The proposal aims to identify the neural substrates in the brain that are responsible for abnormal socio-emotional behavior. This understanding is vital for developing both diagnostic and therapeutic approaches to identify and treat the abnormal brain circuitry in neuropsychiatric conditions such as affective and anxiety disorders. The field of social behavior research still lacks appropriate animal models for social pathology that leads to inappropriate aggression, social anxiety/phobias, social withdrawal/detachment, impulsivity, or defensiveness. The study of the neurobiology of social behavior in non-rodent models is especially promising since the impairment in social interactions and emotional processing generates symptomatology that resembles psychopathology observed in human patients. Moreover these studies will permit an analysis of social interactions at a level not feasible in rodents. Therefore, this work promises to substantially advance our understanding of the neural substrates of human social interactions in the norm and pathology with a special relevance to anxiety and depression. The proposed research seeks to investigate the novel components of the amygdala-based network that regulates socioemotional responses in order to account for imbalances that can give rise to psychopathology in the absence of structural lesions. The effects of the DLSC manipulations on the vulnerability to behavioral abnormalities evoked by disinhibition within nuclei of the amygdala will be analyzed to determine the role of DLSC in mediating and/or modulating the influence of the amygdala circuitry. An understanding of the functional relationship between the amygdala-derived and colliculus- derived regulation of defensive and aggressive emotional tone is expected to reveal novel targets for both etiology and therapeutic intervention for affective and anxiety disorders.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH084069-02
Application #
7676883
Study Section
Special Emphasis Panel (ZMH1-ERB-Z (03))
Program Officer
Quinn, Kevin J
Project Start
2008-08-19
Project End
2013-04-30
Budget Start
2009-05-01
Budget End
2010-04-30
Support Year
2
Fiscal Year
2009
Total Cost
$383,750
Indirect Cost
Name
Georgetown University
Department
Pharmacology
Type
Schools of Medicine
DUNS #
049515844
City
Washington
State
DC
Country
United States
Zip Code
20057
Forcelli, Patrick A; Wellman, Laurie L; Malkova, Ludise (2017) Blockade of glutamatergic transmission in the primate basolateral amygdala suppresses active behavior without altering social interaction. Behav Neurosci 131:192-200
Forcelli, Patrick A; DesJardin, Jacqueline T; West, Elizabeth A et al. (2016) Amygdala selectively modulates defensive responses evoked from the superior colliculus in non-human primates. Soc Cogn Affect Neurosci 11:2009-2019
Wellman, Laurie L; Forcelli, Patrick A; Aguilar, Brittany L et al. (2016) Bidirectional Control of Social Behavior by Activity within Basolateral and Central Amygdala of Primates. J Neurosci 36:8746-56
DesJardin, Jacqueline T; Holmes, Angela L; Forcelli, Patrick A et al. (2013) Defense-like behaviors evoked by pharmacological disinhibition of the superior colliculus in the primate. J Neurosci 33:150-5
Holmes, Angela L; Forcelli, Patrick A; DesJardin, Jacqueline T et al. (2012) Superior colliculus mediates cervical dystonia evoked by inhibition of the substantia nigra pars reticulata. J Neurosci 32:13326-32
Malkova, Ludise; Mishkin, Mortimer; Suomi, Stephen J et al. (2010) Long-term effects of neonatal medial temporal ablations on socioemotional behavior in monkeys (Macaca mulatta). Behav Neurosci 124:742-60