Pisansky, Marc2016-10-252016-10-252016-08https://hdl.handle.net/11299/182773University of Minnesota Ph.D. dissertation. August 2016. Major: Neuroscience. Advisor: Jonathan Gewirtz. 1 computer file (PDF); vi, 116 pages.Empathy, the capacity to infer the emotional state of another, represents a normal process of social cognition that is impaired in several psychiatric diseases. This dissertation research investigates (1) behavioral indices and features of empathy in mice, (2) the role of the neuropeptide oxytocin in mouse empathy, and (3) empathic and other endophenotypes in an epigenetic mouse model of autism spectrum disorders (ASDs). Empathy was modeled using a novel set of behavioral paradigms that measure fear transmitted from a distressed “demonstrator” mouse to an “observer” conspecific. Socially transmitted fear was influenced by the sex of the observer, familiarity to the demonstrator, and distress vocalizations emitted from the demonstrator. Repeated observation of a distressed conspecific elicited a switch from freezing to escape fear behaviors that was specific to familiar conspecifics. Oxytocin – whether exogenously applied or released via chemogenetic stimulation – enhanced socially transmitted fear in unfamiliar mice, whereas oxytocin receptor antagonism reduced this empathic behavior in familiar mice. Genetically-modified mice lacking chromodomain helicase DNA-binding 5 (Chd5), a chromatin remodeler that regulates neurodevelopmental processes, exhibited specific impairments in these empathic behaviors. Chd5-/- mice further displayed characteristic socio-communicative and neophobic behaviors reminiscent of ASD symptomology. Cortical tissue from Chd5-/- mice revealed altered transcriptional expression and neuron-level morphological variations characteristic of ASD etiology and pathophysiology. Thus, this research furthers our understanding of neural and epigenetic contributions to neurodevelopment and social cognition, and provides clues to understanding empathy and treating psychiatric disease.enAutismEmpathyEpigeneticsMouseOxytocinThesis or Dissertation