Cholinergic excitation of mammalian hippocampal pyramidal cells

Responses of CA1 pyramidal neurons to ACh were recorded with intracellular microelectrodes utilizing the in vitro guinea pig hippocampal slice preparation. ACh was delivered by drop or iontophoretic application to stratum oriens or stratum radiatum. Threshold dose for drop application was 1 mM. An initial hyperpolarization of 3.1 +/- 1.8 (S.D.) mV associated with a decrease in membrane input resistance (RN) of 21 +/- 9% (S.D.) occurred in about half the cells. This result is consistent with a presynaptic action of ACh mediated through excitation of inhibitory interneurons. This interpretation was supported by recordings of cholinergic excitatory responses from presumed interneurons, and repetitive spontaneous IPSPs from pyramidal neurons during the hyperpolarization. ACh evoked a slow depolarization (14.3 +/- 10.8 (S.D.) mV) accompanied by a peak increase in apparent input resistance (Ra) of about 60% in the majority of cells. Large increases in spike frequency were associated with these events but action potential shape was unchanged. Plots of Ra versus membrane potential following ACh application revealed that Ra increases were proportionately higher at depolarized membrane potential levels (less than or equal to -70 mV) in some neurons. In these cells Ra was increased significantly at -60 mV (28%), but only 6% at -75 mV. These results are consistent with the conclusion that ACh reduces a voltage-dependent gK, distinct from delayed rectification. ACh also induced a non-voltage-dependent increase in Ra in some cells. ACh-evoked changes in Ra were long-lasting and gave rise to alterations in firing mode, with development of burst generation. ACh also transiently blocked after hyperpolarizations which followed spike trains in pyramidal neurons and presumed interneurons, an action which may be related to effects on a Ca2+-activated gK.