Muscarinic receptor activation induces depolarizing plateau potentials in bursting neurons of the rat subiculum

Muscarinic receptor activation induces depolarizing plateau potentials in b ursting neurons of the rat subiculum. J. Neurophysiol. 82: 2590-2601, 1999. Acetylcholine functions as a neuromodulator in the mammalian brain by bind ing to specific receptors and thus bringing about profound changes in neuro nal excitability. Activation of muscarinic receptors often results in an in creased excitability of cortical cells. It is, however, unknown whether suc h an action is present in the subiculum, a limbic structure that may be inv olved in cognitive processes as well as in seizure propagation. Most rat su bicular neurons are endowed of intrinsic membrane properties that make them fire action potential bursts. Using intracellular recordings from these bu rsting cells in a slice preparation, we report here that application of the cholinergic agonist carbachol (CCh, 30-100 mu M) to medium containing iono tropic excitatory amino acid receptor antagonists reduces burst-afterhyperp olarizations (burst-AHPs) and discloses depolarizing plateau potentials tha t outlast the triggering current pulses by 140-2,800 ms. These plateau pote ntials appear with CCh concentrations >50 mu M and are dependent on the res ting membrane potential and on the intensity/duration of the triggering pul se; are recorded during application of tetrodotoxin (1 mu M, n = 5 neurons) ; but are markedly reduced by replacing 82% of extracellular Na+ with equim olar 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 c ontaining the Ca2+ chelator bis(2-aminophenoxy)ethane-N, N,N',N'-tetraaceti c acid (0.2 M; n = 6). CCh-induced burst-AHP reduction and plateau potentia ls are reversed by the muscarinic antagonist atropine (0.5 mu M, n = 7). In conclusion, our findings demonstrate a powerful muscarinic modulation of t he 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, a s in other limbic structures, muscarinic plateau potentials in the subiculu m are mainly due to a Ca2+-dependent nonselective cationic conductance.