Long Term Modulation of Intrinsic Membrane Properties of Hippocampal Neurons
We studied the mechanisms of action of acetylcholine (ACh) and dopamine (DA) on hippocampal CA1 pyramidal cells of the in vitro slice preparation. ACh caused an initial hyperpolarization in half the cells studied which was eliminated when synaptic transmission was blocked and was therefore presynaptic in origin. Muscarinic excitation was evoked in all neurons and consisted of slow depolarization and a voltage-sensitive increase in membrane resis-tance (RN) which resulted from antagonism of a voltage-dependent K+ conductance. RN increases lasted hours after a single ACh application and concomitant changes in cell firing mode from single sp+kes to burst generation occurred. This long term effect was Ca dependent. DA application resulted in spontaneous hyperpolarization and an increase in the amplitude and duration of the afterhyperpolarizations (AHPs) which normally follow repetitive spiking. These effects were long-lasting and associated with up to a 22% decrease in RN. DA-induced hyperpolarizations persisted in cells impaled with C1− -containing electrodes and had a reversal potential of about −87 mV, findings consistent with an increased K+ conductance. Mn2+ blocked the spontaneous or evoked hyperpolarizations produced by DA (1 μM), ho ver Wger volume DA applications were effective even in low Ca2+, Mn2+ -containing solutions. Intracellular EGTA blocked all DA actions. DA effects were mimicked by DA agonists and by intra- or extracellular application of cAMP, and blocked by DA antagonists. We conclie that DA actions are medied by effect on intracellular [Ca2+] which in turn modulates a Ca2+ -activated K+ conductance. The long term nature of these actions may relate to receptor coupled increases in cAMP.
ACh and DA are neuromodulators which produce long term alterations is intrinsic call properties and would be expected to effectively alter the influences of other afferent systems. The implications for learning and memory are discussed.
KeywordsCurrent Pulse Pyramidal Cell Hippocampal Pyramidal Neuron Hippocampal Pyramidal Cell Burst Generation
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