The primate amygdala is a complex brain region comprised of 13 nuclei and cortical regions in the rostral portion of the medial temporal lobe. This grant has funded studies with the overarching goal of defining the cytoarchitectonic organization and intrinsic and extrinsic connections of the macaque monkey amygdaloid complex. We have also been investigating neuropathology in the autistic amygdala. We reported that the amygdala in typically developing boys undergoes a 40% increase in volume between 7 and 18 years of age. This expansion occurs at a time when the cerebral volume decreases by about 10%. In boys with autism, the amygdala reaches its adult size by 7 years and does not increase thereafter. Given the association of the amygdala with a variety of psychiatric disorders including anxiety, depression, autism and schizophrenia, many of which are first manifest during the peripubertal period, it would be valuable to determine the morphological features of the amygdala's postnatal development. It is not feasible, however, to carry out this type of analysis in postmortem human brains. Thus, with this renewal we will begin studies to investigate the postnatal development of the macaque amygdala. First, we will carry out a longitudinal magnetic resonance imaging study of the brains of developing male and female rhesus monkeys to determine whether the dramatic and disproportionate growth of the amygdala in boys is also a feature of macaque development. Second, we will quantitatively analyze the emergence of species typical behaviors in the imaged animals.Third, we will implement modern design-based stereological techniques to measure the volume, count neuron number, and characterize neuron morphology in the amygdala throughout postnatal development. Fourth, we will use histochemical and immunohistochemical techniques to characterize the postnatal development of four major neurotransmitter systems (i.e., glutamatergic, GABAergic, cholinergic and serotonergic) in the amygdala. In addition, we will investigate the development of myelination and the expression of non-phosphorylated neurofilaments and synaptic markers (synaptophysin). Finally, we will use the Golgi technique and intracellular labeling of neurons in the in vitro slice preparation to quantify the maturation of dendrites in the major nuclei of the amygdaloid complex. This work provides essential normative data to study influences like circulating hormones or social experience on amygdala maturation.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
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Neurobiology of Motivated Behavior Study Section (NMB)
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Vicentic, Aleksandra
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University of California Davis
Schools of Medicine
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Avino, Thomas A; Barger, Nicole; Vargas, Martha V et al. (2018) Neuron numbers increase in the human amygdala from birth to adulthood, but not in autism. Proc Natl Acad Sci U S A 115:3710-3715
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
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
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
Morgan, John T; Amaral, David G (2014) Comparative analysis of the dendritic organization of principal neurons in the lateral and central nuclei of the rhesus macaque and rat amygdala. J Comp Neurol 522:689-716
Morgan, John T; Barger, Nicole; Amaral, David G et al. (2014) Stereological study of amygdala glial populations in adolescents and adults with autism spectrum disorder. PLoS One 9:e110356
Chareyron, Loïc J; Lavenex, Pamela Banta; Amaral, David G et al. (2012) Postnatal development of the amygdala: A stereological study in macaque monkeys. J Comp Neurol 520:1965-84
Judson, Matthew C; Amaral, David G; Levitt, Pat (2011) Conserved subcortical and divergent cortical expression of proteins encoded by orthologs of the autism risk gene MET. Cereb Cortex 21:1613-26
Schumann, Cynthia Mills; Nordahl, Christine Wu (2011) Bridging the gap between MRI and postmortem research in autism. Brain Res 1380:175-86
Amaral, David G (2011) The promise and the pitfalls of autism research: an introductory note for new autism researchers. Brain Res 1380:3-9

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