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Dynamics of Dressed Neurons: Modeling the Neural-Glial Circuit and Exploring its Normal and Pathological Implications

Nadkarni, Suhita

Abstract Details

2005, Doctor of Philosophy (PhD), Ohio University, Physics (Arts and Sciences).

It is now established that glial cells are active partners to neurons in the nervous system. Astrocytes, a subtype of glial cell, through characteristic calcium based excitability are able to integrate the activity of neurons and thereby modulate their normal function. Quantifiable coupling schemes were developed to incorporate the role of astrocytes in neuronal dynamics. The coupling mechanism between the two cells is dynamic, bidirectional and is based on experimental data. It takes place at two distinct time scales, with the calcium activity in astrocytes occurring in seconds while the electrical activity in neurons in milliseconds. Because of the extent of their influence on neuronal dynamics astrocytes can also be thought to play a crucial role in certain neurological disorders. Basic, yet physiologically relevant circuits were constructed to explore the consequences of aberrations in neuron astrocyte coupling. Our results suggest that stronger coupling between the two cells, which takes the form of upregulation of metabotropic glutamate receptors (mGluRs) by a factor of few tens in astrocytes in our model, makes the neuron hyperexcitable and leads to self sustained (seizure like) oscillations. This prediction is consistent with the experimental observation of 20-30 times more mGluRs seen on astrocytes of epileptic tissue. Further, inhibition by interneurons in the hippocampus is an essential mechanism. The complex dichotomy of excitation and inhibition defines the normal dynamics of the brain. The inhibitive action of interneurons is also thought to provide a vital first line of defense in pathological conditions like epilepsy. The effect of local inhibition on a hyperexcitable system with enhanced astrocytic coupling was examined and it was inferred that local inhibition is unlikely to remedy the hyperexcitable system. Under normal physiological conditions astrocytes are seen to strengthen spontaneous activity of neurons, a mechanism said to be involved in plasticity and learning. Our model is able to quantitatively mimic this pattern of marked increase of spontaneous activity due to the astrocyte. Synaptic transmission is the central pathway through which information processing is carried out. The role of astrocytes in potentiating synaptic transmission was studied. The simulations carried out are a pointer to astrocytes, as playing a role in enhancing signal transmission.

Peter Jung (Advisor)
141 p.

Recommended Citations

Citations

  • Nadkarni, S. (2005). Dynamics of Dressed Neurons: Modeling the Neural-Glial Circuit and Exploring its Normal and Pathological Implications [Doctoral dissertation, Ohio University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1125689320

    APA Style (7th edition)

  • Nadkarni, Suhita. Dynamics of Dressed Neurons: Modeling the Neural-Glial Circuit and Exploring its Normal and Pathological Implications. 2005. Ohio University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1125689320.

    MLA Style (8th edition)

  • Nadkarni, Suhita. "Dynamics of Dressed Neurons: Modeling the Neural-Glial Circuit and Exploring its Normal and Pathological Implications." Doctoral dissertation, Ohio University, 2005. http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1125689320

    Chicago Manual of Style (17th edition)