 2411-2427
This study aims to clarify how endogenous release of cortical acetylcholine (ACh) modulates the balance between excitation and inhibition evoked in visual cortex. We show that electrical stimulation in layer 1 produced a signi?cant release of ACh measured intracortically by chemoluminescence and evoked a composite synaptic response recorded intracellularly in layer 5 pyramidal neurons of rat visual cortex. The pharmacological speci?city of the ACh neuromodulation was determined from the continuous whole-cell voltage clamp measurement of stimulation- locked changes of the input conductance during the application of cholinergic agonists and antagonists. Blockade of glutamatergic and g-aminobutyric acid (GABAergic) receptors suppressed the evoked response, indicating that stimulation-induced release of ACh does not directly activate a cholinergic synaptic conductance in recorded neurons. Comparison of cytisine and mecamylamine effects on nicotinic receptors showed that excitation is enhanced by endogenous evoked release of ACh through the presynaptic activation of a* b4 receptors located on glutamatergic ?bers. DHbE, the selective a4b2 nicotinic receptor antagonist, induced a depression of inhibition. Endogenous ACh could also enhance inhibition by acting directly on GABAergic interneurons, presynaptic to the recorded cell. We conclude that endogenous-released ACh ampli?es the dominance of the inhibitory drive and thus decreases the excitability and sensory responsiveness of layer 5 pyramidal neurons.