Cerebral Cortex, Vol 7, 502-509, Copyright © 1997 by Oxford University Press
AC Tang, AM Bartels and TJ Sejnowski
Neocortical neurons in vivo are spontaneously active and intracellular
recordings have revealed strongly fluctuating membrane potentials arising
from the irregular arrival of excitatory and inhibitory synaptic
potentials. In addition to these rapid fluctuations, more slowly varying
influences from diffuse activation of neuromodulatory systems alter the
excitability of cortical neurons by modulating a variety of potassium
conductances. In particular, acetylcholine, which effects learning and
memory, reduces the slow alterhyperpolarization, which contributes to spike
frequency adaptation. We used whole-cell patch-clamp recordings of
pyramidal neurons in neocortical slices and computational simulations to
show, first, that when fluctuating inputs were added to a constant current
pulse, spike frequency adaptation was reduced as the amplitude of the
fluctuations was increased. High- frequency, high-amplitude fluctuating
inputs that resembled in vivo conditions exhibited only weak spike
frequency adaptation. Second, bath application of carbachol, a cholinergic
agonist, significantly increased the firing rate in response to a
fluctuating input but minimally displaced the spike times by < 3 ms,
comparable to the spike jitter observed when a visual stimulus is repeated
under in vivo conditions. These results suggest that cholinergic modulation
may preserve information encoded in precise spike timing, but not in
interspike intervals, and that cholinergic mechanisms other than those
involving adaptation may contribute significantly to cholinergic modulation
of learning and memory.
ARTICLES
Effects of cholinergic modulation on responses of neocortical neurons to fluctuating input
Howard Hughes Medical Institute, Computational Neurobiology Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
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