Circadian Rhythm; Epilepsy; Serotonin; Sleep; Sleep Arousal Disorders
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.
Specialized Terms: Sleep; Arousal mechanisms; Epilepsy; Sudden Unexpected Death in Epilepsy (SUDEP); Circadian rhythms; Breathing; Serotonin; Animal models
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.
- Buchanan, G.F. Timing, sleep and respiration in health and disease. Prog Mol Biol Transl Sci. 2013, 119: 191-219.
- Buchanan, G.F. and G.B. Richerson. Central serotonin neurons are required for arousal to CO2. Proc. Natl. Acad. Aci. USA. 2010, 107(37): 16354-16359.
- Richerson, G.B. and G.F. Buchanan. The serotonin axis: Shared mechanisms in seizures, depression and SUDEP. Epilepsia. 2011, 52(Suppl 1):28-38.
- Buchanan, G.F. and G.B. Richerson. The role of the neurotransmitter serotonin in SUDEP. In Sudden unexpected death in epilepsy: a global conversation, eds. D. Chapman, B. Moss, R. Panelli, and R. Pollard, Epilepsy Australia Ltd, Camberwell, Victoria, 2011, pp. 56-57.
- Contribution of chemosensitive serotonergic neurons to interactions between the sleep-wake cycle and respiratory control Buchanan, G.F., M.R. Hodges and G.B. Richerson. Contribution of chemosensitive serotonergic neurons to interactions between the sleep-wake cycle and respiratory control. Serotonin and Sleep: Molecular, Functional and Clinical Aspects Edited by J.M. Monti, S.R. Pandi-Perumal, B.L. Jacobs and D.J. Nutt.
- Buchanan, G.F. and G.B. Richerson. Role of chemoreceptors in mediating dyspnea. Resp Physiol Neurobiol. 2009, 167(1): 9-19.
- Buchanan, G.F. and M.U. Gillette. New light on an old paradox: Site-dependent effects of carbachol on circadian rhythms. Exp. Neurol. 2005, 193: 489-496.
Ca2+/cAMP response element binding protein (CREB)-dependent activation of Per1 is required for light-induced signaling in the suprachiasmatic nucleus circadian clock
Tischkau, S.A., J.W. Mitchell, S.-H. Tyan, G.F. Buchanan and M.U. Gillette. Ca2+/cAMP response element binding protein (CREB)-dependent activation of Per1 is required for light-induced signaling in the suprachiasmatic nucleus circadian clock. J Biol Chem. 2003 Jan 10;278(2):718-23. Epub 2002 Oct 29.
- Gillette, M.U., G.F. Buchanan, L.R. Artinian, S.E. Hamiltion, N.M. Nathanson and C. Liu. Role of the M1 receptor in mediating circadian rhythms. Life Sci. 2001, 68(22-23): 2467-2472.
Pituitary adenylyl cyclase- activating peptide: a pivotal modulator of glutamatergic regulation of the suprachiasmatic circadian clock
Chen, D., G.F. Buchanan, J.M. Ding, J. Hannibal and M.U. Gillette. Pituitary adenylyl cyclase- activating peptide: a pivotal modulator of glutamatergic regulation of the suprachiasmatic circadian clock. Proc Natl Acad Sci U S A. 1999 Nov 9;96(23):13468-73.
A neuronal ryanodine receptor mediates light-induced phase delays of the circadian clock
Ding, J.M., G.F. Buchanan, S.A. Tischkau, D. Chen, L. Kuriashkina, L.E. Faiman, J.M. Alster, P.S. McPherson, K.P. Campbell and M.U. Gillette. A neuronal ryanodine receptor mediates light-induced phase delays of the circadian clock. Nature. 1998 Jul 23;394(6691):381-4.