Funding provided by this grant has led to the establishment of a sophisticated infrastructure for evaluating the role of putative brain regions in nonhuman primate social behavior. Highly selective lesions of the amygdaloid complex and of the hippocampal formationhave been made in adult rhesus monkeys and in two week old infants.A unique aspect of this program is that all neonatal subjects are raised by their mothers following neurosurgery and experience daily periods of normal socialization. Both the social behavior and emotional responsiveness of adult and infant animal subjects have been extensively analyzed using quantitative behavioral analytic techniques. During the current funding period, we have also carried out two microPET studies of brain metabolism that opens the door to future noninvasive imaging studies of monkey brain function. We have also developed a new fear-potentiated startle apparatus for the rhesus monkey and have found, contrary to results in the rodent, that the amygdala is essential for learning a fear response but not for expressing a fear memory. The combined protocols for brain imaging, neurosurgery and behavioral analyses that have been developed are now being applied to other brain regions. Currently, a new group of animals with lesions of the orbitofrontal cortex are being studied. Finally, we have further developed the use of the allatostatin transient inactivation technique in rats and are now ready to begin studies with this technology in the rhesus monkey. For the proposed extension period, we have planned seven specific aims. These include: 1) To conclude longitudinal analyses of rhesus monkeys that received bilateral lesions of the amygdala or hippocampal formation at two weeks of age;2) To continue analyses of social and emotional behavior in a group of adult rhesus monkeys that were prepared with bilateral lesions of the orbitofrontal cortex;3) To prepare a new cohort of adult animals with lesions of the anterior cingulate cortex;4) To transfect the amygdala of a new cohort of adult rhesus monkeys with the receptor for allatostatin 5) To prepare a new cohort of infant animals either with permanent lesions of the orbitofrontal cortex and/or the anterior cingulate cortex;6) To carry out in vivo and postmortem morphological analyses of animals that received lesions of the amygdala and hippocampus as neonates;and 7) To carry out microPET studies with social stimuli to explore the organization of regions involved in the social brain.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37MH057502-15
Application #
8244507
Study Section
Special Emphasis Panel (NSS)
Program Officer
Simmons, Janine M
Project Start
1998-08-01
Project End
2014-03-31
Budget Start
2012-04-01
Budget End
2014-03-31
Support Year
15
Fiscal Year
2012
Total Cost
$699,566
Indirect Cost
$237,667
Name
University of California Davis
Department
Psychiatry
Type
Schools of Medicine
DUNS #
047120084
City
Davis
State
CA
Country
United States
Zip Code
95618
Hunsaker, Michael R; Amaral, David G (2014) A semi-automated pipeline for the segmentation of rhesus macaque hippocampus: validation across a wide age range. PLoS One 9:e89456
Hunsaker, Michael R; Scott, Julia A; Bauman, Melissa D et al. (2014) Postnatal development of the hippocampus in the Rhesus macaque (Macaca mulatta): a longitudinal magnetic resonance imaging study. Hippocampus 24:794-807
Bliss-Moreau, Eliza; Machado, Christopher J; Amaral, David G (2013) Macaque cardiac physiology is sensitive to the valence of passively viewed sensory stimuli. PLoS One 8:e71170
Bliss-Moreau, Eliza; Theil, Jacob H; Moadab, Gilda (2013) Efficient cooperative restraint training with rhesus macaques. J Appl Anim Welf Sci 16:98-117
Bliss-Moreau, Eliza; Moadab, Gilda; Bauman, Melissa D et al. (2013) The impact of early amygdala damage on juvenile rhesus macaque social behavior. J Cogn Neurosci 25:2124-40
Machado, Christopher J; Nelson, Eric E (2011) Eye-tracking with nonhuman primates is now more accessible than ever before. Am J Primatol 73:562-9
Bliss-Moreau, Eliza; Bauman, Melissa D; Amaral, David G (2011) Neonatal amygdala lesions result in globally blunted affect in adult rhesus macaques. Behav Neurosci 125:848-58
Amaral, David G (2011) The promise and the pitfalls of autism research: an introductory note for new autism researchers. Brain Res 1380:3-9
Machado, Christopher J; Bliss-Moreau, Eliza; Platt, Michael L et al. (2011) Social and nonsocial content differentially modulates visual attention and autonomic arousal in Rhesus macaques. PLoS One 6:e26598
Bliss-Moreau, E; Toscano, J E; Bauman, M D et al. (2011) Neonatal amygdala lesions alter responsiveness to objects in juvenile macaques. Neuroscience 178:123-32

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