Functional Organization of Spinal Somatosensory Circuits
The spinal cord plays a critical role in processing somatosensory information—touch, temperature, pain and itch. Our lab is interested in characterizing these spinal microcircuits. This knowledge is important because dysfunction of these neural circuits can lead to pathological conditions of chronic pain and itch.
Our lab uses a combination of approaches to dissect these neural circuits:
Recently, our lab has developed a novel, semi-intact somatosensory preparation that allows us to probe spinal circuits with unprecedented power (figure on left). This approach gives us, for the first time, the ability to record from the output neurons (via retrograde labeling of spinal projection neurons) while we control somatosensory input (via natural stimulation of the skin) and simultaneously manipulate activity of specific populations of spinal interneurons (via the combination of Cre alleles and optogenetics). The goal of this proposal is to use this newly developed physiological preparation to address long-standing questions in the field of somatosensation such as: How is itch distinguished from pain? How does scratching relieve itch? What mechanisms cause the abnormal amplification of pain?
Significance: Improved understanding of the neural basis of pain and itch is of clinical relevance to millions of people worldwide that suffer from clinical conditions, particularly chronic pain, that result from of maladaptive changes in neural circuitry.
Keratinocytes can modulate and directly initiate nociceptive responses.
Baumbauer KM, DeBerry JJ, Adelman PC, Miller RH, Hachisuka J, Lee KH, Ross SE, Koerber HR, Davis BM, Albers KM.
Elife. 2015 Sep 2;4.
Transcription factor PRDM8 is required for rod bipolar and type 2 OFF-cone bipolar cell survival and amacrine subtype identity.
Jung CC, Atan D, Ng D, Ploder L, Ross SE, Klein M, Birch DG, Diez E, McInnes RR.
Proc Natl Acad Sci U S A. 2015 Jun 9;112(23):E3010-9.
Identification of spinal circuits transmitting and gating mechanical pain.
Duan B, Cheng L, Bourane S, Britz O, Padilla C, Garcia-Campmany L, Krashes M, Knowlton W, Velasquez T, Ren X, Ross SE, Lowell BB, Wang Y, Goulding M, Ma Q.
Cell. 2014; 159(6):1417-32.
Understanding the switch from pain-to-itch in dermatitis.
Hachisuka J, Ross SE.
Neurosci Lett. 2014 Sep 5;579:188-9.
An SCN9A variant, known to cause pain, is now found to cause itch.
Snyder LM, Ross SE, Belfer I.
Pain. 2014; 155(9):1677-8.
Transplant restoration of spinal cord inhibitory controls ameliorates neuropathic itch.
Braz JM, Juarez-Salinas D, Ross SE, Basbaum AI.
J Clin Invest. 2014 Aug;124(8):3612-6.
Dynorphin acts as a neuromodulator to inhibit itch in the dorsal horn of the spinal cord.
Kardon AP, Polgár E, Hachisuka J, Snyder LM, Cameron D, Savage S, Cai X, Karnup S, Fan CR, Hemenway GM, Bernard CS, Schwartz ES, Nagase H, Schwarzer C, Watanabe M, Furuta T, Kaneko T, Koerber HR, Todd AJ, Ross SE.
Neuron. 2014 May 7;82(3):573-86.