Enhancement of synaptic transmission by 4‐aminopyridine in hippocampal slices of the rat.

Abstract

The effects of 4-aminopyridine (4-AP) on neurotransmission in hippocampal slices of the rat were studied in vitro. Extracellular recordings of field potentials and intracellular recordings of excitatory and inhibitory postsynaptic potentials, action potentials and TTX[tetrodotoxin]-resistant spikes were obtained from the somatic and dendritic fields of CA1 hippocampal neurons. Constant perfusion with, or bolus injection of, 4-AP in micromolar concentrations resulted in substantial and persistent enhancement of the amplitude of synaptic field potentials and population spikes, with no alteration of the afferent input. Somatic positive waves (p-waves) were increased after local micro-application of 4-AP. Intracellular recordings revealed an increase in the amplitude of e.p.s.p. [excitatory postsynaptic potential] and i.p.s.p. [inhibitory postsynaptic potential]. I.p.s.p. were prolonged by 4-AP. The pyramidal cells were, after an initial hyperpolarization, depolarized by up to 10 mV during exposure to 4-AP. The membrane conductance was not consistently changed. Spontaneous shifts of the membrane potential were described as giant e.p.s.p. and i.p.s.p. Spontaneous i.p.s.p. were increased in frequency and amplitude. Paired-pulse facilitation of e.p.s.p. was reduced by 4-AP, suggesting a presynaptic modulation of transmitter output. 4-AP evidently enhances transmitter release at both excitatory and inhibitory synapses in the hippocampus.