The research and career development plans proposed in this application will expand the candidate's expertise in neuropharmacology, normal and abnormal socioemotional development, epileptology, and magnetic resonance imaging (MRI) as applied to neurodevelopmental disorders such as autism, mental retardation, and cerebral palsy. The Research Plan proposed will take advantage of the recent evidence that dysfunction in medial temporal lobes, and the amygdala in particular, may be an etiological factor in autism. The goal of the application is to investigate the role of amygdala and its specific subdivisions for socioemotional behavior, and to identify the critical periods and neural triggers for developmental abnormalities in an animal model of autism.
Specific Aim 1 concentrates on the effects of pharmacologically induced imbalances in neurotransmission in amygdala on social interactions in infant animals.
Specific Aim 2 will compare the effects of drugs (as obtained in Aim 1) with the effects of discrete lesions of subregions of amygdala, damaged by axon-sparing lesions.
Specific Aim 3 will evaluate the effects of early prolonged seizures, known to disrupt the function of amygdala and its projection network, on the neurodevelopmental behavioral outcomes. The experiments designed to pursue these aims will provide an opportunity for the candidate to gain both theoretical and practical expertise in the combined use of pharmacological, physiological, and MRI approaches to the study of the animal models. The candidate's background in behavioral research will be applied to the analyses of various components of socioemotional interactions of infant and juvenile animals in dyads and the assessment of their cognitive functions. The career development plan will facilitate a substantial shift in the candidate's research capabilities and scope, so that it will become possible for her to build an independent research program devoted to the identification of neural mechanisms underlying autism and other developmental disorders. The ability to evaluate the multifactorial impact of pharmacological interventions in animal models will prepare the candidate to pursue research on animal models of neurodevelopmental disorders and place her research skills in the context of pharmacology, epileptology, and physiology. Structured activities and short courses will guide the development of expertise in these areas necessary for the proposed studies as well as for the long-term career advancement of the candidate as a versatile neuroscientist. ? ?

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Scientist Development Award - Research (K02)
Project #
5K02HD042269-02
Application #
6751700
Study Section
Pediatrics Subcommittee (CHHD)
Program Officer
Kau, Alice S
Project Start
2003-06-01
Project End
2008-05-31
Budget Start
2004-06-01
Budget End
2005-05-31
Support Year
2
Fiscal Year
2004
Total Cost
$100,440
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
Malkova, Ludise; Alvarado, Maria C; Bachevalier, Jocelyne (2016) Effects of Separate or Combined Neonatal Damage to the Orbital Frontal Cortex and the Inferior Convexity on Object Recognition in Monkeys. Cereb Cortex 26:618-27
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
Malkova, Ludise; Forcelli, Patrick A; Wellman, Laurie L et al. (2015) Blockade of glutamatergic transmission in perirhinal cortex impairs object recognition memory in macaques. J Neurosci 35:5043-50
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
Bachevalier, Jocelyne; Malkova, Ludise (2006) The amygdala and development of social cognition: theoretical comment on Bauman, Toscano, Mason, Lavenex, and Amaral (2006). Behav Neurosci 120:989-91
Belcher, Annabelle M; Harrington, Rebecca A; Malkova, Ludise et al. (2006) Effects of hippocampal lesions on the monkey's ability to learn large sets of object-place associations. Hippocampus 16:361-7
Malkova, L; Heuer, E; Saunders, R C (2006) Longitudinal magnetic resonance imaging study of rhesus monkey brain development. Eur J Neurosci 24:3204-12
Wellman, Laurie L; Gale, Karen; Malkova, Ludise (2005) GABAA-mediated inhibition of basolateral amygdala blocks reward devaluation in macaques. J Neurosci 25:4577-86