Amy MacDermott, Ph.D.Professor, Physiology & Cellular Biophysics, Neuroscience
Black Building, 11th Floor
Tel +1 212-305-3889
Area of Research
Synapses & Circuits
Mechanisms underlying synaptic transmission and modulation of synaptic transmission in spinal cord dorsal horn.
The circuitry that receives and molds pain signaling in the spinal cord dorsal horn remains mostly obscure. High threshold peripheral sensory fibers transduce noxious stimuli and transmit the signals into lamina I and II of the spinal cord dorsal horn. Low threshold fibers carrying light touch sensation terminate in lamina III/IV. Within lamina I-III there are many excitatory and inhibitory interneurons while in lamina I and III but not II, there are centrally projecting neurons. Recently, we have shown that under normal conditions, high threshold fibers synaptically excite lamina I output neurons while low threshold fibers excite lamina III output neurons. However, under conditions of pharmacological disinhibition, low threshold fibers are able to drive a polysynaptic excitatory pathway onto the lamina I projection neurons. This conditions mimics spinal changes that follow peripheral nerve injury and accompanies the development of allodynia. With this in vitro model system, we are investigating the circuitry and receptors that transmit pain signals and normally prevent touch from being perceived as pain.
Daniele, C.A. and MacDermott, A.B. (2009) Low-Threshold Primary Afferent Drive onto GABAergic Interneurons in the Superficial Dorsal Horn of the Mouse, J. Neurosci. 29, 686-695.
Tong, C.K., Kaftan, E.J., and MacDermott, A.B. (2008). Functional identification of NR2 subunits contributing to NMDA receptors on substance P receptor-expressing dorsal horn neurons. Mol Pain 4, 44.
Manzini, M.C., Joseph, D.J., MacDermott, A.B., and Mason, C.A. (2007). Differential effects of AMPA receptor activation on survival and neurite integrity during neuronal development. Mol. Cell. Neurosci. 35, 328-38.
Tong, C.K., and MacDermott, A.B. (2006). Both Ca2+-permeable and -impermeable AMPA receptors contribute to primary synaptic drive onto rat dorsal horn neurons. J. Physiol. 575, 133-44.
Torsney, C., and MacDermott, A.B. (2006). Disinhibition opens the gate to pathological pain signaling in superficial neurokinin 1 receptor-expressing neurons in rat spinal cord. J. Neurosci. 26, 1833-43.
Engelman, H.S., Anderson, R.L., Daniele, C., and MacDermott, A.B. (2006). Presynaptic alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors modulate release of inhibitory amino acids in rat spinal cord dorsal horn. Neuroscience 139, 539-53.