The hippocampal formation is a multicomponent region of the medial temporal lobe that has been implicated in declarative and relational memory processing. Our research program has investigated the connectivity and chemical neuroanatomy of the adult nonhuman primate hippocampal formation. Completion of our current studies, together with the work of other laboratories, has largely accomplished the goal of clarifying the basic functional organization of the adult primate hippocampal formation. With this application, we enter a new phase of research to investigate the postnatal structural development and functional maturation of the primate hippocampal formation. We begin this program of studies by addressing four specific aims. First, we will characterize the organization and maturity of the major input and output circuitry of the hippocampus at birth. We will do this by placing anterograde and retrograde neuroanatomical tracer injections in the entorhinai cortex of neonatal monkeys. Second, we will conduct stereological studies, measuring the volume of hippocampal regions, counting neuron numbers, measuring neuron sizes, and quantifying cell proliferation and neurogenesis, at different ages throughout postnatal development. This work will define the temporal pattern of postnatal development, and specify the age at which several morphological characteristics of the monkey hippocampal formation become adult-like. Third, we will use histochemical and immunohistochemical techniques to characterize the neurochemical development of the monkey hippocampal formation over the first year of life and compare this with the adult pattern. Finally, we will study the potential neuroanatomical reorganization that may subserve the partial recovery of declarative memory function observed in humans with early hippocampal damage. We will investigate this by placing neuroanatomical tracer injections in the entorhinai cortex and the CA3 hippocampal field of normal one-year old monkeys and one-year-old monkeys that received neonatal lesions of the CA1 field of the hippocampus. Taken together, these experiments will provide essential information on the postnatal maturation of the functional organization of the primate hippocampal formation. Our findings will have broad implications for the study of normal memory processes, including infantile amnesia, as well as human neurodevelopmental and genetic disorders, such as autism, schizophrenia and epilepsy.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS016980-26
Application #
7215623
Study Section
Neurobiology of Learning and Memory Study Section (LAM)
Program Officer
Babcock, Debra J
Project Start
1994-02-01
Project End
2010-01-31
Budget Start
2007-02-01
Budget End
2008-01-31
Support Year
26
Fiscal Year
2007
Total Cost
$511,055
Indirect Cost
Name
University of California Davis
Department
Psychiatry
Type
Schools of Medicine
DUNS #
047120084
City
Davis
State
CA
Country
United States
Zip Code
95618
Chareyron, Loïc J; Banta Lavenex, Pamela; Amaral, David G et al. (2017) Functional organization of the medial temporal lobe memory system following neonatal hippocampal lesion in rhesus monkeys. Brain Struct Funct 222:3899-3914
Chareyron, Loïc J; Amaral, David G; Lavenex, Pierre (2016) Selective lesion of the hippocampus increases the differentiation of immature neurons in the monkey amygdala. Proc Natl Acad Sci U S A 113:14420-14425
Scott, Julia A; Grayson, David; Fletcher, Evan et al. (2016) Longitudinal analysis of the developing rhesus monkey brain using magnetic resonance imaging: birth to adulthood. Brain Struct Funct 221:2847-71
Coveñas, R; González-Fuentes, J; Rivas-Infante, E et al. (2015) Developmental study of vitamin C distribution in children's brainstems by immunohistochemistry. Ann Anat 201:65-78
Lee, Joshua K; Nordahl, Christine W; Amaral, David G et al. (2015) Assessing hippocampal development and language in early childhood: Evidence from a new application of the Automatic Segmentation Adapter Tool. Hum Brain Mapp 36:4483-96
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
Cebada-Sánchez, S; Insausti, R; González-Fuentes, J et al. (2014) Distribution of peptidergic populations in the human dentate gyrus (somatostatin [SOM-28, SOM-12] and neuropeptide Y [NPY]) during postnatal development. Cell Tissue Res 358:25-41
Amaral, David G; Kondo, Hideki; Lavenex, Pierre (2014) An analysis of entorhinal cortex projections to the dentate gyrus, hippocampus, and subiculum of the neonatal macaque monkey. J Comp Neurol 522:1485-505
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
Schumann, Cynthia Mills; Nordahl, Christine Wu (2011) Bridging the gap between MRI and postmortem research in autism. Brain Res 1380:175-86

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