The Role of Inhibitory Interneurons in a Model od Developmental Epilepsy

Epilepsy, defined by recurrent seizures, is the one of the most prevalent neurological disorders worldwide (World Health Organization 2007). While many forms of epilepsy are well-controlled by anti-epileptogenic medications, a significant portion of patients have intractable, i.e. untreatable, seizures. The etiology of these seizures is varied, but a significant cause, particularly for patients with intractable epilepsy is developmental malformation. In these cases, an error or interruption during the development of the neocortex produces a structural alteration. Such patients may have other neurological problems, but seizures are the most common symptom. The neuronal mechanisms that link malformation and cortical hyperexcitability are not well understood. Here we have sought to examine potential mechanisms that result from microgyria, a malformation characterized by excessive numbers of small gyri.The presence of epileptiform activity indicates that the normal balance of excitation and inhibition has shifted . Two functions of inhibition within neocortex are to prevent spread of excitation, and to modulate the timing of surrounding excitation. Although seemingly contradictory, increasing some forms of inhibition can result in an increase in synchronous excitatory activity. We hypothesize that for certain malformation epilepsies, the inhibitory processes that control timing are increased, creating a hyper-synchronous cortex, while the inhibitory processes that control horizontal spread are decreased, allowing the propagation of such activity. Here we have examined the network effect of selectively modulating the inhibitory cells that control vertical or columnar cortical synchrony. This modulation is performed via activation of metabotropic glutamate receptors found on the vertically-projecting interneurons but not on those inhibitory cells that control horizontal spread of activity. Our results suggest that the network effect of activating these interneurons is altered in malformed, epileptogenic cortex.

Name thesis:degree_name

Master of Science

Level thesis:degree_level

Thesis

Discipline thesis:degree_discipline

Anatomy & Neurobiology

Year dc:date.available

2007

Author dc:creator

• Wolfgang, Patrick James

Contributors dc:contributor

• Dr. Kimberle Jacobs

• mGluR
• LTS
• Epilepsy
• interneurons
• Anatomy
• Medicine and Health Sciences
• Nervous System

Statement dc:rights

• © The Author

Identifier

https://scholarscompass.vcu.edu/etd/1145

OAI identifier oai:identifier

oai:scholarscompass.vcu.edu:etd-2144