Journal of Neuroscience, Vol 1, 1022-1035, Copyright © 1981 by Society for Neuroscience
Possible mechanisms of enkephalin action on hippocampal CA1 pyramidal neurons
R Dingledine
(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.