The Section on Neuroanatomy studies the functional organization of the cerebral cortex and basal ganglia. Connections between functionally defined cortical areas provide neuroanatomical substrates of cognition, including purposive movement. We suggest that these cortico-cortical connections are represented in the organization of cortical inputs to the striatum, the basal ganglia target of the cortex. How the striatum processes this input, which is fed back to the cortex, is the subject of our work. These studies use neuroanatomical techniques. including axonal tract tracing. immunohistochemistry, and in situ hybridization histochemistry to examine cerebral cortical and basal ganglia connections, specifically the organization of cortical inputs to the striatum, and to characterize striatal output neurons in terms of their connections and expression of neurotransmitter receptors, signal transduction systems, and neurotransmitters/ peptides. Processing of cortical inputs to the striatum is studied with pharmacologic manipulations of dopamine and acetylcholine receptor-mediated gene regulation of connectionally and neurochemically defined striatal iatal neurons with quantitative in situ hybridization. As a working hypothesis, it is proposed that the basal ganglia process cortical inputs to either facilitate or disfacilitate feedback to the frontal cortex. This is thought to involve a balance between antagonistic striatal output pathways, which we have shown to be oppositely affected by dopamine. Our studies have provided insights into the cellular mechanisms involved in the disruption of the normal balance between these pathways that occurs in Parkinson's disease. Moreover, it is suggested that disordered cognition in schizophrenia may be related to corticocortical and corticostriatal dysfunction.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Intramural Research (Z01)
Project #
1Z01MH002497-04
Application #
3781425
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
4
Fiscal Year
1993
Total Cost
Indirect Cost
Name
U.S. National Institute of Mental Health
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Gerfen, Charles R; Economo, Michael N; Chandrashekar, Jayaram (2018) Long distance projections of cortical pyramidal neurons. J Neurosci Res 96:1467-1475
Ruiz, Sarah K; Harris, Susan J; Martinez, Pedro et al. (2018) Young adult's attachment style as a partial mediator between maternal functioning and young adult offsprings' functioning. J Affect Disord 232:393-399
Gerfen, Charles R; Paletzki, Ronald; Heintz, Nathaniel (2013) GENSAT BAC cre-recombinase driver lines to study the functional organization of cerebral cortical and basal ganglia circuits. Neuron 80:1368-83
Gerfen, Charles R; Paletzki, Ronald; Worley, Paul (2008) Differences between dorsal and ventral striatum in Drd1a dopamine receptor coupling of dopamine- and cAMP-regulated phosphoprotein-32 to activation of extracellular signal-regulated kinase. J Neurosci 28:7113-20
Szklarczyk, Arek; Oyler, George; McKay, Ron et al. (2007) Cleavage of neuronal synaptosomal-associated protein of 25 kDa by exogenous matrix metalloproteinase-7. J Neurochem 102:1256-63
Szklarczyk, A; Conant, K; Owens, D F et al. (2007) Matrix metalloproteinase-7 modulates synaptic vesicle recycling and induces atrophy of neuronal synapses. Neuroscience 149:87-98
Manning-Bog, Amy B; Caudle, W Michael; Perez, Xiomara A et al. (2007) Increased vulnerability of nigrostriatal terminals in DJ-1-deficient mice is mediated by the dopamine transporter. Neurobiol Dis 27:141-50
Kim, D S; Palmiter, R D; Cummins, A et al. (2006) Reversal of supersensitive striatal dopamine D1 receptor signaling and extracellular signal-regulated kinase activity in dopamine-deficient mice. Neuroscience 137:1381-8
Brown, Pierre; Gerfen, Charles R (2006) Plasticity within striatal direct pathway neurons after neonatal dopamine depletion is mediated through a novel functional coupling of serotonin 5-HT2 receptors to the ERK 1/2 map kinase pathway. J Comp Neurol 498:415-30
Gerfen, Charles R (2006) Indirect-pathway neurons lose their spines in Parkinson disease. Nat Neurosci 9:157-8

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