Affiliation:
1. Montreal Neurological Institute and Departments of Neurology and Neurosurgery and of Physiology, McGill University, Montreal, Quebec H3A 2B4 Canada; and
2. Centro per l'Epilessia, Ospedale San Paolo, Università degli Studi di Milano, 20142 Milan, Italy
Abstract
Acetylcholine functions as a neuromodulator in the mammalian brain by binding to specific receptors and thus bringing about profound changes in neuronal excitability. Activation of muscarinic receptors often results in an increased excitability of cortical cells. It is, however, unknown whether such an action is present in the subiculum, a limbic structure that may be involved in cognitive processes as well as in seizure propagation. Most rat subicular neurons are endowed of intrinsic membrane properties that make them fire action potential bursts. Using intracellular recordings from these bursting cells in a slice preparation, we report here that application of the cholinergic agonist carbachol (CCh, 30–100 μM) to medium containing ionotropic excitatory amino acid receptor antagonists reduces burst-afterhyperpolarizations (burst-AHPs) and discloses depolarizing plateau potentials that outlast the triggering current pulses by 140–2,800 ms. These plateau potentials appear with CCh concentrations >50 μM and are dependent on the resting membrane potential and on the intensity/duration of the triggering pulse; are recorded during application of tetrodotoxin (1 μM, n = 5 neurons); but are markedly reduced by replacing 82% of extracellular Na+with equimolar choline ( n = 6). Plateau potentials also are abolished by Co2+ (2 mM; n = 5) or Cd2+ (1 mM; n = 2) application and by recording with electrodes containing the Ca2+chelator bis(2-aminophenoxy)ethane- N, N,N′,N′-tetraacetic acid (0.2 M; n = 6). CCh-induced burst-AHP reduction and plateau potentials are reversed by the muscarinic antagonist atropine (0.5 μM, n = 7). In conclusion, our findings demonstrate a powerful muscarinic modulation of the intrinsic excitability of subicular bursting cells that is predominated by the appearance of plateau potentials. These changes in excitability may contribute to physiological processes such as learning or memory and play a role in the generation of epileptiform depolarizations. We propose that, as in other limbic structures, muscarinic plateau potentials in the subiculum are mainly due to a Ca2+-dependent nonselective cationic conductance.
Publisher
American Physiological Society
Subject
Physiology,General Neuroscience
Cited by
43 articles.
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