Pain and Plasticity: spike sorting of peripheral neural activity underlying nociceptive sensitization in Manduca sexta
By: Christian Valtierra
Department: Physiology & Behavioral Biology
Faculty Advisor: Dr. Megumi Fuse
Nociceptive sensitization is an evolutionarily ancient form of non-associative learning and memory. It is characterized by a heightened state of arousal and decrease in the sensory threshold required to engage in defensive (nocifensive) behaviors following exposure to an intensely noxious or harmful stimulus. Injury-induced maladaptive plasticity in humans is hypothesized to be the basis for neuropathic pain conditions such as allodynia and hyperalgesia. Because key aspects of the neural and molecular mechanisms of underlying injury-induced sensory processing and neural plasticity are conserved, the relatively simple nervous systems of invertebrates make them attractive models for biomedical research and development. The hornworm, Manduca sexta, displays rapid nocifensive “striking” behavior that accurately targets the cite of noxious stimulation of the abdominal body wall. Nociceptive sensitization of the defensive strike response has been induced in vivo in our lab, by using a behavioral assay that detects the long-lasting decrease in sensory threshold following a noxious stimulus relative to stimulus naïve control group. These results have been successfully recapitulated in lab with an in vitro extracellular electrophysiological assay, showing that the state of sensitization is encoded by an increase in the firing frequency of interneurons within the central nervous system, rather than changes in peripheral nociceptor signaling. In this work, we perform source separation techniques on pre-existing extracellular electrophysiological data from the peripheral nerve to (a) extract the number of sensory neurons activated during mechanical stimulation, and (b) to verify that sensitization has not occurred in these peripheral neurons. Because it has previously been shown that gross electrical activity recorded peripherally does not appear to change in response to behavioral sensitization, we hypothesize that no individual peripheral sensory neurons are sensitized. This data provides the beginning characterization of the neural circuitry as well as the plasticity involved in coordinating this defensive behavior.