Purinergic inhibition of GABA and glutamate release in the thalamus: implications for thalamic network activity.
Adenosine is a CNS depressant with both pre- and postsynaptic actions. Presynaptically, adenosine decreases neurotransmitter release in the hippocampus but only at excitatory terminals. In the thalamus, however, we show that, in addition to its actions at excitatory synapses, adenosine strongly suppresses monosynaptic inhibitory currents both in relay cells of the thalamic ventrobasal complex (VB) and in inhibitory neurons of the nucleus reticularis thalami (nRt). A concomitant increase in transmission failures and results coefficient of variation analysis are both consistent with a presynaptic mechanism. Pharmacological manipulations support an A1 receptor-mediated process. Slow thalamic oscillations induced in vitro by extracellular stimulation and recorded with extracellular multiunit electrodes in VB and nRt are dampened by adenosine without affecting their periodicity. We conclude that adenosine can presynaptically down-regulate inhibitory postsynaptic responses in thalamus and exert robust antioscillatory effects, likely by synergistic depression of both excitatory and inhibitory neurotransmitter release.
Ulrich
D
D
Department of Neurology and Neurological Sciences, Stanford University School of Medicine, California 94305, USA.
Huguenard
J R
JR
D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology*; D000818:Animals; D001640:Bicuculline / Q000031:analogs & derivatives / Q000494:pharmacology; D004553:Electric Conductivity; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D005260:Female; D018756:GABA Antagonists / Q000494:pharmacology*; D018698:Glutamic Acid / Q000378:metabolism*; D008297:Male; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D018047:Receptors, Purinergic P1 / Q000187:drug effects / Q000502:physiology; D013569:Synapses / Q000187:drug effects / Q000502:physiology; D013788:Thalamus / Q000187:drug effects / Q000502:physiology*; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D011810:Quinoxalines; D018047:Receptors, Purinergic P1; C053907:8-cyclopentyl-1,3-dimethylxanthine; D018698:Glutamic Acid; C017069:bicuculline methiodide; C048599:N(6)-cyclopentyladenosine; D005680:gamma-Aminobutyric Acid; C056723:FG 9041; D013806:Theophylline; D000241:Adenosine; D001640:Bicuculline