Transition to bistable behavior for the Nacc medium spiny neuron due to cocaine

1
Transition to bistable behavior for the Nacc
medium spiny neuron due to cocaine

• University of Missouri Columbia
• John Gall, Wes Smith, Satish Nair, Jyotsna Nair
• Medical University of South Carolina
• Peter Kalivas
• First Annual
• Biologically Accurate Modeling Meeting (BAMM)
• 2005

2
Objectives

• Develop reduced order models over different time
  scales (e.g., Gruber et al. 2002) using linear
  and nonlinear modeling techniques (Du and Nair
  2002).
• Bifurcation Analysis.
• Use systematic procedures to detect functional
  characteristics with focus on neuroplasticity,

3
Methods

• A biologically realistic computational model of
  the medium spiny neuron in the nucleus accumbens
  has been developed with focus on the
  glutamatergic PFC-Nacc pathway. The model
  considers neuroplasticity effects due to cocaine,
  including dendritic spine growth.
• A reduced order model considering one soma and
  one dendrite is considered for bistable behavior
• With analysis focusing on reinstatement,
  mechanisms of neuroplasticity affecting the
  change in membrane stability (bifurcation
  parameters) are considered.
• Examination of PFC-Nacc glutamatergic pathway
  via increasing AGS3, decreasing levels of
  extracellular glutamate, and decreasing iGluRs at
  the membrane, alterations in stability via degree
  of addiction.

4
Preliminary Results
Nullclines of the fast phase plane to study
neuroplasticity effects via analysis of
bifurcation.
5
Discussion and Conclusion

• A multi-level framework to incroporate known gene
  to membrane potential level dynamics, with the
  capability to integrate new data as they become
  available is taken.
• Mechanisms of bistability in the transition from
  normal to the chronic case are considered.
• A reduced order model of the Nucleus Accumbens
  medium spiny neuron for analytical study
• Bifurcation analysis to quantify effects of
  neuroplasticity