Assistant Professor
E-Mail:
jamespeters@vetmed.wsu.edu
Office: VBRB rm. 435
Phone: (509) 335-0517
Our laboratory investigates the peripheral and central neurocircuitry
that provides critical controls of food intake and energy homeostasis.
In the caudal brainstem the nucleus of the solitary tract (NTS)
integrates vagal afferent information arriving from across visceral
organ systems to initiate homeostatic reflex pathways, including those
essential for the controls of food intake. Centrally, vagal afferents
converge to form the solitary tract (ST) and contact second order NTS
neurons via strong excitatory glutamatergic synapses. A major focus of
ongoing work is to understand the pre- and post-synaptic controls of
this first central synapse. We use a combination of in vivo and in vitro
experimental approaches, including; primary culture, patch-clamp
electrophysiology, and fluorescent calcium imaging.
Recently we have been actively pursuing the contribution of
thermosensitive TRP channels in the control neuronal activation and
central glutamate release. At central ST-NTS synapses action-potential
invasion releases multiple glutamate vesicles that are precisely
synchronized with terminal depolarization. This robust 'synchronous'
form of glutamate release is thought to be the predominate mode of fast
neurotransmission at the ST-NTS synapse. Recently, however we identified
a novel form of activity-dependent 'asynchronous' glutamate release from
a subgroup of vagal afferents. In contrast with synchronous release,
this additional form of neurotransmission is only loosely coordinated
with depolarization and continues for many seconds, effectively doubling
the synaptic strength. As a result of this additional charge transfer
the postsynaptic excitatory period is significantly extended,
dramatically transforming the nature of information transfer. ST
afferents are divided into myelinated (A-fiber) and unmyelinated
(C-fiber) phenotypes with physiologically distinct functions. One
important difference between subtypes is that C-fiber afferents express
the calcium permeable non-selective ion channel 'transient receptor
potential vanilloid type 1' (TRPV1). We find that all afferents with
activity-dependent asynchronous release are also activated by the TRPV1
agonist capsaicin. Further, antagonism of TRPV1 activity selectively
reduced the asynchronous release profile with no effect on synchronous.
An attenuated asynchronous release process persists in TRPV1 KO mice and
is reduced by ruthenium red. Together these findings suggest membrane
depolarization endogenously activates TRPV1, and other
thermosensitive-TRP
channels, expressed in the central terminals of vagal afferents
resulting in asynchronous glutamate release. Delineation of the
endogenous cellular mechanisms underlying TRP channel activation and
their role in the control of food intake are the primary ongoing
projects in the lab.
Biographical Information
James Peters earned his bachelor’s of science (B.S.) in biology from
Eastern Oregon University (La Grande, OR) in 2001 and his Ph.D. in
Neuroscience from Washington State University (Pullman, WA) in 2005. His
graduate thesis advisors were Dr. Robert Ritter and Dr. Steven Simasko.
During his graduate training he was privileged to receive an ARCS
Foundation Fellowship and Poncin Foundation Fellowship to help support
his studies.
Following graduate work he did a postdoctoral fellowship at Oregon
Health and Science University (OHSU) in Portland, OR with Dr. Michael C.
Andresen. This work was supported by an individual postdoctoral
fellowship through the NIH. Returning to Pullman he assumed a faculty
position at Washington State University as a Research Assistant
Professor from 2010-2012; and in 2012 began as an Assistant professor in
IPN and the Neuroscience Graduate Faculty at Washington State
University.
Selected Publications
1. Kinch DC,
Peters JH, and Simasko SM (2012)
Comparative pharmacology of cholecystokinin induced activation of
cultured vagal afferent neurons from rats and mice. PLoS One
2.
Peters JH, McDougall SJ, Fawley JA, and Andresen MC
(2011) TRPV1 marks synaptic segregation of multiple convergent afferents
at the rat medial solitary tract nucleus. PLoS One 6: 25015.PMID:
21949835
3. Fawley JA,
Peters JH, and Andresen MC (2011) GABAB-mediated
inhibition of multiple modes of glutamate release in the nucleus of the
solitary tract. Journal of Neurophysiology 106:1833-40. PMID: 21734101
4. Shoudai K,
Peters JH, McDougall SJ, and Andresen MC
(2010) Thermally active TRPV1 tonically drives central spontaneous
glutamate release. J Neuroscience 30: 14470-5. PMID: 20980604
5.
Peters JH, McDougall SJ, Fawley JA, Smith SM, and
Andresen MC (2010) Primary afferent activation of thermosensitive TRPV1
triggers asynchronous glutamate release at central neurons. Neuron
65:657-69. PMID: 20223201
6. McDougall SJ,
Peters JH, and Andresen MC (2009)
Convergence of cranial visceral afferents within the solitary tract
nucleus. J Neuroscience 29:12886-95. PMID: 19828803
7.
Peters JH, McDougall SJ, Kellett DO, Jordan D,
Llewellyn-Smith IJ, and Andresen MC (2008) Oxytocin enhances cranial
visceral afferent synaptic transmission to the solitary tract nucleus. J
Neuroscience 28:11731-40. *See comment in J Neuroscience 2009,
29:4687-9. PMID: 18987209
8. Andresen MC and
Peters JH (2008) Comparison of
baroreceptive to other afferent synaptic transmission to the solitary
tract nucleus. Am J Physiol Heart Circ Physiol. 295:H2032-42. PMID:
18790834 PMCID: PMC2614577
