Functional Expression of Nicotinic Acetylcholine Receptors in Rat Neocortical Layer 5 Pyramidal Cells

Neuronal nicotinic acetylcholine receptors (nAChRs) expressed by neurons of the neocortex are known to play a role in higher brain functions. Electrophysiological studies of neocortical neurons provided evidence that functional nAChRs are present on the axonal presynaptic terminals, on the somata and on dendrites of gamma-aminobutyric acid (GABA)ergic inhibitory interneurons. However, it is not clear if pyramidal neurons express functional postsynaptic nAChRs. Therefore, we investigated the action of locally applied acetylcholine (ACh) on layer 5 pyramidal neurons in the rat neocortex in vitro. In the presence of atropine, tetrodotoxin, glutamate receptor antagonists, and GABA(A) receptor antagonists, ACh induced membrane depolarizations which were generated by membrane inward currents consisting of a fast and a slow component. Analysis of the electrophysiological properties, the pharmacological characteristics, and the desensitization behavior of the 2 current components revealed that they were mediated by at least 2 different subtypes of the nAChR, most likely the alpha 7-like and the alpha 4 beta 2-like subtype. The expression of nAChRs in neocortical pyramidal cells raises the possibility that these neurons generate nicotinic excitatory postsynaptic potentials, thereby influencing cell excitability. Furthermore, because most nAChRs are permeable to calcium, they may modulate synaptic transmission and neuronal plasticity via a calcium-dependent postsynaptic mechanism.