Accurate perception and appropriate responses to sensory stimuli are critical brain functions for maintaining homeostasis and for survival. In addition, abnormal responses to sensory stimuli cause sensory hypersensitivity in neuropsychiatric conditions such as posttraumatic stress disorder, autism, migraine and panic disorder. In my research program, I aim to dissect sensory processing neural circuits that relay multi-modal sensory stimuli to the amygdala during threat perception. One candidate brain structure that relay aversive sensory input to the amygdala is the pontine parabrachial nucleus (PBN), because the neurons in the PBN directly transmit aversive sensory information from sensory modalities to the central nucleus of the amygdala (CeA) and to the bed nucleus of the stria terminalis (BNST). I will combine state-of-the-art molecular, physiological, behavioral, and imaging techniques to advance our understanding of the neural bases for the sensory processing of threat.
Identify specific markers in the PBN neurons that are functionally relevant to the transmission of aversive sensory information to the amygdala: First, we will identify the specific markers in the PBN from Allan Brain Atlas, then we will generate cre-driver mouse lines, or obtain cre-driver lines from available sources. Second, we will further define the projections of PBN-specific neurons using virus-mediated anterograde/retrograde tracing tools.
Dissect neural circuits for sensory perception of threat using PBN-specific cre-driver lines: We will functionally dissect neural circuits involved in relaying threat signal by manipulating and monitoring specific population of neurons in the PBN using viral delivery of cell type-specific circuit dissection tools, such as optogenetics, chemogenetics, and in vivo calcium imaging.
Define the cell types of the direct downstream neurons from the PBN neurons, and characterize their target-specific roles in sensory perception of threat: We will identify molecular identities of direct-recipient neurons from the PBN neurons using cell-type specific transcriptome profiling method (Ribotag). This will not only enable us to further dissect downstream neural circuits as described in 1) and 2), but also make us to identify novel markers for modulating the specific neural circuits that relay aversive sensory signals, which may serve as novel therapeutic candidates for treating sensory hypersensitivity traits found in psychiatric disorders.
Han S, Yu FH, Schwartz MD, Linton JD, Bosma MM, Hurley JB, Catterall WA, de la Iglesia HO. (2012) NaV1.1 channels are critical for intercellular communication in the suprachiasmatic nucleus and normal circadian rhythms. Proceedings of the National Academy of Sciences (USA) 109(6):E368-77.
Han S, Tai C, Westenbroek RE, Cheah C, Yu FH, Rubenstein JL, Scheuer T, de la Iglesia HO, Catterall WA. (2012) Autistic-like behaviors in Scn1a+/- mice and rescue by enhanced GABA-mediated neurotransmission. Nature 489(7416):385-90.
Han S, Tai C, Jones CJ, Scheuer T, Catterall WA. (2014) Enhancement of Signaling by GABAA Receptors Having α2,3-Subunits Ameliorates Behavioral Deficits in a Mouse Model of Autism. Neuron 81(6):1282-9.
Cater ME, Han S, Palmiter RD. (2015) Parabrachial CGRP-expressing neurons mediate conditioned taste aversion. Journal of Neuroscience 35(11):4582-6.
Rubinstein M*, Han S*, Tai C*, Westenbroek RE, Scheuer T, Catterall WA. (2015) Dissecting the Phenotypes of Dravet Syndrome by Gene Deletion. Brain 138(8):2219-33. *co-first authors
Han S, Soleiman MT, Soden ME, Zweifel LS, Palmiter RD. (2015) Elucidating an Affective Pain Circuit that Creates a Threat Memory. Cell 162(2):363-374.
Campos CA, Bowen AJ, Han S, Wisse BE, Palmiter RD, Schwartz MW. (2017) Cancer-induced anorexia and malaise are mediated by CGRP neurons in the parabrachial nucleus. Nat Neurosci 20(7):934-942.