ACTIVITY-DEPENDENT RESPONSE DEPRESSION IN RAT HIPPOCAMPAL CA1 PYRAMIDAL
NEURONS IN VITRO.
Borde, Michel, Jean Ren[acute]e Cazalets and Washington Bu[tilde]no.
Instituto Cajal, CSIC, Avenida Doctor Arce 37, E-28002 Madrid, SPAIN, and
NBM, CNRS, chemin Joseph Aiguier, BP 71, 13402-Marseille, France.
APStracts 2:0165N, 1995.
SUMMARY AND CONCLUSIONS
1) A gradual and prolonged decrease of the response -termed here "depression"-
evoked by repeated activation with transmembrane current stimuli was analyzed
in rat CA1 hippocampal pyramidal cells under single electrode current-clamp
using the in vitro slice technique. 2) Depression was induced by 2s duration
0.3-0.7nA current pulses presented as a sequence of 12 stimuli at 3-60s
intervals. Sinusoidal currents (0.5 to 1.0nA) at 5Hz or 200ms pulses repeated
at 0.3-0.5/s, which may be more natural stimulations, also induced depression.
3) Depression outlasted stimulation up to 170s in all cells tested. The
initial high rate spike burst changed little (<20%), whereas the lower rate
adapted response decreased markedly (>40%). Thus, neurons increased their rate
of adaptation. The after-hyperpolarizations following pulse evoked responses
increased in duration and amplitude with depression. There were input
resistance (R in ) reductions at depolarized membrane potentials and during
pulses. However, R in reductions were considerably smaller or altogether
absent late during interpulse intervals. Subthreshold current stimuli were
ineffective, indicating that spike activity was necessary to elicit
depression. 4) Depression was: (a) insensitive to the toxin _-Aga-IVA (0.5
[mu]M) which blocked synaptic transmission, revealing a key involvement of
intrinsic properties and little if any synaptic participation; (b) insensitive
to 4-aminopyrydine (2.00-4.00mM) which greatly enhanced excitatory and
inhibitory synaptic efficacy, again suggesting little synaptic involvement and
a principal postsynaptic participation, and no participation of the K + -
mediated currents I A and I D ; (c) abolished by carbamalcholine (5.0-
20.0[mu]M) -an effect blocked by atropine (1.0-10.0[mu]M)-, and reduced by Ca
2+ -free solutions, and by intracellular injection of the Ca 2+ chelator
BAPTA, suggesting that Ca 2+ -dependent K + -mediated currents are key
factors, with a less important participation of the K + -mediated I M current.
5) We conclude that depression was due to activity-dependent modifications in
intrinsic properties, with little if any synaptic participation. Depression
may be functionally significant because it was induced by potentially natural
stimulations. A model is proposed which accounts for the main traits of
depression. In the model depression was induced by a gradual decline of the
speed at which Ca 2+ was buffered intracellularly; an increase in the I K(Ca)S
activation rate constant also simulated depression.
Received 29 December 1994; accepted in final form 22 May 1995.
APS Manuscript Number J827-4.
Article publication pending J. Neurophysiol.
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 8 June 1995.