The Journal of Neuroscience, March 15, 2001, 21(6):2015-2027
Acetylcholine Becomes the Major Excitatory Neurotransmitter in
the Hypothalamus In Vitro in the Absence of Glutamate
Excitation
Andrei B.
Belousov1,
Bruce F.
O'Hara2, and
Janna V.
Denisova1
1 Department of Cell and Molecular Biology, Tulane
University, New Orleans, Louisiana 70118, and 2 Department
of Biological Sciences, Stanford University, Stanford, California 94305
Glutamate and GABA are two major fast neurotransmitters
(excitatory and inhibitory, respectively) in the CNS, including the hypothalamus. They play a key role in the control of
excitation/inhibition balance and determine the activity and
excitability of neurons in many neuronal circuits. Using neuronal
cultures, whole-cell recording, Ca2+ imaging, and
Northern blots, we studied the compensatory regulation of neuronal
activity during a prolonged decrease in glutamate excitation. We report
here that after a chronic (6-17 d) blockade of ionotropic glutamate
receptors, neurons in hypothalamic cultures revealed excitatory
electrical and Ca2+ synaptic activity, which was not
elicited in the control cultures that were not subjected to
glutamate blockade. This activity was suppressed with acetylcholine
(ACh) receptor antagonists and was potentiated by eserine, an inhibitor
of acetylcholinesterase, suggesting its cholinergic nature. The
upregulation of ACh receptors and the contribution of ACh to the
control of the excitation/inhibition balance in cultures after a
prolonged decrease in glutamate activity were also demonstrated.
Enhanced ACh transmission was also found in chronically blocked
cerebellar but not cortical cultures, suggesting the region-specific
character of glutamate-ACh interactions in the brain. We believe that
in the absence of glutamate excitation in the hypothalamus in
vitro, ACh, a neurotransmitter normally exhibiting only weak
activity in the hypothalamus, becomes the major excitatory
neurotransmitter and supports the excitation/inhibition balance. The
increase in excitatory ACh transmission during a decrease in glutamate
excitation may represent a novel form of neuronal plasticity that
regulates activity and excitability of neurons during the
glutamate/GABA imbalance.
Key words:
acetylcholine; glutamate; GABA; hypothalamus; plasticity; excitation/inhibition balance
Copyright © 2001 Society for Neuroscience 0270-6474/01/2162015-13$05.00/0