Gordon Buchanan MD PhD
Assistant Professor of Neurology
Sleep; Arousal mechanisms; Epilepsy; Sudden Unexpected Death in Epilepsy (SUDEP); Circadian rhythms; Breathing; Serotonin; Animal models
Research efforts in my laboratory are focused on understanding basic mechanisms of sleep-wake regulation and epilepsy. We are particularly interested in regulation of normal sleep architecture, mechanisms of stimulus-induced arousal from sleep, seizure susceptibility, seizure-related mortality, ictal- and post-ictal- cardiorespiratory function, circadian regulation and effects of sleep deprivation. We are especially interested in those mechanisms involving monoaminergic signaling. A major current project is focused on understanding how serotonin neurons, as central chemoreceptors that sense alterations in CO2 levels, mediate arousal to CO2 and how these mechanisms translate to breathing regulation and stimulus-sensitivity in the period immediately following a seizure. We employ eleltroencephalographic (EEG), electromyographic (EMG), and electrocardiographic (EKG) recordings along with whole body plethysmography and activity and body temperature telemetry in live, chronically insturmented normal and transgenic mouse strains. Other techniques used in the lab include stereotactic surgery for intracranial injection of neuroactive substances and neurochemical ablation of specific neuronal subpopulations, reverse microdialysis of neuroactive substances, chemical and electrical seizure induction, intracardiac perfusion and tissue immunostaining.
Extensive Research Description
All human beings experience arousal state transitions on a daily basis. The ability to transition from wakefulness and sleep and back to wakefulness involves an intricate series of underlying regulatory mechanisms. While the reason that we sleep is not entirely clear, it is very clear that daily sleep is necessary. Being able to transition out of sleep spontaneously, or in response to a stimulus (eg. alarm clock, crying baby, smell of smoke, etc) is of vital importance to our existence. Abnormal state transitions underlie such diseases as narcolepsy and primary insomnia/hypersomnia. And derangements in the ability to arouse to certain stimuli may play a role in sudden death syndromes such as, sudden infant death syndrome (SIDS) and sudden unexpected death in epilepsy (SUDEP). Another condition in which there could be perceived to be abnormal state transitions is epilepsy. Patients with epilepsy function in a seemingly normal manner the majority of the time, but periodically experience a seizure due to their underlying predisposition. Understanding mechanisms by which normal transitions between vigilance states and transitions the normal pre-ictal state to seizures occur in important to understanding and correcting abnormalities in the abovementioned disease states.