Cardiac arrhythmias and respiratory depression are both proposed to be mechanisms that lead to SUDEP; however respiratory mechanisms have not been studied as extensively as cardiac causes. SUDEP is a major cause of death in patients with epilepsy, by some estimates accounting for up to 50% of mortality in patients with chronic refractory epilepsy. Cardiac arrhythmias and respiratory depression are both
proposed to be mechanisms that lead to SUDEP, however respiratory mechanisms have not been studied as
extensively as cardiac causes. This proposal seeks: 1) to investigate the mechanisms underlying
hypoventilation and post-ictal coma; 2) to identify biomarkers; 3) to aid forensic diagnosis, and; 4) to discover
preventive interventions to decrease SUDEP.
This project seeks to identify anatomical pathways by which cortical seizures can invade the midbrain and brainstem and cause depressed cardiorespiratory function and arousal
Dekin, MS, GB Richerson & PA Getting. Thyrotropin-releasing hormone induces rhythmic bursting in
neurons of the nucleus tractus solitarius. PMID 3925552.
Bradley, SR, VA Pieribone, W Wang, CA Severson, RA Jacobs & GB Richerson. Chemosensitive
serotonergic neurons are closely associated with large medullary arteries. PMID 11967547.
Severson, CA, W Wang, VA Pieribone, CI Dohle & GB Richerson. Midbrain serotonergic neurons are
central pH chemoreceptors. PMID 14517544.
Richerson, G.B. Serotonergic neurons as carbon dioxide sensors that maintain pH homeostasis.PMID 15152195.
Du, W., J.F. Bautista, H. Yang, A. Diez-Sampedro, S.A. You, L. Wang, P. Kotagal, H.O. Lüders, J. Shi, J.
Cui, G.B. Richerson & Q. Wang. Calcium-sensitive potassium channelopathy in human epilepsy
and paroxysmal movement disorder. PMID 15937479.
Wu, Y., W. Wang, A. Diez-Sampedro & G.B. Richerson. Hippocampal nonvesicular neurotransmission via
reversal of the GABA transporter GAT-1. PMID 18054861.
Hodges, M.R., G.J. Tattersall, M.B. Harris, S. McEvoy, D.N. Richerson, E.S. Deneris, R.L. Johnson, Z.F.
Chen & G.B. Richerson. Defects in breathing and thermoregulation in mice with near-complete
absence of central serotonin neurons PMID 18322094.
Hodges, M.R., M. Wehner, J. Aungst, J.C. Smith & G.B. Richerson. Transgenic mice lacking serotonin
neurons have severe apnea and high mortality during development. PMID 19692608.
Kinney, H.C., G.B. Richerson, S.M. Dymecki, R.A. Darnall & E.E. Nattie. The brainstem and serotonin in
the sudden infant death syndrome. PMID 19400695.
Ptak, K., T. Yamanishi, J. Aungst, L.S. Milescu, R. Zhang, G.B. Richerson & J.C. Smith. Raphé neurons
stimulate respiratory circuit activity by multiple mechanisms via endogenously released serotonin
and substance P. PMID 19321769.
Buchanan, G.F. & G.B. Richerson. Central serotonin neurons are required for arousal to CO2. PMID 20805497.
Richerson, G.B. & G.F. Buchanan. The serotonin axis: Shared mechanisms in seizures, depression, and
SUDEP. PMID 21214537.
Ray, R., A. Corcoran, R. Brust, J. C. Kim, G.B. Richerson, E.E. Nattie & S. M. Dymecki. Homeostatic
imbalance upon acute in vivo serotonergic neuron inhibition. PMID 21798952.
Richerson, G.B., G. Aston-Jones & C.B. Saper. Brainstem modulation of brain function. In: Principles of
Neural Science, Fifth edition. Edited by Kandel, E.R., J.H. Schwartz, T.M. Jessel, A.J. Hudspeth
& S.A. Siegelbaum, 2012.
Sowers, L.P., C.A. Massey, B.K. Gehlbach, M.A. Granner & G.B. Richerson. Sudden unexpected death in
epilepsy: Fatal post-ictal respiratory and arousal mechanisms. PMID: 23707877.
Corcoran, A.E., K.G. Commons, J.C. Smith, M.B. Harris & G.B. Richerson. Dual effects of 5-HT1a receptor
activation on breathing in neonatal mice. PMID 24381267.
Massey, C.A., L.P. Sowers, B.J. Dlouhy & G.B. Richerson. Mechanisms of sudden unexpected death in
epilepsy: The pathway to prevention. PMID 24752120.