Dissertation/Thesis Abstract

Embryonic Transcription Factor Expression Predicts Neuronal Identity and Innate Behavioral Activation Patterns in the Limbic System
by Lischinsky, Julieta E., Ph.D., The George Washington University, 2017, 128; 10263849
Abstract (Summary)

Instinctive behaviors such as mating and aggression are key for the survival and propagation of species. As innate behaviors manifest without prior training, there must be embryonic genetic mechanisms that specify these innate behavioral circuits. Focusing on the MeA and hypothalamus, both major integration centers of olfactory inputs, first, we sought to elucidate the link between embryonic transcription factor expression, neuronal identity and innate behavioral activation patterns in the MeA, and second, the link between embryonic transcription factor expression and instinctive behavioral activation patterns in hypothalamic subnuclei. Using mice as a model organism, we observed that the MeA progenitor niche in the preoptic area (POA) is comprised of distinct progenitor populations differentially marked by the transcription factors Dbx1 and Foxp2. Both embryonically and postnatally, Dbx1-derived and Foxp2+ subpopulations remain spatially segregated. We also observed that Dbx1-derived and Foxp2+ neurons differentially express sets of sex-steroid pathway proteins. Furthermore, both subpopulations differed in their intrinsic and extrinsic electrophysiological properties. Additionally, behavioral activation patterns were investigated in both subpopulations by determining the co-expression of the immediate early gene c-fos, an indirect marker of neuronal activity. During aggressive encounters, both Dbx1-derived and Foxp2+ neurons were activated in male and female mice; however, during mating cues, Dbx1-derived neurons in male and female mice were activated while only Foxp2+ neurons in male mice were activated and not in female mice. This denotes sex-specific differences in behavioral activation patterns in the MeA. Thus, parcellation of MeA neuronal subpopulations based on developmental genetics predicts molecular, electrophysiological, and behavioral specificity. Secondly, we were interested in determining whether embryonic transcription factor expression would be predictive of innate behavioral activation patterns in other limbic system structures implicated in the generation of innate behaviors such as the hypothalamus. Interestingly, we observed the presence of Dbx1-derived neurons in the lateral (LH), arcuate (Arc) and ventromedial (VMH) hypothalamic subnuclei. As Foxp2+ neurons are not present in the hypothalamus, we only analyzed Dbx1-derived neurons in these three hypothalamic regions. We show that Dbx1-derived neurons are activated in these structures during mating and aggression in both male and female mice. Thus, embryonic transcription factor expression in the hypothalamus is also linked to postnatal behavioral activation patterns. Taken together our findings indicate that embryonic transcription factor expression is predictive of behavioral activation patterns in the limbic system. We found that progenitor populations present in the same region but expressing distinct transcription factors, can generate MeA postnatal diversity based on molecular, electrophysiological and behavioral activation patterns. Furthermore, this can be generalized to other limbic system structures such as the hypothalamus, in which embryonic transcription factor expression of Dbx1 is also predictive of activation patterns during instinctive behavioral cues.

Indexing (document details)
Advisor: Corbin, Joshua G., Gallo, Vittorio
Commitee: LaMantia, Anthony S., Liu, Judy, Manzini, Chiara, Wu, Guangying
School: The George Washington University
Department: Molecular Medicine
School Location: United States -- District of Columbia
Source: DAI-B 78/08(E), Dissertation Abstracts International
Subjects: Neurosciences
Keywords: Amygdala, Development, Hypothalamus, Innate behaviors
Publication Number: 10263849
ISBN: 9781369685725
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