Department of Neurobiology
Ross, Sarah E., Ph.D.
Associate Professor, Neurobiology
Address: W1456 BSTWR
   200 Lothrop Street
   Pittsburgh, PA 15213-2536
Telephone: 412-624-9178
Fax: 412-648-1441

Mission: The goal of our research is to functionally dissect the neural circuits that underlie pain and itch.

Approach: We use molecular genetic, electrophysiological and behavioral studies in mouse. This approach to gaining insight into the nervous system is compelling because pain and itch, which induce innate spinal reflexes, are likely to be mediated by genetically-encoded circuits that may be tractable for study. Furthermore, as we discover how activity drives adaptive changes in the excitability of circuits that mediate itch and pain, we may uncover principles of plasticity that have broad application through the nervous system.

Background: Itch and pain are sensory modalities that alert the organism to potential harm and trigger responses—scratching and withdrawal, respectively—that protect the body by separating it from harmful agents. These responses are initiated when noxious stimuli activate primary sensory neurons in the periphery, which convey this information to the spinal cord. Next, neural circuits within the dorsal horn of the spinal cord process and modulate this information prior to relaying it to the brain. Unfortunately, these circuits are almost completely uncharacterized, despite a pressing need to understand how their dysfunction can lead to chronic pathological conditions. Recent studies have supported the idea pain and itch are mediated by distinct neural circuits; however, the neurons involved are almost completely unknown. In addition, while it is clear that these aversive sensations inhibit one another, the neural basis for this phenomenon is unclear. Thus, there is a fundamental gap in our understanding of the basic wiring and logic of the spinal circuits that mediate pain and itch.

What we are doing: Our lab uses transcription factors, such as Bhlhb5, Bhlhb4 and Prdm8, as entry points to study the development and function of neural circuits underlying pain and itch. For instance, our work has identified a subset of inhibitory neurons (which we term B5-I neurons) that are required for normal itch sensation; mice lacking these neurons suffer from persistent pathological itch. This work provides the first evidence implicating a loss of inhibitory neurons within the dorsal horn in pathological itch (Fig. 1). Furthermore, B5-I neurons are the first component of an itch circuit to be labeled genetically, and so studying these neurons provides us with a unique opportunity to unravel itch circuits. We are now using this molecular handle to investigate the development of B5-I neurons and understand how they regulate itch.

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.

Sample Publications:

Kappa Opioid Receptor Distribution and Function in Primary Afferents.
Snyder LM, Chiang MC, Loeza-Alcocer E, Omori Y, Hachisuka J, Sheahan TD, Gale JR, Adelman PC, Sypek EI, Fulton SA, Friedman RL, Wright MC, Duque MG, Lee YS, Hu Z, Huang H, Cai X, Meerschaert KA, Nagarajan V, Hirai T, Scherrer G, Kaplan DH, Porreca F, Davis BM, Gold MS, Koerber HR, Ross SE.
Neuron. 2018 Sep 19;99(6):1274-1288.e6.

Wind-up in lamina I spinoparabrachial neurons: a role for reverberatory circuits.
Hachisuka J, Omori Y, Chiang MC, Gold MS, Koerber HR, Ross SE.
Pain. 2018 Aug;159(8):1484-1493.

Semi-intact ex vivo approach to investigate spinal somatosensory circuits.
Hachisuka J, Baumbauer KM, Omori Y, Snyder LM, Koerber HR, Ross SE.
Elife. 2016 Dec 19;5. pii: e22866.

Bhlhb5::flpo allele uncovers a requirement for Bhlhb5 for the development of the dorsal cochlear nucleus.
Cai X, Kardon AP, Snyder LM, Kuzirian MS, Minestro S, de Souza L, Rubio ME, Maricich SM, Ross SE.
Dev Biol. 2016 Jun 15;414(2):149-60.

Generation of a KOR-Cre knockin mouse strain to study cells involved in kappa opioid signaling.
Cai X, Huang H, Kuzirian MS, Snyder LM, Matsushita M, Lee MC, Ferguson C, Homanics GE, Barth AL, Ross SE.
Genesis. 2016 Jan;54(1):29-37.

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.

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