This renewal application is focused on the study of the development of the basolateral complex and medial nucleus of the amygdala. Collectively these nuclei regulate major aspects of limbic system function. Our previous studies have identified distinct progenitor pools in the developing telencephalon that contribute to postnatal neuronal cell diversity in these amygdala subdivisions. Based on this work, in this project we will test two hypotheses. First, we will test the hypothesis that embryonic transcriptional factor expression diversity within amygdala progenitor pools underlies differential postnatal amygdala neuronal subtype fate and patterns of axonal connectivity. Second, we will test the hypothesis that key transcription factors that are expressed in these progenitor domains are required for the development and/or connectivity of postnatal amygdala neurons that are derived from these populations. Testing of these hypotheses will be accomplished using a combination cutting edge approaches including genetic fate mapping, electrophysiology, axonal tracing and conditional loss of function.

Public Health Relevance

The mammalian amygdala is a central structure of the brain's limbic system, a brain circuit that coordinates appropriate behavioral responses to stimuli with emotional and motivational salience. Amygdala dysfunction is associated with numerous brain disorders including addictive behavior and developmental disorders such as autism spectrum disorders. This proposal is directed toward understanding the genetic and cellular basis of amygdala development, and thus will provide valuable insight into human disorders in which amygdala function is altered.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
3R01DA020140-09S1
Application #
8661453
Study Section
Neurogenesis and Cell Fate Study Section (NCF)
Program Officer
Wu, Da-Yu
Project Start
2005-07-01
Project End
2016-01-31
Budget Start
2013-02-01
Budget End
2014-01-31
Support Year
9
Fiscal Year
2013
Total Cost
$11,016
Indirect Cost
$816
Name
Children's Research Institute
Department
Type
DUNS #
143983562
City
Washington
State
DC
Country
United States
Zip Code
20010
Sokolowski, Katie; Tran, Tuyen; Esumi, Shigeyuki et al. (2016) Molecular and behavioral profiling of Dbx1-derived neurons in the arcuate, lateral and ventromedial hypothalamic nuclei. Neural Dev 11:12
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
Jones, Kevin S; Corbin, Joshua G; Huntsman, Molly M (2014) Neonatal NMDA receptor blockade disrupts spike timing and glutamatergic synapses in fast spiking interneurons in a NMDA receptor hypofunction model of schizophrenia. PLoS One 9:e109303
Vislay, Rebecca L; Martin, Brandon S; Olmos-Serrano, Jose Luis et al. (2013) Homeostatic responses fail to correct defective amygdala inhibitory circuit maturation in fragile X syndrome. J Neurosci 33:7548-58
Sokolowski, Katie; Corbin, Joshua G (2012) Wired for behaviors: from development to function of innate limbic system circuitry. Front Mol Neurosci 5:55
Corbin, Joshua G; Butt, Simon J B (2011) Developmental mechanisms for the generation of telencephalic interneurons. Dev Neurobiol 71:710-32
Cocas, Laura A; Georgala, Petrina A; Mangin, Jean-Marie et al. (2011) Pax6 is required at the telencephalic pallial-subpallial boundary for the generation of neuronal diversity in the postnatal limbic system. J Neurosci 31:5313-24
Gray, Paul A; Hayes, John A; Ling, Guang Y et al. (2010) Developmental origin of preBotzinger complex respiratory neurons. J Neurosci 30:14883-95
Olmos-Serrano, Jose Luis; Paluszkiewicz, Scott M; Martin, Brandon S et al. (2010) Defective GABAergic neurotransmission and pharmacological rescue of neuronal hyperexcitability in the amygdala in a mouse model of fragile X syndrome. J Neurosci 30:9929-38
Carney, Rosalind S E; Cocas, Laura A; Hirata, Tsutomu et al. (2009) Differential regulation of telencephalic pallial-subpallial boundary patterning by Pax6 and Gsh2. Cereb Cortex 19:745-59

Showing the most recent 10 out of 15 publications