Clinical cortical stimulation and mapping studies led to the idea that the dysplastic neural networks are functionally integrated and atypically organized. However, the mechanisms for the establishment of aberrant neural networks and atypical brain organization await elucidation. In patient with cortical malformation, sensorimotor region are most frequent in finding polymicrogyri, and seizure onset commonly occurs with or near cortical areas for language and motor function. Motivated by these common clinical features of cortical dysplasia, we modified a neonatal freeze lesion animal model to interrogate how efferent activities in the normal motor cortex (M1), interacts with epileptogenic circuits located within ipsilateral malformed sensory cortex (S1). In our new mice model, optogenetic approaches will be combined with traditional focal freeze lesion, to study interactions between long-range motor cortical projections and local circuits within malformed sensory cortex. We hypothesize that 1) long-range connections from M1 onto interneurons are severely altered in malformed S1 cortex, leading to heightened ictogenesis and propagation. 2) Sensorimotor experiences during critical periods may selectively promote glutamatergic innervation of interneurons;thereby mitigate motor cortex induced seizure in S1. This exploratory grant is directed to provide the first proof of the involvement of long-range motor projection induced ictogenesis in S1, as well as its modulation by innate animal behavior. Understanding how glutamatergic synapses and epileptic activities are modulated by innate sensorimotor experiences during critical period will help development of stimulation-based physical therapy strategies might be used to mitigate or eradicate epilepsy pathology in humans.

Public Health Relevance

This exploratory grant is directed to understand how long-range epileptic networks are functionally integrated and atypically organized. Successful execution of this project will support the idea that epileptogenesis in malformed cortices can influence much wider areas via its long- range connections.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21NS084182-01
Application #
8569852
Study Section
Clinical Neuroplasticity and Neurotransmitters Study Section (CNNT)
Program Officer
Whittemore, Vicky R
Project Start
2013-09-01
Project End
2015-08-31
Budget Start
2013-09-01
Budget End
2014-08-31
Support Year
1
Fiscal Year
2013
Total Cost
$201,875
Indirect Cost
$51,875
Name
University of Wyoming
Department
Zoology
Type
Schools of Arts and Sciences
DUNS #
069690956
City
Laramie
State
WY
Country
United States
Zip Code
82071
Sun, Qian-Quan; Wang, Xinjun; Yang, Weiguo (2014) Laserspritzer: a simple method for optogenetic investigation with subcellular resolutions. PLoS One 9:e101600
Wang, Xinjun; Hooks, Bryan M; Sun, Qian-Quan (2014) Thorough GABAergic innervation of the entire axon initial segment revealed by an optogenetic 'laserspritzer'. J Physiol 592:4257-76