Removal of GABAergic inhibition in the mediodorsal nucleus of the rat thalamus leads to increases in heart rate and blood pressure.
The mediodorsal nucleus of the thalamus (MD) has connections with central autonomic centers involved in cardiovascular control and undergoes severe degeneration in fatal familial insomnia, a human disease characterized by progressive dysautonomia. Microinjections of the GABAA antagonist bicuculline methiodide (BMI) into the medial and central portion of the MD lead to significant, dose-dependent increases in both heart rate and blood pressure. Similar injections into surrounding regions elicited little to no change. The data suggest that the medial and central portion of the MD plays a role in central cardiovascular regulation. Neurons of the MD may be under tonic GABAergic inhibition, and disruption of circuits at this level may underlie dysautonomia in many neurological diseases.
Stotz-Potter
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Department of Neurology, Mayo Clinic, Rochester, MN 55905, USA.
Benarroch
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D000818:Animals; D001342:Autonomic Nervous System Diseases / Q000235:genetics / Q000503:physiopathology*; D001640:Bicuculline / Q000031:analogs & derivatives* / Q000494:pharmacology; D001794:Blood Pressure / Q000502:physiology*; D018756:GABA Antagonists / Q000494:pharmacology*; D058787:GABA-A Receptor Antagonists; D006339:Heart Rate / Q000502:physiology*; D006801:Humans; D008845:Microinjections; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000502:physiology; D007319:Sleep Initiation and Maintenance Disorders / Q000235:genetics / Q000503:physiopathology*; D013787:Thalamic Nuclei / Q000187:drug effects / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D018756:GABA Antagonists; D058787:GABA-A Receptor Antagonists; D011963:Receptors, GABA-A; C017069:bicuculline methiodide; D005680:gamma-Aminobutyric Acid; D001640:Bicuculline