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George B. Richerson Associate
Professor of Neurology and
Cellular & Molecular Physiology -
B.S. 1980 Iowa State University -
M.D., Ph.D. 1987 University
of Iowa
Role of serotonergic neurons in
pH homeostasis. Serotonergic neurons within the
medulla and midbrain are highly chemosensitive to changes in pH and CO2. We have
proposed that these neurons are central chemoreceptors, and that they initiate
a homeostatic response to changes in blood CO2, including changes in respiratory
and cardiovascular output, cerebral blood flow and level of arousal. Some of these
neurons are located immediately adjacent to large blood vessels, where they can
"taste" the CO2 of the blood. They possess a novel calcium-activated cation current
that is strongly modulated by changes in pH between 7.0 and 7.6. We are using
a combination of electrophysiology, immunohistochemistry and cell biological techniques
to define the basic mechanisms of chemosensitivity in these neurons, and how their
dysfunction can lead to diseases such as SIDS, sleep apnea and panic disorder.
Nonvesicular GABA release via reversal of the GABA transporter. GABA
can still be released from neurons after vesicular fusion is blocked with tetanus
toxin or by removing extracellular calcium. This "nonvesicular" GABA release can
be induced by surprisingly small increases in membrane potential, and by anticonvulsants
that increase cytosolic [GABA]. We have proposed that this form of GABA release
complements vesicular GABA release, and acts as a fail-safe negative feedback
system during high frequency firing. We are examining the role that this form
of release, and GABA transporters, play in seizures. Recent
publications: Richerson,
G.B. Serotonergic
neurons as carbon dioxide sensors that maintain pH homeostasis. Nature Reviews
Neuroscience, 5:449-461, 2004. Severson,
C.A., W. Wang, V.A. Pieribone, C.I. Dohle & G.B. Richerson. Midbrain
serotonergic neurons are central pH chemoreceptors. Nature Neurosci 6(11):1139-1140,
2003. Richerson,
G.B. & Y. Wu. The
dynamic equilibrium of neurotransmitter transporters: Not just for reuptake anymore.
J Neurophysiol 90:1363-1374, 2003. Bradley,
S Risso, V. A. Pieribone, W. Wang, C.A. Severson, R. A. Jacobs & G. B. Richerson.
Chemosensitive
serotonergic neurons are intimately associated with large arteries of the ventral
medulla. Nature Neurosci 5(5): 401-402, 2002.
Wang, W., S. Risso
Bradley & G.B. Richerson. Quantification
of the response of rat medullary raphe neurones to independent changes in pHo
and PCO2. J Physiol (Lond) 540(3): 951-970, 2002.
Wang W, Tiwari
JK, Bradley SR, Zaykin RV, Richerson GB. Acidosis-stimulated
neurons of the medullary raphe are serotonergic. J Neurophysiol. 2001 May;85(5):2224-35.
Wu Y, Wang W, Richerson GB. GABA
transaminase inhibition induces spontaneous and enhances depolarization-evoked
GABA efflux via reversal of the GABA transporter. J Neurosci. 2001 Apr 15;21(8):2630-9.
george.richerson@yale.edu http://info.med.yale.edu/neurol/Richerson/Welcome.htm | |