Characterization of the Circuits Mediating Innate Reproductive and Defensive Behaviors from the Amygdala to the Hypothalamus

All metazoan organisms must reproduce and defend themselves in order to survive as individuals and as a species. These innate behaviors are so crucial that they are "hard-wired" into the brain during the animal’s development. They are also released primarily by the olfactory stimuli detected by the AOB, which synapses into the MEA. The MEA in turn projects to the medial hypothalamic behavior control column, which contains a series of nuclei orchestrating either reproductive or defensive behaviors. These amygdalar-hypothalamic projections are topographically organized, and the sub-circuitries controlling reproduction and defense are segregated both functionally and anatomically. The topographically organized projections suggest that these neural pathways for reproduction and defense are likely genetically determined, but genes that might control their wiring have not yet been identified. Such a parallel circuit organization with very few cross-talks between the two sub-circuits also poses the problem of how rapid decisions between competing reproductive and defensive behaviors are made by organisms faced with conflicting cues. Using oligonucleotide microarrays and laser-capture microdissection, I identified that several LIM homeodomain transcription factors mark different regions of the MEA involved in either reproductive or defensive behaviors. I have characterized the projections of these neurons to the hypothalamus, using both genetically encoded anterograde and traditional retrograde tracers. I have also carried out behavioral experiments to assess their differential activations by reproductive and defensive stimuli. My results indicate that Lhx6 delineates a reproductive pathway, which involves neurons in both MEApd and BSTpr, and their projections to the three reproductive nuclei in the hypothalamic medial behavioral control column (MPN, VMHvl and PMv). Further analysis reveals, counter-intuitively, that VMHvl receives inhibitory projections from this reproductive pathway, and a convergent excitatory projection from neurons in MEApv that are activated by a predator odor. The results suggest that this point-of-convergence may serve to "gate" the expression of reproductive behavior, under conditions where animals are exposed to threatening stimuli. Thus, my data identifies a potential neural substrate within the hypothalamus for controlling behavioral decisions in the face of conflicting cues and a transcription factor family that may contribute to the development of this substrate.</p

Oxytocin Mediates Entrainment of Sensory Stimuli to Social Cues of Opposing Valence

Meaningful social interactions modify behavioral responses to sensory stimuli. The neural mechanisms underlying the entrainment of neutral sensory stimuli to salient social cues to produce social learning remain unknown. We used odor-driven behavioral paradigms to ask if oxytocin, a neuropeptide implicated in various social behaviors, plays a crucial role in the formation of learned associations between odor and socially significant cues. Through genetic, optogenetic, and pharmacological manipulations, we show that oxytocin receptor signaling is crucial for entrainment of odor to social cues but is dispensable for entrainment to nonsocial cues. Furthermore, we demonstrate that oxytocin directly impacts the piriform, the olfactory sensory cortex, to mediate social learning. Lastly, we provide evidence that oxytocin plays a role in both appetitive and aversive social learning. These results suggest that oxytocin conveys saliency of social stimuli to sensory representations in the piriform cortex during odor-driven social learning.National Science Foundation (U.S.) (Graduate Research Fellowship, grant 1122374)National Research Foundation of Korea (Basic Science Research Program)Human Frontier Science Program (Strasbourg, France) (Postdoctoral fellowships, LT000692/2014-L)National Institute of Mental Health (U.S.) (award number R01MH106497)Massachusetts Institute of Technology. Simons Center for the Social Brain (seed grant (020362-056)

Molecular signatures of neural connectivity in the olfactory cortex

The ability to target subclasses of neurons with defined connectivity is crucial for uncovering neural circuit functions. The olfactory (piriform) cortex is thought to generate odour percepts and memories, and odour information encoded in piriform is routed to target brain areas involved in multimodal sensory integration, cognition and motor control. However, it remains unknown if piriform outputs are spatially organized, and if distinct output channels are delineated by different gene expression patterns. Here we identify genes selectively expressed in different layers of the piriform cortex. Neural tracing experiments reveal that these layer-specific piriform genes mark different subclasses of neurons, which project to distinct target areas. Interestingly, these molecular signatures of connectivity are maintained in reeler mutant mice, in which neural positioning is scrambled. These results reveal that a predictive link between a neuron’s molecular identity and connectivity in this cortical circuit is determined independent of its spatial position