The specific neuronal circuitry that provides the foundation for sleep-related electrical activities in the brain is composed of reciprocal loops between interconnected areas of thalamus and neocortex. There is emerging evidence that this circuitry can be compromised in humans with generalized absence epilepsy, with the result that normal oscillatory sleep rhythms are converted into pathological epileptic activities. Within the thalamic half of the thalamocortical loop synaptic mechanisms promote both normal and abnormal oscillatory patterns. It is our hypothesis that regulation of synaptic strength within the thalamus is a key factor in determining whether normal are transformed into those associated with absence epilepsy. As a first step in testing this hypothesis, presynaptic control mechanisms in the thalamus will be investigated. These presynaptic mechanisms are expected to reduce the efficacy of synaptic transmission and may play a key role in the prevention of the neuronal activity associated with absence seizures. Gamma-aminobutyric acid (GABA receptor agonists and antagonists are powerful regulators of experimental absence seizures. The presynaptic actions of these compounds will be examined in the two principle types of neurons in rat somatosensory thalamus, the inhibitory cells within nucleus Reticularis thalami (nRt) and the excitatory relay neurons in the ventrobasal complex (VB). A microscope fitted with differential interference optics will be used to obtain high quality whole-cell voltage-clamp recordings form neurons visualized in thalamic slices maintained in vitro. The results of these studies may lead to new approaches in the treatment of human generalized epilepsy.
| Yackle, Kevin; Schwarz, Lindsay A; Kam, Kaiwen et al. (2017) Breathing control center neurons that promote arousal in mice. Science 355:1411-1415 |
| Birey, Fikri; Andersen, Jimena; Makinson, Christopher D et al. (2017) Assembly of functionally integrated human forebrain spheroids. Nature 545:54-59 |
| Makinson, Christopher D; Tanaka, Brian S; Sorokin, Jordan M et al. (2017) Regulation of Thalamic and Cortical Network Synchrony by Scn8a. Neuron 93:1165-1179.e6 |
| Sorokin, Jordan M; Davidson, Thomas J; Frechette, Eric et al. (2017) Bidirectional Control of Generalized Epilepsy Networks via Rapid Real-Time Switching of Firing Mode. Neuron 93:194-210 |
| Sorokin, Jordan M; Paz, Jeanne T; Huguenard, John R (2016) Absence seizure susceptibility correlates with pre-ictal ? oscillations. J Physiol Paris 110:372-381 |
| Ha, Huong; Huguenard, John (2016) Criminal Minds: Cav3.2 Channels Are the Culprits, but NMDAR Are the Co-Conspirators. Epilepsy Curr 16:36-8 |
| Pangratz-Fuehrer, Susanne; Sieghart, Werner; Rudolph, Uwe et al. (2016) Early postnatal switch in GABAA receptor ?-subunits in the reticular thalamic nucleus. J Neurophysiol 115:1183-95 |
| Fogerson, P Michelle; Huguenard, John R (2016) Tapping the Brakes: Cellular and Synaptic Mechanisms that Regulate Thalamic Oscillations. Neuron 92:687-704 |
| Brill, Julia; Mattis, Joanna; Deisseroth, Karl et al. (2016) LSPS/Optogenetics to Improve Synaptic Connectivity Mapping: Unmasking the Role of Basket Cell-Mediated Feedforward Inhibition. eNeuro 3: |
| Fogerson, P Michelle; Huguenard, John R (2016) Catching a wave. Elife 5: |
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