[Abstract Title]. - Society for Neuroscience

Poster
242. Glial Neuronal Interactions: Glutamate and Calcium
Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm
Program#/Poster#: 242.22/J5
Topic: B.11.a. Synapses
Title: Molecular diffusion model of glutamate homeostasis in the nucleus accumbens to study
geometric configurations of perisynaptic glia and tortuosity
Authors: *S. PENDYAM 1 , A. MOHAN 1 , P. KALIVAS 2 , S. S. NAIR 1 ;
1 Univ. Missouri-Columbia, Columbia, MO; 2 Med. Univ. of South Carolina, Charleston, SC
Abstract: A typical chemical synapse has substantial morphological specialization to control
movement of substances that reflect special functional requirements. It is established that
synaptic geometry, molecules per vesicular release, neurotransmitter diffusion into the
perisynaptic space after a release, its binding to transporter and uptake via the glial sheaths, nonsynaptic
production (e.g., via cystine glutamate exchanger system located on the glial sheaths),
and inhibition of synaptic vesicular release due to negative feedback activation of receptors such
as the group II metabotropic autoreceptors contribute significantly to synaptic efficacy, plasticity
and homeostasis in the extracellular space.
Cellular adaptations in the reward circuitry of cocaine withdrawn rats are evident in the
prefrontal cortex - nucleus accumbal (PFC-NAc) glutamatergic projection. Two neuroplasticity
mechanisms observed are the functional down regulation of metabotropic glutamate receptors
and reduction in the basal extracellular glutamate level as a result of the diminished efficacy of
the glial cystine-glutamate exchange transporter. However, neither in vivo nor in vitro techniques
presently provide physiological information of the spatial and temporal glutamate profiles
needed to understand such mechanisms in the perisynaptic environment. Further, no
computational model exists that incorporates known physiological parameters to study such
mechanisms in cocaine pathologies.
A mathematical framework is proposed to study the mechanisms contributing to homeostasis in
the perisynaptic region surrounding a PFC-NAc synapse for control and cocaine cases.
Candidate glial geometries are proposed to characterize its role in regulating both synaptic and
non-synaptic glutamate uptake. The model can be used to predict homeostatic glutamate
concentrations at different locations for basal, reward seeking and cocaine pathologies. The
framework provides insight into the mechanisms of homeostasis, and enables identification of