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The Journal of Neuroscience, January 1, 2001, 21(1):75-83
Cholinergic Modulation of Excitatory Synaptic Transmission in the
CA3 Area of the Hippocampus
Kaspar E.
Vogt and
Wade G.
Regehr
Department of Neurobiology, Harvard Medical School, Boston,
Massachusetts 02115
Cholinergic innervation of the hippocampus has been implicated in
memory formation and retrieval. Here we study cholinergic modulation of
excitatory transmission in the CA3 area of the rat hippocampus. We used
a combination of optical measurements of presynaptic calcium and
electrophysiological measurements of synaptic currents to study
associational-commissural (A/C) and mossy fiber (MF) synapses in brain
slices. Direct synaptic modulation mediated by ACh receptors is only
evident at the A/C synapse, where synaptic inhibition primarily
reflects presynaptic calcium channel inhibition mediated by muscarinic
receptors. MF synapses can, however, be indirectly modulated by
muscarinic receptor activation. Muscarine elevates the firing rate of
inhibitory cells, which increases GABA release and inhibits MF synapses
by activating presynaptic GABAB receptors. Muscarine also
depolarizes dentate granule cells and elevates their rate of firing.
This leads to synaptic enhancement when combined with the use-dependent
facilitation of MF synapses. In addition we were unable to evoke an
increase in presynaptic calcium levels in MF boutons with local
application of nicotinic receptor agonists. This finding does not
support a leading hypothesis for MF modulation in which activation of
presynaptic nicotinic receptors enhances transmission directly by
elevating presynaptic calcium levels. However, indirect synaptic
modulation could arise from nicotinic excitation of inhibitory neurons.
Thus, to understand cholinergic modulation within the CA3 region, it is
necessary to take into account secondary actions on synapses arising
from other chemical messengers released by other cell types and to consider effects on firing patterns of presynaptic cells, which in turn
influence release via use-dependent synaptic plasticity.
Key words:
acetylcholine; hippocampus; associational-commissural; mossy fiber; muscarine; nicotine; presynaptic; calcium; fura-2; magnesium green
Copyright © 2001 Society for Neuroscience 0270-6474/01/21175-09$05.00/0
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