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Principal Investigator: Allan I. Basbaum
Organization: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
Fiscal Year: 2024
Award: $922,471
Funding agency: National Institute of Neurological Disorders and Stroke
Despite tremendous progress in our understanding of the primary sensory neurons and spinal cord
interneuronal circuits that respond to and transmit pain and itch-provoking stimuli, how these stimuli are
interpreted by the brain to produce the perceptions of pain and itch are still unclear. To a great extent, this gap
in our knowledge reflects the much more limited information that we have about the projection neurons that
carry the information from the spinal cord to the brain. That gap is critical as it is the signals carried by the
projection neurons that are “read” by the brain and that ultimately lead to a perception of pain or itch, and to
their various submodalities (heat, cold, mechanical, etc.). Our research program is multidisciplinary, using
novel viral, genetic and functional (electrophysiological, behavioral and imaging) approaches to characterize
the properties of the projection neurons, the circuits that engage them, their supraspinal targets and the
functional consequence of their activity. An important focus of the research program is on the question of
convergence or segregation of the circuits that respond to painful or itch-provoking stimuli and the extent to
which these circuits are altered in the setting of injury. Our program includes several highly innovative
experiments that for the first time will not only determine the molecular heterogeneity of the projection neurons,
but will also examine the responses of populations of neurons in the brain to activity in the projection neurons.
Defining molecular subtypes of projection neurons and the development of Cre-expressing mice based on
these molecular features will permit a host of experiments, including viral-based retrograde (rabies) and
anterograde (HSV) tracing of circuits that influence subsets of projection neurons, as well as the behavioral
consequence of selective ablation, or DREADD-mediated activation/inhibition of these neurons. Finally, using
incredibly powerful Ca2+ imaging techniques that signal the activity of populations of neurons in awake, freely
moving mice, we will obtain new information on the behavioral correlates of algogen and pruritogen-evoked
supraspinal activity. Using novel behavioral paradigms our program will also provide important insights into the
processes through which noxious, and even innocuous stimuli (in the setting of injury), are interpreted as
painful. These new approaches will provide information about the quality of the pain that the animal
experiences and also offer a powerful validation of the mouse models of chronic pain and itch and their
translatability to the human condition.
Terms: <Ablation><Afferent Neurons><Behavioral><Behavioral Paradigm><Brain><Brain Nervous System><Cell Communication and Signaling><Cell Signaling><Cell Transplantation><Connector Neuron><DREADDs><Development><Electrophysiology><Electrophysiology (science)><Encephalon><Genetic><HSV><Herpes Simplex Virus><Herpes labialis Virus><Heterogeneity><Human><Image><Imaging Procedures><Imaging Technics><Imaging Techniques><Injury><Intercalary Neuron><Intercalated Neurons><Interneurons><Internuncial Cell><Internuncial Neuron><Intracellular Communication and Signaling><Itching><Knowledge><Mechanics><Mediating><Medulla Spinalis><Mice><Mice Mammals><Modern Man><Molecular><Murine><Mus><Nerve Cells><Nerve Unit><Neural Cell><Neuranatomies><Neuranatomy><Neuroanatomies><Neuroanatomy><Neurocyte><Neurology><Neurons><Neurophysiology / Electrophysiology><Pain><Pain quality><Painful><Population><Process><Property><Pruritic Disorder><Pruritis><Pruritus><Rabies><Research><Sensory Neurons><Signal Transduction><Signal Transduction Systems><Signaling><Simplexvirus><Spinal Cord><Stimulus><Time><Transmission><Validation><Viral><animal pain><awake><biological signal transduction><cell imaging><cellular imaging><cellular transplant><chronic itch><chronic pain><chronic pain control><chronic pain intervention><chronic pain management><chronic pain therapy><chronic pain treatment><chronic pruritus><designer receptors exclusively activated by designer drugs><developmental><electrophysiological><experience><experiment><experimental research><experimental study><experiments><expression subtypes><imaging><injuries><innovate><innovation><innovative><insight><itch sensation><lyssa><mechanic><mechanical><molecular sub-types><molecular subsets><molecular subtypes><mouse model><multidisciplinary><murine model><neuronal><new approaches><novel><novel approaches><novel strategies><novel strategy><pain perception><programs><response><segregation><transmission process><treat chronic pain><validations>