Computational and mathematical approaches will be used to study the mechanisms underlying synaptic regulation of midbrain dopaminergic neurons. These neurons are important in reward-mediated learning, drug addition, and motor control. The objective of the study is to produce a model of the DA neurons realistic enough to replicate the effect of synaptic inputs and pharmaceutics on these neurons so that the model could be used not only to elucidate the key currents, parameters, and mechanisms responsible for the generation and modulation of their electrical activity, but also to suggest therapeutic approaches for pathophysiologies in which DA neurons play a role.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
3R01NS037963-02S1
Application #
6091673
Study Section
Neurological Sciences Subcommittee 1 (NLS)
Program Officer
Oliver, Eugene J
Project Start
1998-02-09
Project End
2000-11-30
Budget Start
1998-12-01
Budget End
1999-11-30
Support Year
2
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Louisiana State University-University of New Orleans
Department
Psychology
Type
Schools of Arts and Sciences
DUNS #
City
New Orleans
State
LA
Country
United States
Zip Code
70148
Kuznetsova, Anna Y; Huertas, Marco A; Kuznetsov, Alexey S et al. (2010) Regulation of firing frequency in a computational model of a midbrain dopaminergic neuron. J Comput Neurosci 28:389-403
Migliore, Michele; Cannia, Claudio; Canavier, Carmen C (2008) A modeling study suggesting a possible pharmacological target to mitigate the effects of ethanol on reward-related dopaminergic signaling. J Neurophysiol 99:2703-7
Canavier, Carmen C; Oprisan, Sorinel A; Callaway, Joseph C et al. (2007) Computational model predicts a role for ERG current in repolarizing plateau potentials in dopamine neurons: implications for modulation of neuronal activity. J Neurophysiol 98:3006-22
Shepard, Paul D; Canavier, Carmen C; Levitan, Edwin S (2007) Ether-a-go-go-related gene potassium channels: what's all the buzz about? Schizophr Bull 33:1263-9
Canavier, C C; Landry, R S (2006) An increase in AMPA and a decrease in SK conductance increase burst firing by different mechanisms in a model of a dopamine neuron in vivo. J Neurophysiol 96:2549-63
Canavier, C C; Perla, S R; Shepard, P D (2004) Scaling of prediction error does not confirm chaotic dynamics underlying irregular firing using interspike intervals from midbrain dopamine neurons. Neuroscience 129:491-502
Komendantov, Alexander O; Komendantova, Olena G; Johnson, Steven W et al. (2004) A modeling study suggests complementary roles for GABAA and NMDA receptors and the SK channel in regulating the firing pattern in midbrain dopamine neurons. J Neurophysiol 91:346-57
Komendantov, Alexander O; Canavier, Carmen C (2002) Electrical coupling between model midbrain dopamine neurons: effects on firing pattern and synchrony. J Neurophysiol 87:1526-41
Lovejoy, L P; Shepard, P D; Canavier, C C (2001) Apamin-induced irregular firing in vitro and irregular single-spike firing observed in vivo in dopamine neurons is chaotic. Neuroscience 104:829-40
Canavier, C C (1999) Sodium dynamics underlying burst firing and putative mechanisms for the regulation of the firing pattern in midbrain dopamine neurons: a computational approach. J Comput Neurosci 6:49-69

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