Inhibition of synaptically evoked cortical acetylcholine release by intracortical glutamate: involvement of GABAergic neurons.
Cortical acetylcholine (ACh) has been shown to regulate diverse cognitive processes and its release can be regulated by neuromodulators that act presynaptically at cholinergic terminals. The neocortex receives dense glutamatergic input from thalamocortical and other fibres. The present study used in vivo microdialysis to examine, and pharmacologically characterize, the effect of glutamate on cortical ACh release evoked by electrical stimulation of the pedunculopontine tegmental nucleus in urethane-anaesthetized rats. All drugs were administered locally within the cortex by reverse dialysis. Application of glutamate had no detectable effect on spontaneous ACh release but reduced evoked cortical ACh efflux in a concentration-dependent manner. This effect was mimicked by the glutamate transporter blocker L-trans-pyrrolidine-2,4-dicarboxylic acid, as well as by the ionotropic glutamate receptor agonists N-methyl-D-aspartic acid and alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid, and was blocked by the ionotropic glutamate receptor antagonists 6,7-dinitroquinoxaline-2,3-dione and (+/-)-3-(2-carboxypiperazin-4yl)-propyl-1-phosphonic acid. Glutamate application also increased extracellular adenosine levels but the simultaneous delivery of the broad-spectrum adenosine receptor antagonist caffeine failed to affect the inhibitory action of glutamate on evoked ACh release. However, the effect of glutamate was fully blocked by simultaneous delivery of the GABAA receptor antagonist bicuculline and partially blocked by the GABAB receptor antagonist phaclofen. These results suggest that ionotropic glutamate receptor activation by glutamate inhibits evoked cortical ACh release via an indirect pathway involving GABAergic neurons in the cortex.
Materi
L M
LM
Department of Anatomy and Neurobiology, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia B3H-4H7, Canada.
Semba
K
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D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D020532:Basal Nucleus of Meynert / Q000187:drug effects* / Q000378:metabolism; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D002799:Cholinergic Fibers / Q000187:drug effects* / Q000378:metabolism; D004558:Electric Stimulation; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018755:GABA Agonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D009434:Neural Pathways / Q000166:cytology / Q000502:physiology; D017729:Presynaptic Terminals / Q000187:drug effects* / Q000378:metabolism; D058906:Purinergic P1 Receptor Agonists; D051381:Rats; D017208:Rats, Wistar; D018079:Receptors, GABA / Q000187:drug effects / Q000378:metabolism; D018047:Receptors, Purinergic P1 / Q000378:metabolism; D013681:Tegmentum Mesencephali / Q000166:cytology / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D018755:GABA Agonists; D018756:GABA Antagonists; D058906:Purinergic P1 Receptor Agonists; D018079:Receptors, GABA; D018047:Receptors, Purinergic P1; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D000109:Acetylcholine