The aim of this project is to study why rapid eye movement (REM) sleep is an anticonvulsant state and to test whether stimulation of REM-promoting brain regions prevents seizures. Experiments will focus on the pedunculopontine nucleus (PPT), a midbrain cholinergic region that densely innervates the thalamus. Electrophysiological and optical recordings will be done in the thalamus, neocortex, and hippocampus in healthy and epileptic rats. The central motivating hypothesis is that REM is a neuroprotective state due to the wide-spread cortical asynchrony observed in this state which arises, in part, due to cholinergic signaling in the thalamus.
Specific Aim 1. 1 will test how electrical stimulation of the PPT affects acetylcholine binding in the thalamus and the firing patterns of cortical and thalamic neurons in healthy rats. These experiments will establish a database of how the brain reacts to different kinds of stimulations so that if a therapeutic protocol is discovered, its neurophysiological mechanism of action can be better understood.
Specific Aim 1. 2 will test whether these same stimulation protocols change the seizure threshold in the kindling model of epilepsy. I hypothesize that those stimulations that induce strong thalamic acetylcholine binding will also be those that induce cortical asynchrony and most effectively suppress seizure spread in the evoked kindling model.
Specific Aim 2 will then test whether electrical stimulation of the PPT is effective in suppressing seizures in a chronic epilepsy model induced by intra-hippocampal kainic acid injection. Seizures will be predicted online, and stimulation of the PPT will be given when seizures are likely. These experiments will further our understanding of the link between seizures and sleep and will guide future clinical studies to assess whether REM promoting brain regions should be targeted in patients suffering from epilepsy.
|Campbell, Richard A; Gorman, Stephanie A; Thoma, Robert J et al. (2018) Risk of Concussion During Sports Versus Physical Education Among New Mexico Middle and High School Students. Am J Public Health 108:93-95|
|Trofimov, Alexey O; Kalentiev, George; Karelsky, Michael et al. (2018) Cerebral Hemodynamics After Transcranial Direct Current Stimulation (tDCS) in Patients with Consequences of Traumatic Brain Injury. Adv Exp Med Biol 1072:59-62|
|Bragina, O A; Lara, D A; Nemoto, E M et al. (2018) Increases in Microvascular Perfusion and Tissue Oxygenation via Vasodilatation After Anodal Transcranial Direct Current Stimulation in the Healthy and Traumatized Mouse Brain. Adv Exp Med Biol 1072:27-31|
|Bikson, Marom; Brunoni, Andre R; Charvet, Leigh E et al. (2018) Rigor and reproducibility in research with transcranial electrical stimulation: An NIMH-sponsored workshop. Brain Stimul 11:465-480|
|MacQueen, David A; Minassian, Arpi; Kenton, Johnny A et al. (2018) Amphetamine improves mouse and human attention in the 5-choice continuous performance test. Neuropharmacology 138:87-96|
|Gustus, Kymberly C; Li, Lu; Chander, Praveen et al. (2018) Genetic inactivation of synaptosomal-associated protein 25 (SNAP-25) in adult hippocampal neural progenitors impairs pattern discrimination learning but not survival or structural maturation of newborn dentate granule cells. Hippocampus 28:735-744|
|Dobrzeniecki, Michael; Trofimov, Alex; Bragin, Denis E (2018) Cerebral Arterial Compliance in Traumatic Brain Injury. Acta Neurochir Suppl 126:21-24|
|Mayer, Andrew R; Kaushal, Mayank; Dodd, Andrew B et al. (2018) Advanced biomarkers of pediatric mild traumatic brain injury: Progress and perils. Neurosci Biobehav Rev 94:149-165|
|Bragin, Denis E; Bragina, Olga A; Hagberg, Sean et al. (2018) Pulsed Electromagnetic Field (PEMF) Mitigates High Intracranial Pressure (ICP) Induced Microvascular Shunting (MVS) in Rats. Acta Neurochir Suppl 126:93-95|
|Bragin, Denis E; Statom, Gloria L; Nemoto, Edwin M (2018) Induced Dynamic Intracranial Pressure and Cerebrovascular Reactivity Assessment of Cerebrovascular Autoregulation After Traumatic Brain Injury with High Intracranial Pressure in Rats. Acta Neurochir Suppl 126:309-312|
Showing the most recent 10 out of 46 publications