Asrican Brent

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  • Article
    Persistent accumulation of calcium/calmodulin-dependent protein kinase II in dendritic spines after induction of NMDA receptor-dependent chemical long-term potentiation
    (Society for Neuroscience, 2004-10-20) Otmakhov, Nikolai ; Tao-Cheng, Jung-Hwa ; Carpenter, Stephen ; Asrican, Brent ; Dosemeci, Ayse ; Reese, Thomas S. ; Lisman, John E.
    Calcium/calmodulin-dependent protein kinase II (CaMKII) is a leading candidate for a synaptic memory molecule because it is persistently activated after long-term potentiation (LTP) induction and because mutations that block this persistent activity prevent LTP and learning. Previous work showed that synaptic stimulation causes a rapidly reversible translocation of CaMKII to the synaptic region. We have now measured green fluorescent protein (GFP)-CaMKIIα translocation into synaptic spines during NMDA receptor-dependent chemical LTP (cLTP) and find that under these conditions, translocation is persistent. Using red fluorescent protein as a cell morphology marker, we found that there are two components of the persistent accumulation. cLTP produces a persistent increase in spine volume, and some of the increase in GFP-CaMKIIα is secondary to this volume change. In addition, cLTP results in a dramatic increase in the bound fraction of GFP-CaMKIIα in spines. To further study the bound pool, immunogold electron microscopy was used to measure CaMKIIα in the postsynaptic density (PSD), an important regulator of synaptic function. cLTP produced a persistent increase in the PSD-associated pool of CaMKIIα. These results are consistent with the hypothesis that CaMKIIα accumulation at synapses is a memory trace of past synaptic activity.
  • Article
    Optogenetic mapping of cerebellar inhibitory circuitry reveals spatially biased coordination of interneurons via electrical synapses
    (Cell Press, 2014-05-22) Kim, Jinsook ; Lee, Soojung ; Tsuda, Sachiko ; Zhang, Xuying ; Asrican, Brent ; Gloss, Bernd ; Feng, Guoping ; Augustine, George J.
    We used high-speed optogenetic mapping technology to examine the spatial organization of local inhibitory circuits formed by cerebellar interneurons. Transgenic mice expressing channelrhodopsin-2 exclusively in molecular layer interneurons allowed us to focally photostimulate these neurons, while measuring resulting responses in postsynaptic Purkinje cells. This approach revealed that interneurons converge upon Purkinje cells over a broad area and that at least seven interneurons form functional synapses with a single Purkinje cell. The number of converging interneurons was reduced by treatment with gap junction blockers, revealing that electrical synapses between interneurons contribute substantially to the spatial convergence. Remarkably, gap junction blockers affected convergence in sagittal slices, but not in coronal slices, indicating a sagittal bias in electrical coupling between interneurons. We conclude that electrical synapse networks spatially coordinate interneurons in the cerebellum and may also serve this function in other brain regions.
  • Article
    Next-generation transgenic mice for optogenetic analysis of neural circuits
    (Frontiers Media, 2013-11-26) Asrican, Brent ; Augustine, George J. ; Berglund, Ken ; Chen, Susu ; Chow, Nick ; Deisseroth, Karl ; Feng, Guoping ; Gloss, Bernd ; Hira, Riichiro ; Hoffmann, Carolin ; Kasai, Haruo ; Katarya, Malvika ; Kim, Jinsook ; Kudolo, John ; Lee, Li Ming ; Lo, Shun Qiang ; Mancuso, James ; Matsuzaki, Masanori ; Nakajima, Ryuichi ; Qiu, Li ; Tan, Gregory ; Tang, Yanxia ; Ting, Jonathan T. ; Tsuda, Sachiko ; Wen, Lei ; Zhang, Xuying ; Zhao, Shengli
    Here we characterize several new lines of transgenic mice useful for optogenetic analysis of brain circuit function. These mice express optogenetic probes, such as enhanced halorhodopsin or several different versions of channelrhodopsins, behind various neuron-specific promoters. These mice permit photoinhibition or photostimulation both in vitro and in vivo. Our results also reveal the important influence of fluorescent tags on optogenetic probe expression and function in transgenic mice.