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Amy B. MacDermott, Ph.D.
Professor of Physiology and Cellular Biophysics and Neuroscience
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Research
Summary
Regulation of synaptic transmission in the superficial dorsal horn.
Nociceptors carrying pain input from the periphery terminate in the superficial aspect of the spinal cord dorsal horn. The input travels along primary afferent axons of the dorsal root ganglia and its excitatory signal is transmitted by the release of glutamate, substance P and possibly ATP onto target dorsal horn neurons. In this laboratory, we use electrophysiological, optical, and immunocytochemical techniques to study the regulation of synaptic transmission in the superficial dorsal horn. We have been investigating the specific role of glutamate, substance P and ATP in synaptic transmission, synaptic plasticity, and development of synapses in the spinal cord dorsal horn.
Current Research
1. Nociceptors and glutamate receptors
There are multiple subpopulations of nociceptors with cells bodies in the dorsal root ganglion (DRG). They can be grouped by sensory modality, by intracellular markers such as peptides, or by surface markers such as those developed and characterized by Dodd and Jessell (1985). We will use immunocytochemistry to identify DRG nociceptor subpopulations. We will test individual populations of nociceptors for expression of several nociceptive properties including low and high threshold heat and capsaicin sensitivity, using Ca2+ imaging and electrophysiology to measure responses. Using the spinal cord slice preparation with attached dorsal root and co-cultures of identified nociceptors and dorsal horn neurons, we will investigate where AMPA and kainate receptors are expressed central to the DRG and specifically whether they are expressed on the nociceptor nerve terminals. We will determine the impact of receptor activation on glutamate release from the primary afferent terminals. National Institute of Neurological Disorders and Stroke (7/2000-6/2004).
2. Non-NMDA receptors and the dorsal horn
We plan to use postnatal rat spinal cord slices to study the role of pre and postsynaptic AMPA receptors in regulating synaptic transmission in the spinal cord dorsal horn. Using electrophysiology, Ca2+ and general fluorescent imaging, and immunocytochemistry, we will clarify the location and function of the Ca2+ permeable non-NMDA receptors in the dorsal horn. We will use co-cultures of nociceptors and dorsal horn neurons grown on microislands to determine the rules for sorting of Ca2+ permeable AMPA receptors and NMDA receptors at individual synaptic sites and how that impacts on the activity dependence of each synapse studied. In addition to developing our understanding of regulation of nociceptive information transmission in the dorsal horn, these studies may also contribute to the development of new drugs for alleviating pain that are targeted to the unexplored cell specific AMPA receptors we propose to study. National Institute of Neurological Disorders and Stroke (4/1992-6/2004).
http://www.sklad.cumc.columbia.edu/neuroscienceinitiatives/index.php?page=28&bio=122
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Selected Publications:
1. Labrakakis C, MacDermott AB. (2003) Neurokinin receptor 1-expressing spinal cord neurons in lamina I and III/IV of postnatal rats receive inputs from capsaicin sensitive fibers. Neurosci Lett.
352(2):121-4.
2. Labrakakis C, Tong CK, Weissman T, Torsney C, MacDermott AB. (2003) Localization and function of ATP and GABAA receptors expressed by nociceptors and other postnatal sensory neurons in rat. J Physiol.
549(Pt 1):131-42.
3. Lee CJ, Bardoni R, Tong CK, Engelman HS, Joseph DJ, Magherini PC, MacDermott AB. (2002) Functional expression of AMPA receptors on central terminals of rat dorsal root ganglion neurons and presynaptic inhibition of glutamate release. Neuron.
35(1):135-46.
4. MacDermott AB. (2001) Glutamate and GABA: a painful combination. Neuron.
32(3):376-8.
5. Lee CJ, Kong H, Manzini MC, Albuquerque C, Chao MV, MacDermott AB. (2001) Kainate receptors expressed by a subpopulation of developing nociceptors rapidly switch from high to low Ca2+ permeability. J Neurosci.
21(13):4572-81.
6. Labrakakis C, Gerstner E, MacDermott AB. (2000) Adenosine triphosphate-evoked currents in cultured dorsal root ganglion neurons obtained from rat embryos: desensitization kinetics and modulation of glutamate release. Neuroscience.
101(4):1117-26.
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