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The Journal of Neuroscience, January 1, 2000, 20(1):66-75
Nicotinic Receptor Activation in Human Cerebral Cortical
Interneurons: a Mechanism for Inhibition and Disinhibition of Neuronal
Networks
Manickavasagom
Alkondon1,
Edna F. R.
Pereira1,
Howard
M.
Eisenberg2, and
Edson X.
Albuquerque1, 3
1 Departments of Pharmacology and Experimental
Therapeutics, and 2 Neurosurgery, University of Maryland
School of Medicine, Baltimore, Maryland 21201, and
3 Departamento de Farmacologia Básica e
Clínica, Instituto de Ciências Biomédicas, Centro
de Ciências da Saúde, Universidade Federal do Rio de
Janeiro, Rio de Janeiro, RJ 21944, Brazil
Cholinergic control of the activity of human cerebral cortical
circuits has long been thought to be accounted for by the interaction of acetylcholine (ACh) with muscarinic receptors. Here we report the
discovery of functional nicotinic receptors (nAChRs) in interneurons of
the human cerebral cortex and discuss the physiological and clinical
implications of these findings. The whole-cell mode of the patch-clamp
technique was used to record responses triggered by U-tube application
of the nonselective agonist ACh and of the  7-nAChR-selective agonist
choline to interneurons visualized by means of infrared-assisted
videomicroscopy in slices of the human cerebral cortex. Choline induced
rapidly desensitizing whole-cell currents that, being sensitive to
blockade by methyllycaconitine (MLA; 50 nM), were most
likely subserved by an 7-like nAChR. In contrast, ACh evoked slowly
decaying whole-cell currents that, being sensitive to blockade by
dihydro- -erythroidine (DHE; 10 µM), were most
likely subserved by an 42-like nAChR. Application of ACh (but not
choline) to the slices also triggered GABAergic postsynaptic currents
(PSCs). Evidence is provided that ACh-evoked PSCs are the result of
activation of 42-like nAChRs present in preterminal axon segments
and/or in presynaptic terminals of interneurons. Thus, nAChRs can relay
inhibitory and/or disinhibitory signals to pyramidal neurons and
thereby modulate the activity of neuronal circuits in the human
cerebral cortex. These mechanisms, which appear to be retained across
species, can account for the involvement of nAChRs in cognitive
functions and in certain neuropathological conditions.
Key words:
acetylcholine; choline; GABA; patch-clamp; methyllycaconitine; dihydro--erythroidine
Copyright © 2000 Society for Neuroscience 0270-6474/0/20166-10$05.00/0
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