The nucleus accumbens is a brain region with an important role in processing reward information and the selection of behaviors appropriate to the context. It has been proposed that one mechanism by which context guides response selection in the nucleus accumbens is via a synaptic interaction that has been characterized as a gating mechanism;hippocampal inputs are believed to be necessary for other inputs to drive action potential firing in the nucleus accumbens. Although the gating hypothesis has received further support from several studies, novel data indicate that the nucleus accumbens could disengage from its hippocampal inputs and follow prefrontal activity during epochs in which selection of a behavior is required. We proposed that the nucleus accumbens can behave a switchboard where response selection takes place by the interactions among multiple afferents. Here we will test whether the integration of information in the nucleus accumbens is critical for decision-making and selection of the appropriate behavioral response to a given context using multichannel recordings (simultaneously from the prefrontal cortex, hippocampus and nucleus accumbens) in two different operant tasks. Furthermore, we will explore the synaptic mechanisms underlying these interactions with in vivo intracellular recordings and whole cell recordings in accumbens slices, aimed at testing whether strong prefrontal afferent activation can attenuate the impact of hippocampal afferents and whether this interaction is dependent on local GABA or dopamine. Unveiling the cellular and synaptic processes responsible for response selection in the nucleus accumbens would advance our understanding of this critical function and pave the way to novel views on the pathophysiology of neuropsychiatric disorders, including schizophrenia, and perhaps eventually seek novel therapeutic approaches.

Public Health Relevance

This project will test whether the integration of information in the nucleus accumbens is critical for decision-making and selection of the appropriate behavioral response to a given context. In particular, we will assess the manner activity in the prefrontal cortex affects the influence exerted by the hippocampus on nucleus accumbens electrical activity and the behaviors that depend on it. Such integration of information in this critical brain region is important for understanding decision making and response selection and gaining an understanding of its mechanism will helps us develop better models to explain mental disorders.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH060131-14
Application #
8391753
Study Section
Neurobiology of Motivated Behavior Study Section (NMB)
Program Officer
Rossi, Andrew
Project Start
2000-12-13
Project End
2015-11-30
Budget Start
2012-12-01
Budget End
2013-11-30
Support Year
14
Fiscal Year
2013
Total Cost
$360,000
Indirect Cost
$120,000
Name
University of Maryland Baltimore
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
188435911
City
Baltimore
State
MD
Country
United States
Zip Code
21201
Calhoon, Gwendolyn G; O'Donnell, Patricio (2013) Closing the gate in the limbic striatum: prefrontal suppression of hippocampal and thalamic inputs. Neuron 78:181-90
Huppé-Gourgues, Frédéric; O'Donnell, Patricio (2012) D?-NMDA receptor interactions in the rat nucleus accumbens change during adolescence. Synapse 66:584-91
Huppe-Gourgues, Frederic; O'Donnell, Patricio (2012) Periadolescent changes of D(2) -AMPA interactions in the rat nucleus accumbens. Synapse 66:1-8
O'Donnell, Patricio (2011) Adolescent onset of cortical disinhibition in schizophrenia: insights from animal models. Schizophr Bull 37:484-92
Gruber, Aaron J; Hussain, Rifat J; O'Donnell, Patricio (2009) The nucleus accumbens: a switchboard for goal-directed behaviors. PLoS One 4:e5062
Gruber, Aaron J; Powell, Elizabeth M; O'Donnell, Patricio (2009) Cortically activated interneurons shape spatial aspects of cortico-accumbens processing. J Neurophysiol 101:1876-82
Gruber, Aaron J; O'Donnell, Patricio (2009) Bursting activation of prefrontal cortex drives sustained up states in nucleus accumbens spiny neurons in vivo. Synapse 63:173-80
Benoit-Marand, Marianne; O'Donnell, Patricio (2008) D2 dopamine modulation of corticoaccumbens synaptic responses changes during adolescence. Eur J Neurosci 27:1364-72
Benoit-Marand, Marianne; O'Donnell, Patricio (2008) Cortico-accumbens fiber stimulation does not induce dopamine release in the nucleus accumbens in vitro. Brain Struct Funct 213:177-82
Snyder-Keller, Abigail; Tseng, Kuei Y; Lyng, Gregory D et al. (2008) Afferent influences on striatal development in organotypic cocultures. Synapse 62:487-500

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