Basal forebrain glutamatergic modulation of cortical acetylcholine release.
The mediation of cortical ACh release by basal forebrain glutamate receptors was studied in awake rats fitted with microdialysis probes in medial prefrontal cortex and ipsilateral basal forebrain. Repeated presentation of a stimulus consisting of exposure to darkness with the opportunity to consume a sweetened cereal resulted in a transient increase in cortical ACh efflux. This stimulated release was dependent on basal forebrain glutamate receptor activity as intrabasalis perfusion with the ionotropic glutamate receptor antagonist kynurenate (1.0 mM) markedly attenuated darkness/cereal-induced ACh release. Activation of AMPA/kainate receptors by intrabasalis perfusion of kainate (100 microM) was sufficient to increase cortical ACh efflux even under basal (nonstimulated) conditions. This effect of kainate was blocked by coperfusion with the antagonist DNQX (0.1-5.0 mM). Stimulation of NMDA receptors with intrabasalis perfusion of NMDA (50 or 200 microM) did not increase basal cortical ACh efflux. However, perfusion of NMDA in rats following exposure to the darkness/cereal stimulus resulted in a potentiation of both the magnitude and duration of stimulated cortical ACh efflux. Moreover, intrabasalis perfusion of the higher dose of NMDA resulted in a rapid increase in cortical ACh efflux even before presentation of the darkness/cereal stimulus, suggesting an anticipatory change in the excitability of basal forebrain cholinergic neurons. These data demonstrate that basal forebrain glutamate receptors contribute to the stimulation of cortical ACh efflux in response to behavioral stimuli. The specific roles of basal forebrain glutamate receptor subtypes in mediating cortical ACh release differ and depend on the level of activity of basal forebrain cholinergic neurons.
Fadel
J
J
Department of Psychology, The Ohio State University, Columbus, Ohio 43210, USA.
Sarter
M
M
Bruno
J P
JP
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D004777:Environment; D005502:Food; D018698:Glutamic Acid / Q000502:physiology*; D008297:Male; D017551:Microdialysis; D010477:Perfusion; D016548:Prosencephalon / Q000502:physiology*; D051381:Rats; D011916:Rats, Inbred F344; D018091:Receptors, AMPA / Q000819:agonists / Q000378:metabolism; D018092:Kainic Acid Receptors / Q000378:metabolism; D009435:Synaptic Transmission / Q000502:physiology
D000109:Acetylcholine; D018698:Glutamic Acid; D018091:Receptors, AMPA; D018092:Kainic Acid Receptors