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The role of dopamine in long-term plasticity in the rat prefrontal cortex: a computational model

Denis Sheynikhovich1*, Satoru Otani2 and Angelo Arleo3
  • 1 Lab. of Neurobiology of Adaptive Processes , France
  • 2 Univ Paris 6 , INSERM U952, CNRS-UMR7224 , France
  • 3 Univ Paris 6 , CNRS-UMR7102, France

The prefrontal cortex (PFC) is thought to mediate executive functions, including strategic organization of behavior (Fuster, 1995). These functions rely on long-term plasticity within the PFC (Touzani et al., 2007). Dopamine (DA) input to the PFC has been shown to modulate the magnitude and direction (i.e. potentiation, LTP; or depression, LTD) of long-term plasticity induced by tetanic stimulation in vitro (Kolomiets et al., 2009; Huang et al., 2004). Moreover, the DA action is different depending on whether tonic (background) or phasic (stimulation-induced) DA levels are manipulated. Whereas a fair amount of theoretical work addresses short-term DA action on the level of single PFC neurons and its importance for working memory, no theoretical models address the role of DA for long-term plasticity in the PFC. The present work attempts to fill this gap by proposing a computational model of induction and maintenance of LTP and LTD in the PFC under the influence of DA. We use a Hodgkin-Huxley-type computational model of a single PFC layer V pyramidal cell and we study neuronal properties that may be responsible for the changes in synaptic efficacy following tetanic stimulation in the presence of DA. We use a variant of Tag-Trigger-Consolidation framework (Clopath et al., 2008) as a model for LTP and LTD induction and maintenance. Distinct properties of our model are a DA-dose-dependent switch from LTD to LTP during induction, and an inverted-U-shape dependence of protein synthesis threshold on the level of background DA. Protein synthesis is responsible for maintenance and late phase of LTP/LTD in the model. The model has been tested by stimulating the simulated neuron with spike trains of different duration under different doses of DA and has been found to reproduce well the results of the in vitro studies. Our simulations suggest that in order to comply with the in vitro data, prefrontal synapses must contain a protein that is slowly (on the timescale of minutes) activated in the presence of DA in a dose-dependent manner. The activation value at the time of the stimulation, and the internal calcium level determine the direction of plasticity at prefrontal synapses in the model. The calcium level during stimulation is dependent on the strength of the stimulation mainly via the activation of N-methyl-D-aspartate receptors (LTP) or metabotropic glutamate receptors (LTD). We propose several candidate molecules for the putative DA-activated protein. More generally our results support the hypothesis that phasic release of endogenous DA is necessary for the induction of long-term changes in synaptic efficacy, while the concentration of tonic DA determines the direction (i.e. LTP or LTD) of these changes (Kolomiets et al., 2009).

References

1. Clopath C, Ziegler L, Vasilaki E, Busing L, Gerstner W (2008) PLoS Comput Biol. 4(12):e1000248 Fuster JM (1995) Boston: The MIT Press. Huang YY, Simpson E, Kellendonk C, Kandel ER (2004) Proc Natl Acad Sci USA. 101:3236-3241 Kolomiets B, Marzo A, Caboche J, Vanhoutte P, Otani S (2009) Cereb Cortex (E-pub ahead of print) Touzani K, Puthanveettil SV, Kandel ER (2007) Proc Natl Acad Sci USA. 104:5632-5637

Conference: Computational and Systems Neuroscience 2010, Salt Lake City, UT, United States, 25 Feb - 2 Mar, 2010.

Presentation Type: Poster Presentation

Topic: Poster session II

Citation: Sheynikhovich D, Otani S and Arleo A (2010). The role of dopamine in long-term plasticity in the rat prefrontal cortex: a computational model. Front. Neurosci. Conference Abstract: Computational and Systems Neuroscience 2010. doi: 10.3389/conf.fnins.2010.03.00230

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Received: 04 Mar 2010; Published Online: 04 Mar 2010.

* Correspondence: Denis Sheynikhovich, Lab. of Neurobiology of Adaptive Processes, Paris, France, denis.sheynikhovich@upmc.fr