Possible mechanisms of enkephalin action on hippocampal CA1 pyramidal neurons.

(1) Intracellular and extracellular recordings were made from CA1 pyramidal neurons in an in vitro rat hippocampal slice preparation, while [D-Ala2, D-Leu5]enkephalin (DADL) was applied by perfusion at a known concentration (1 to 5 X 10-7 M), in a small droplet, or by iontophoresis into the cellular and dendritic layers of the slice. The effects of DADL on synaptic potentials and membrane properties were studied in an effort to determine the mechanisms underlying its epileptogenic action in the hippocampus. (2) DADL increased the size and often the duration of excitatory postsynaptic potentials (EPSPs) generated on either the apical or basal dendrites; this resulted in an increased discharge probability for a constant orthodromic stimulus. Extracellular field potential recordings showed a larger population spike for a given size field EPSP. These effects of DADL could be reversed substantially by perfusion with naloxone (1 to 5 X 10-7 M) and appeared qualitatively different from the epileptiform actions of penicillin. (3) DADL did not appear to increase the intrinsic excitability of the soma membrane, since membrane potential, input resistance, spike threshold, and antidromic field potentials all were unchanged. In addition, the shape of the membrane charging curve during hyperpolarizing current injection was not changed noticeably by DADL. (4) At the concentrations tested, DADL did not attenuate recurrent inhibition in the CA1 region, as evaluated by comparing in the absence and presence of DADL: (a) antidromically evoked recurrent inhibitory postsynaptic potentials (IPSPs) and their dependence of membrane potential, (b) the reduction of a synaptically driven population spike by a prior antidromic volley, (c) iontophoretic GABA (gamma-aminobutyric acid) responses. Similarly, IPSPs evoked by orthodromic stimulation appeared either unaffected or occasionally enhanced by DADL. (5) By iontophoretic mapping, it was shown that the DADL-sensitive sites are limited to stratum oriens and stratum pyramidale. Local application of DADL into stratum radiatum was relatively ineffective in enhancing the efficacy of synapses located in this region. (6) The dendritic input-output relationship between the presynaptic fiber volley and the field EPSP was not changed by DADL. This finding and the results of the iontophoretic mapping experiments suggest that increased excitatory transmitter release was not involved. (7) The data are consistent with the proposal that DADL selectively attenuates a dendritic IPSP which is virtually invisible to the soma, although the possibility cannot be ruled out that DADL may, in addition, act to enhance the responsiveness of pyramidal dendritic membrane to excitatory synaptic activation.