QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, October 5, 2005, 25(40):9080-9095; doi:10.1523/JNEUROSCI.2220-05.2005

This Article Full Text Full Text (PDF) Supplemental data Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (14) Citing Articles via Google Scholar Google Scholar Articles by Wolf, J. A. Articles by Finkel, L. H. Search for Related Content PubMed PubMed Citation Articles by Wolf, J. A. Articles by Finkel, L. H.

 Previous Article  |  Next Article 

Behavioral/Systems/Cognitive
NMDA/AMPA Ratio Impacts State Transitions and Entrainment to Oscillations in a Computational Model of the Nucleus Accumbens Medium Spiny Projection Neuron

John A. Wolf,¹ Jason T. Moyer,² Maciej T. Lazarewicz,² Diego Contreras,¹ Marianne Benoit-Marand,³ Patricio O'Donnell,³ and Leif H. Finkel²

Departments of ¹Neuroscience and ²Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania 19104, and ³Center for Neuropharmacology and Neuroscience, Albany Medical College, Albany, New York 12208

We describe a computational model of the principal cell in the nucleus accumbens (NAcb), the medium spiny projection (MSP) neuron. The model neuron, constructed in NEURON, includes all of the known ionic currents in these cells and receives synaptic input from simulated spike trains via NMDA, AMPA, and GABA_A receptors. After tuning the model by adjusting maximal current conductances in each compartment, the model cell closely matched whole-cell recordings from an adult rat NAcb slice preparation. Synaptic inputs in the range of 1000-1300 Hz are required to maintain an "up" state in the model. Cell firing in the model required concurrent depolarization of several dendritic branches, which responded independently to afferent input. Depolarization from action potentials traveled to the tips of the dendritic branches and increased Ca²⁺ influx through voltage-gated Ca²⁺ channels. As NMDA/AMPA current ratios were increased, the membrane showed an increase in hysteresis of "up" and "down" state dwell times, but intrinsic bistability was not observed. The number of oscillatory inputs required to entrain the model cell was determined to be 20% of the "up" state inputs. Altering the NMDA/AMPA ratio had a profound effect on processing of afferent input, including the ability to entrain to oscillations in afferent input in the theta range (4-12 Hz). These results suggest that afferent information integration by the NAcb MSP cell may be compromised by pathology in which the NMDA current is altered or modulated, as has been proposed in both schizophrenia and addiction.

Key words: addiction; basal ganglia; schizophrenia; MSP; theta; oscillation; NMDA/AMPA ratio; computational model; ventral striatum; hysteresis; bistability

---

Received Feb 10, 2005; revised July 15, 2005; accepted August 3, 2005.

This article has been cited by other articles:

				Y. H. Huang, Y. Lin, T. E. Brown, M.-H. Han, D. B. Saal, R. L. Neve, R. S. Zukin, B. A. Sorg, E. J. Nestler, R. C. Malenka, et al. CREB Modulates the Functional Output of Nucleus Accumbens Neurons: A CRITICAL ROLE OF N-METHYL-D-ASPARTATE GLUTAMATE RECEPTOR (NMDAR) RECEPTORS J. Biol. Chem., February 1, 2008; 283(5): 2751 - 2760. [Abstract] [Full Text] [PDF]

				K. K. Ade, M. J. Janssen, P. I. Ortinski, and S. Vicini Differential Tonic GABA Conductances in Striatal Medium Spiny Neurons J. Neurosci., January 30, 2008; 28(5): 1185 - 1197. [Abstract] [Full Text] [PDF]

				A. J. Milnerwood and L. A. Raymond Corticostriatal synaptic function in mouse models of Huntington's disease: early effects of huntingtin repeat length and protein load J. Physiol., December 15, 2007; 585(3): 817 - 831. [Abstract] [Full Text] [PDF]

				J. T. Moyer, J. A. Wolf, and L. H. Finkel Effects of Dopaminergic Modulation on the Integrative Properties of the Ventral Striatal Medium Spiny Neuron J Neurophysiol, December 1, 2007; 98(6): 3731 - 3748. [Abstract] [Full Text] [PDF]

				Y. Tu, S. Kroener, K. Abernathy, C. Lapish, J. Seamans, L. J. Chandler, and J. J. Woodward Ethanol Inhibits Persistent Activity in Prefrontal Cortical Neurons J. Neurosci., April 25, 2007; 27(17): 4765 - 4775. [Abstract] [Full Text] [PDF]

				A. Kepecs and S. Raghavachari Gating Information by Two-State Membrane Potential Fluctuations J Neurophysiol, April 1, 2007; 97(4): 3015 - 3023. [Abstract] [Full Text] [PDF]

				M. D'Ascenzo, T. Fellin, M. Terunuma, R. Revilla-Sanchez, D. F. Meaney, Y. P. Auberson, S. J. Moss, and P. G. Haydon mGluR5 stimulates gliotransmission in the nucleus accumbens PNAS, February 6, 2007; 104(6): 1995 - 2000. [Abstract] [Full Text] [PDF]

				F. Kasanetz, L. A. Riquelme, P. O'Donnell, and M. G. Murer Turning off cortical ensembles stops striatal Up states and elicits phase perturbations in cortical and striatal slow oscillations in rat in vivo J. Physiol., November 15, 2006; 577(1): 97 - 113. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help