Dendritic Na+ channels amplify EPSPs in hippocampal CA1 pyramidal cells.
Lipowsky, Rupert, Thomas Gillessen, and Christian Alzheimer.
Department of Physiology, University of Munich, Pettenkoferstr. 12, D-80336
APStracts 3:0114N, 1996.
SUMMARY AND CONCLUSIONS
1. Whole-cell recordings were performed on the somata of CA1 pyramidal neurons
in the rat hippocampal slice preparation. Remote synaptic events were evoked
by electrical stimulation of Schaffer collateral/commissural fibers in outer
stratum radiatum. To isolate non-NMDA-mediated EPSPs, bath solutions contained
the NMDA receptor antagonist, D-APV (30 [mu]M), the GABA A receptor
antagonist, bicuculline (10 [mu]M), and the GABA B receptor antagonists, CGP
35348 (30 [mu]M) or, in some experiments, saclofen (100 [mu]M). 2. Local
application of TTX (0.5 - 10 [mu]M) into the proximal region of the apical
dendrite reduced the peak amplitude of somatically recorded EPSPs by 28% on
average. In contrast to dendritic TTX application, injection of TTX into the
axosomatic region of the recorded neuron reduced EPSP amplitude by only 12% on
average. 3. Spill-over of dendritically applied TTX into stratum pyramidale or
into outer stratum radiatum was ruled out experimentally: Somatic action
potentials and field EPSPs recorded near the stimulation site in outer stratum
radiatum remained unaffected by local TTX application. 4. Variations of
somatic membrane potential revealed a strong voltage dependence of EPSP
reduction after dendritic TTX application, with the effect increasing
substantially with membrane depolarization. Together with the field recordings
from stratum radiatum, this finding argues strongly against a predominantly
presynaptic site of TTX action. 5. We therefore ascribe the EPSP decrease
after local TTX application to the proximal dendrite to suppression of
dendritic Na + channels which we assume to give rise to a noninactivating
(persistent) Na + current ( I NaP ) in the subthreshold voltage range. Our
data suggest that presumed dendritic I NaP produces considerable elevation of
remote excitatory signals, thereby compensating for much of their electrotonic
attenuation. 6. The experimental findings were related to computer simulations
performed on a reduced compartmental model of the CA1 neuron. Because the
experimental evidence available so far yields only indirect clues on the
strength and distribution of I NaP , we allowed considerable variations in
these parameters. We also varied both size and location of synaptic input. 7.
The major conclusions drawn from these simulations are the following: (i)
somatic I NaP alone produces little EPSP enhancement, (ii) I NaP density at
the axon hillock/initial segement has to be at least twice the density at the
soma to produce substantial EPSP amplification, (iii) depending on the density
and distribution of dendritic I NaP , up to 80% of a remote synaptic potential
arrives at the soma (compared to only 52% in a passive dendrite), (iv)
synaptic potentials receive progressively more elevation by dendritic I NaP
the stronger they are, (v) even if restricted to the proximal segment of the
apical dendrite, I NaP also affects dendritic processing at more distal
segments, and (vi) spatial distribution rather than local density appears to
be the most important parameter determining the role of dendritic I NaP in
Received 22 January 1996; accepted in final form 21 May 1996.
APS Manuscript Number J41-6.
Article publication pending J. Neurophysiol.
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 17 June 96