Hengen KB, Behan M, Carey HV, Jones MV, Johnson SM Hibernation induces pentobarbital insensitivity in medulla but not cortex. [JOURNAL ARTICLE] Am J Physiol Regul Integr Comp Physiol 2009 Aug 12.
The 13-lined ground squirrel (Spermophilus tridecemlineatus), a hibernating species, is a natural model of physiological adaption to an extreme environment. During torpor, body temperature drops to 0-4 degrees C and the cortex is electrically silent, yet the brainstem continues to regulate cardiorespiratory function. The mechanisms underlying selective inhibition in the brain during torpor are not known. To test whether altered GABAergic function is involved in regional and seasonal differences in neuronal activity, cortical and medullary slices from summer active (SA) and interbout aroused (IBA) squirrels were placed in a standard in vitro recording chamber. Silicon multichannel electrodes were placed in cortex, ventral respiratory column (VRC), and nucleus tractus solitarius (NTS) to record spontaneous neuronal activity. In slices from IBA squirrels, bath-applied pentobarbital (300 microM) nearly abolished cortical neuronal activity, but VRC and NTS neuronal activity was unaltered. In contrast, pentobarbital (300 microM) nearly abolished all spontaneous cortical, VRC, and NTS neuronal activity in slices from SA squirrels. Muscimol (20 microM; GABAA receptor agonist) abolished all neuronal activity in cortical and medullary slices from both IBA and SA squirrels, thereby demonstrating the presence of functional GABAA receptors. Pretreatment of cortical slices from IBA squirrels with bicuculline (100 microM; GABAA receptor antagonist) blocked pentobarbital-dependent inhibition of spontaneous neuronal activity. We hypothesize that GABAA receptors undergo a seasonal modification in subunit composition such that cardiorespiratory neurons are uniquely unaffected by surges of an endogenous allosteric positive modulator. Key words: GABA receptors, VRG, NTS, respiratory control.
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