1,721,289 research outputs found
Chemogenetic seizure suppression in a mouse model for temporal lobe epilepsy : 'pumping up the jam'?
No full textExploration of the effects of vagus nerve stimulation on tumor growth in a preclinical model for glioma-related epilepsy and identification of a marker for effective stimulation
No full textOptogenetic modulation of hippocampal excitability and seizures
No full textOptogenetics involves the directed expression of light-sensitive proteins (opsins) in the neurons of interest, which allows selective modulation of brain regions with a high degree of spatiotemporal precision. Among the various opsins currently available, ion-conducting opsins are frequently used to excite or inhibit neurons. Activation of cation-conducting channel opsins, such as ChR2, can excite neurons, whereas activation of anion-conducting pump opsins can inhibit neurons. However, the use of opsin pumps, such as NpHR can pose several limitations for in vivo experimentation, such as changes in ionic homeostasis. GtACR2 is a naturally occurring blue light-sensitive anion channel that can overcome the limitations of opsin pumps and inhibit neurons by shunting the membrane depolarization. These features of GtACR2 make it a desirable tool to modulate neuronal excitability in vivo and to test its and to test its applicability as an experimental treatment strategy for suppression of aberrant electrophysiological activity known as ‘seizures’.
In this study, we first evaluated the effects of GtACR2 activation on the excitability of hippocampal CA1 neurons in anesthetized rats in vivo. Next, the illumination parameters required to activate GtACR2 were optimized, as light absorption results in local heating of the brain and can affect the physiology of the neurons at illuminated site. Finally, the potency of GtACR2 in suppressing seizures in the dentate gyrus of anesthetized rats was tested.
The results presented in this thesis demonstrated that GtACR2 is a potent optogenetic tool for inhibiting the population of neurons in vivo. Owing to its high photosensitivity, it can be activated with relatively low LPDs, thereby minimizing the inadvertent heating and confounding effects on neurophysiology. In addition, in the animal model used, GtACR2 activation resulted in a focal reduction in seizure amplitude at the illuminated site, suggesting that these opsins are suitable for suppressing aberrant activities such as seizures. However, this also highlights the limitation of optogenetics i.e., modulation of brain regions is limited to smaller volume, and currently these tools are more suited for analytical researc
Exploring the therapeutic potential of vagus nerve stimulation in multiple sclerosis : insights from preclinical models
No full textOptimization of chemogenetic modulation of the locus coeruleus in rat to study its relation to hippocampal excitability
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Temperature as a confounder on vagus nerve stimulation induced brain excitability modulation in rats
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Optical modulation of neuronal excitability using a novel photocaged adenosine A1 receptor agonist and its application in an ex vivo seizure model
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