The goal of our grant application is a functional and anatomic dissection of the neural pathways emanating from the mouse medial amygdala (MeA). This nucleus regulates many behaviors, including social memory, the response to predators and other stressors, and mating and aggression. The MeA is heterogeneous and contains many neuronal pools with distinct identities. One hypothesis to account for the functional diversity of the MeA is that different MeA neuronal pools serve distinct functions. Our previous work (funded by the prior grant period) and that of others has identified a small collection of aromatase-expressing neurons located in the posterodorsal component of the MeA. Both aromatase and the MeA are essential for the display of mating and aggression. Intriguingly, our work shows that there are more aromatase+ neurons in the MeA in males compared to females. We therefore hypothesize that aromatase+ MeA neurons influence the dimorphic displays of mating and aggression.
In Aim 1, we will use c-Fos expression to identify the behavioral and chemosensory stimuli that activate these neurons;our studies will be performed in an aromatase reporter mouse we have previously generated to allow sensitive co-labeling for c-Fos and aromatase.
In Aim 2, we will trace the connections of aromatase+ MeA neurons. We will use a Cre-dependent pseudorabies virus for trans-synaptic retrograde labeling, and a novel Cre-dependent neural tracer encoding virus we have developed for labeling the projections of aromatase+ neurons. These studies will be performed using a novel aromatase-Cre mouse strain we have engineered. We will also combine c-Fos labeling with cholera toxin B, a retrograde tracer, to determine if aromatase+ neurons activated by different stimuli project to distinct targets.
In Aim 3, we will use powerful optogenetic effectors to stimulate (channelrhodopsin2) and inhibit (halorhodopsin3) aromatase+ MeA neurons to determine the functional relevance of these cells to dimorphic displays of mating and aggression. Thus, our studies will provide insight into the neural pathways emanating from aromatase+ MeA neurons and their functional relevance in vivo. Health Relatedness: Neuro-psychiatric conditions often reflect dysfunction of neural circuitry at a gross or microscopic level, and these remain poorly understood and therapeutically intractable. The human amygdala is critical for recognition of social and emotional cues, and amygdalar dysfunction is thought to contribute to post-traumatic stress disorder and autism spectrum disorders. Our proposed work will shed light on the connectivity and functions of a subset of amygdalar neurons, thereby leading to an advance in basic scientific understanding of this region and the neural circuits within which it functions in health, and it may ultimately help guide future therapeutic or diagnostic applications for disorders of the amygdala.
Dysfunction of neuronal circuits is thought to underlie many devastating neuro-psychiatric conditions. Our basic research is focused on elucidating the connections and functions of the amygdala, a brain region that has been implicated in post-traumatic stress disorder and autism spectrum disorders. Our work will shed light on how the amygdala functions in health, and ultimately may help guide future therapeutic and diagnostic applications for amygdalar dysfunction.
|Yang, Taehong; Shah, Nirao M (2016) Molecular and neural control of sexually dimorphic social behaviors. Curr Opin Neurobiol 38:89-95|
|Delwig, Anton; Larsen, DeLaine D; Yasumura, Douglas et al. (2016) Retinofugal Projections from Melanopsin-Expressing Retinal Ganglion Cells Revealed by Intraocular Injections of Cre-Dependent Virus. PLoS One 11:e0149501|
|Bayless, Daniel W; Shah, Nirao M (2016) Genetic dissection of neural circuits underlying sexually dimorphic social behaviours. Philos Trans R Soc Lond B Biol Sci 371:20150109|
|Sokolowski, Katie; Esumi, Shigeyuki; Hirata, Tsutomu et al. (2015) Specification of select hypothalamic circuits and innate behaviors by the embryonic patterning gene dbx1. Neuron 86:403-16|
|Cheung, Clement C; Krause, William C; Edwards, Robert H et al. (2015) Sex-dependent changes in metabolism and behavior, as well as reduced anxiety after eliminating ventromedial hypothalamus excitatory output. Mol Metab 4:857-66|
|Unger, Elizabeth K; Burke Jr, Kenneth J; Yang, Cindy F et al. (2015) Medial amygdalar aromatase neurons regulate aggression in both sexes. Cell Rep 10:453-62|
|Nelson, Alexandra B; Hammack, Nora; Yang, Cindy F et al. (2014) Striatal cholinergic interneurons Drive GABA release from dopamine terminals. Neuron 82:63-70|
|Yang, Cindy F; Shah, Nirao M (2014) Representing sex in the brain, one module at a time. Neuron 82:261-78|
|Fraser, Eleanor J; Shah, Nirao M (2014) Complex chemosensory control of female reproductive behaviors. PLoS One 9:e90368|
|Morgan, Charles W; Julien, Olivier; Unger, Elizabeth K et al. (2014) Turning on caspases with genetics and small molecules. Methods Enzymol 544:179-213|
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