Abstract

The nucleus accumbens is a focal point for integration of afferent information from the ventral tegmental area (VTA), amygdala, and hippocampus. This integration is accomplished through synaptic interactions of neurons containing a variety of neurotransmitters. The goal of the proposed research is to provide an ultrastructural basis for synaptic interactions between dopaminergic neurons of the ventral tegmental-accumbens pathways and other intrinsic neurons or afferents containing Gamma-aminobutyric acid (GABA) or one or more of the many neuropeptides identified in the VTA and n. accumbens. The dopaminergic neurons will be demonstrated by the immunocytochemical localization of the catecholamine synthesizing enzyme, tyrosine hydroxylase (TH) and the GABA-ergic neurons by the localization of glutamic acid decarboxylase (GAD). Antisera to these two enzymes and to neurotensin and neuropeptide Y will be localized by the peroxidase-antiperoxidase (PAP) technique and by the immunogold silver method to allow the simultaneous visualization of two antigens within single sections. The pathways containing the respective enzymatic or peptidergic markers will be examined by combining immunocytochemical labeling with anterograde or retrograde transport and with anterograde degeneration. The specific questions include: (a) What is the ultrastructural morphology of the dopaminergic neurons in the n. accumbens and VTA? (b) What are the synaptic associations between dopaminergic and GABA-ergic neurons? (c) What are the synaptic associations between the dopaminergic terminals and other afferents to the n. accumbens from the hippocampus and amygdala? and (d) What are the synaptic associations between the dopaminergic neurons and neurons containing neurotensin and neuropeptide Y? The results from these studies will extend our knowledge of neurotransmitter specific interactions of the dopaminergic neurons of the mesolimbic pathway. In addition, the findings may suggest imbalances of specific neurotransmitters which underlie neuropsychiatric disorders associated with the dopaminergic neurons.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH040342-03
Application #
3378427
Study Section
(BPNB)
Project Start
1985-09-01
Project End
1988-08-31
Budget Start
1987-09-01
Budget End
1988-08-31
Support Year
3
Fiscal Year
1987
Total Cost
Indirect Cost

  Institution

Name
Weill Medical College of Cornell University
Department
Type
Schools of Medicine
DUNS #
201373169
City
New York
State
NY
Country
United States
Zip Code
10065

  Publications

Glass, Michael J; Chan, June; Pickel, Virginia M (2017) Ultrastructural characterization of tumor necrosis factor alpha receptor type 1 distribution in the hypothalamic paraventricular nucleus of the mouse. Neuroscience 352:262-272
Gasser, Paul J; Hurley, Matthew M; Chan, June et al. (2017) Organic cation transporter 3 (OCT3) is localized to intracellular and surface membranes in select glial and neuronal cells within the basolateral amygdaloid complex of both rats and mice. Brain Struct Funct 222:1913-1928
Garzón, Miguel; Pickel, Virginia M (2016) Electron microscopic localization of M2-muscarinic receptors in cholinergic and noncholinergic neurons of the laterodorsal tegmental and pedunculopontine nuclei of the rat mesopontine tegmentum. J Comp Neurol 524:3084-103
Glass, Michael J; Wang, Gang; Coleman, Christal G et al. (2015) NMDA Receptor Plasticity in the Hypothalamic Paraventricular Nucleus Contributes to the Elevated Blood Pressure Produced by Angiotensin II. J Neurosci 35:9558-67
Gan, J O; Bowline, E; Lourenco, F S et al. (2014) Adolescent social isolation enhances the plasmalemmal density of NMDA NR1 subunits in dendritic spines of principal neurons in the basolateral amygdala of adult mice. Neuroscience 258:174-83
Garzón, Miguel; Pickel, Virginia M (2013) Somatodendritic targeting of M5 muscarinic receptor in the rat ventral tegmental area: implications for mesolimbic dopamine transmission. J Comp Neurol 521:2927-46
Garzón, M; Duffy, A M; Chan, J et al. (2013) Dopamine D? and acetylcholine ?7 nicotinic receptors have subcellular distributions favoring mediation of convergent signaling in the mouse ventral tegmental area. Neuroscience 252:126-43
Glass, Michael J; Robinson, Danielle C; Waters, Elizabeth et al. (2013) Deletion of the NMDA-NR1 receptor subunit gene in the mouse nucleus accumbens attenuates apomorphine-induced dopamine D1 receptor trafficking and acoustic startle behavior. Synapse 67:265-79
Fitzgerald, M L; Mackie, K; Pickel, V M (2013) The impact of adolescent social isolation on dopamine D2 and cannabinoid CB1 receptors in the adult rat prefrontal cortex. Neuroscience 235:40-50
Fitzgerald, Megan L; Shobin, Eli; Pickel, Virginia M (2012) Cannabinoid modulation of the dopaminergic circuitry: implications for limbic and striatal output. Prog Neuropsychopharmacol Biol Psychiatry 38:21-9

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