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ABSTRACT: We introduce a method that uses optogenetic stimulation to evoke field potentials in brain slices prepared from transgenic mice expressing channelrhodopsin-2-YFP. Cortical slices in a recording chamber were stimulated with a 473nm blue laser via either a laser scanning photostimulation setup or by direct guidance of a fiber optic. Field potentials evoked by either of the two optogenetic stimulation methods had stable amplitude, consistent waveform, and similar components as events evoked with a conventional stimulating electrode. The amplitude of evoked excitatory postsynaptic potentials increased with increasing laser intensity or pulse duration. We further demonstrated that optogenetic stimulation can be used for the induction and monitoring of long-term depression. We conclude that this technique allows for efficient and reliable activation of field potentials in brain slice preparation, and will be useful for studying short and long term synaptic plasticity.
Journal of neuroscience methods 07/2012; 210(2):119-24. · 2.30 Impact Factor
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Joel M Brittain,
Djane B Duarte,
Sarah M Wilson,
Weiguo Zhu,
Carrie Ballard,
Philip L Johnson,
Naikui Liu, Wenhui Xiong,
Matthew S Ripsch,
Yuying Wang, [......],
Nickolay Brustovetsky,
Ru-Rong Ji,
Joyce H Hurley,
Xiaoming Jin,
Anantha Shekhar,
Xiao-Ming Xu,
Gerry S Oxford,
Michael R Vasko,
Fletcher A White,
Rajesh Khanna
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ABSTRACT: The use of N-type voltage-gated calcium channel (CaV2.2) blockers to treat pain is limited by many physiological side effects. Here we report that inflammatory and neuropathic hypersensitivity can be suppressed by inhibiting the binding of collapsin response mediator protein 2 (CRMP-2) to CaV2.2 and thereby reducing channel function. A peptide of CRMP-2 fused to the HIV transactivator of transcription (TAT) protein (TAT-CBD3) decreased neuropeptide release from sensory neurons and excitatory synaptic transmission in dorsal horn neurons, reduced meningeal blood flow, reduced nocifensive behavior induced by formalin injection or corneal capsaicin application and reversed neuropathic hypersensitivity produced by an antiretroviral drug. TAT-CBD3 was mildly anxiolytic without affecting memory retrieval, sensorimotor function or depression. At doses tenfold higher than that required to reduce hypersensitivity in vivo, TAT-CBD3 caused a transient episode of tail kinking and body contortion. By preventing CRMP-2-mediated enhancement of CaV2.2 function, TAT-CBD3 alleviated inflammatory and neuropathic hypersensitivity, an approach that may prove useful in managing chronic pain.
Nature medicine 06/2011; 17(7):822-9. · 27.14 Impact Factor
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ABSTRACT: Partially isolated cortex ("undercut") is an animal model of posttraumatic epileptogenesis. The surgical procedure involves cutting through the sensorimotor cortex and the underneath white matter (undercut) so that a specific region of the cerebral cortex is largely isolated from the neighboring cortex and subcortical regions(1-3). After a latency of two or more weeks following the surgery, epileptiform discharges can be recorded in brain slices from rodents(1); and electrical or behavior seizures can be observed in vivo from other species such as cat and monkey(4-6). This well established animal model is efficient to generate and mimics several important characteristics of traumatic brain injury. However, it is technically challenging attempting to make precise cortical lesions in the small rodent brain with a free hand. Based on the procedure initially established in Dr. David Prince's lab at the Stanford University(1), here we present an improved technique to perform a surgery for the preparation of this model in mice and rats. We demonstrate how to make a simple surgical device and use it to gain a better control of cutting depth and angle to generate more precise and consistent results. The device is easy to make, and the procedure is quick to learn. The generation of this animal model provides an efficient system for study on the mechanisms of posttraumatic epileptogenesis.
Journal of Visualized Experiments 01/2011;
