עבודה זו נתמכה על ידי קרן מחקר גרמני (DFG RE 2740/3-1). אנו מודים פרנק Huethe, תומאס גינתר לייצור שבאתר מלון טס מחוייט הקמה DC-מגרה.

<ol>
	<li>Bikson, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Safety+of+Transcranial+Direct+Current+Stimulation:+Evidence+Based+Update+2016.">Safety of Transcranial Direct Current Stimulation: Evidence Based Update 2016.</a> Brain Stimul. 9 (5), 641-661 (2016).</li><li>Bindman, L. J., Lippold, O. C., Redfearn, J. W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+action+of+brief+polarizing+currents+on+the+cerebral+cortex+of+the+rat+(1)+during+current+flow+and+(2)+in+the+production+of+long-lasting+after-effects.">The action of brief polarizing currents on the cerebral cortex of the rat (1) during current flow and (2) in the production of long-lasting after-effects.</a> J Physiol. 172, 369-382 (1964).</li><li>Gartside, I. B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Mechanisms+of+sustained+increases+of+firing+rate+of+neurones+in+the+rat+cerebral+cortex+after+polarization:+role+of+protein+synthesis.">Mechanisms of sustained increases of firing rate of neurones in the rat cerebral cortex after polarization: role of protein synthesis.</a> Nature. 220 (5165), 382-383 (1968).</li><li>Purpura, D. P., McMurtry, J. G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Intracellular+activities+and+potential+changes+during+polarization+of+motor+cortex.">Intracellular activities and potential changes during polarization of motor cortex.</a> Neurophysiol. 28 (1), 166-185 (1965).</li><li>Nitsche, M., Paulus, W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Excitability+changes+induced+in+the+human+motor+cortex+by+weak+transcranial+direct+current+stimulation.">Excitability changes induced in the human motor cortex by weak transcranial direct current stimulation.</a> J Physiol. 527 (Pt 3), 633-639 (2000).</li><li>Nitsche, M. A., Paulus, W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Sustained+excitability+elevations+induced+by+transcranial+DC+motor+cortex+stimulation+in+humans.">Sustained excitability elevations induced by transcranial DC motor cortex stimulation in humans.</a> Neurology. 57 (10), 1899-1901 (2001).</li><li>Cambiaghi, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Brain+transcranial+direct+current+stimulation+modulates+motor+excitability+in+mice.">Brain transcranial direct current stimulation modulates motor excitability in mice.</a> Eur J Neuro. 31 (4), 704-709 (2010).</li><li>Fritsch, B., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Direct+current+stimulation+promotes+BDNF-dependent+synaptic+plasticity:+potential+implications+for+motor+learning.">Direct current stimulation promotes BDNF-dependent synaptic plasticity: potential implications for motor learning.</a> Neuron. 66 (2), 198-204 (2010).</li><li>Ranieri, F., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Modulation+of+LTP+at+rat+hippocampal+CA3-CA1+synapses+by+direct+current+stimulation.">Modulation of LTP at rat hippocampal CA3-CA1 synapses by direct current stimulation.</a> J Neurophysiol. 107 (7), 1868-1880 (2012).</li><li>Kronberg, G., Bridi, M., Abel, T., Bikson, M., Parra, L. C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Direct+Current+Stimulation+Modulates+LTP+and+LTD:+Activity+Dependence+and+Dendritic+Effects.">Direct Current Stimulation Modulates LTP and LTD: Activity Dependence and Dendritic Effects.</a> Brain Stimul. 10 (November), 51-58 (2016).</li><li>Sun, Y., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Direct+current+stimulation+induces+mGluR5-dependent+neocortical+plasticity.">Direct current stimulation induces mGluR5-dependent neocortical plasticity.</a> Ann Neurol. 80 (2), 233-246 (2016).</li><li>Podda, M. V., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Anodal+transcranial+direct+current+stimulation+boosts+synaptic+plasticity+and+memory+in+mice+via+epigenetic+regulation+of+Bdnf+expression.">Anodal transcranial direct current stimulation boosts synaptic plasticity and memory in mice via epigenetic regulation of Bdnf expression.</a> Sci Rep. 6, 22180 (2016).</li><li>Reis, J., Fritsch, B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Modulation+of+motor+performance+and+motor+learning+by+transcranial+direct+current+stimulation.">Modulation of motor performance and motor learning by transcranial direct current stimulation.</a> Curr opin Neurology. 24 (6), 590-596 (2011).</li><li>Buch, E. R., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Effects+of+tDCS+on+motor+learning+and+memory+formation+a+consensus+and+critical+position+paper.">Effects of tDCS on motor learning and memory formation a consensus and critical position paper.</a> Clin Neurophysiol. 128 (4), 589-603 (2017).</li><li>Reis, J., Fischer, J. T., Prichard, G., Weiller, C., Cohen, L. G., Fritsch, B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Time-+but+not+sleep-dependent+consolidation+of+tDCS-enhanced+visuomotor+skills.">Time- but not sleep-dependent consolidation of tDCS-enhanced visuomotor skills.</a> Cerebral cortex. 25 (1), 109-117 (2015).</li><li>Monai, H., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Calcium+imaging+reveals+glial+involvement+in+transcranial+direct+current+stimulation-induced+plasticity+in+mouse+brain.">Calcium imaging reveals glial involvement in transcranial direct current stimulation-induced plasticity in mouse brain.</a> Nature Comm. 7, 11100 (2016).</li><li>Gellner, A. -. K., Reis, J., Fritsch, B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Glia:+A+Neglected+Player+in+Non-invasive+Direct+Current+Brain+Stimulation.">Glia: A Neglected Player in Non-invasive Direct Current Brain Stimulation.</a> Front Cell Neurosci. 10, 188 (2016).</li><li>Takano, Y., Yokawa, T., Masuda, A., Niimi, J., Tanaka, S., Hironaka, N. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+rat+model+for+measuring+the+effectiveness+of+transcranial+direct+current+stimulation+using+fMRI.">A rat model for measuring the effectiveness of transcranial direct current stimulation using fMRI.</a> Neurosci Lett. 491 (1), 40-43 (2011).</li><li>Islam, N., Moriwaki, A., Hattori, Y., Hori, Y. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Anodal+polarization+induces+protein+kinase+C+gamma+(PKC+gamma)-like+immunoreactivity+in+the+rat+cerebral+cortex.">Anodal polarization induces protein kinase C gamma (PKC gamma)-like immunoreactivity in the rat cerebral cortex.</a> Neurosci Res. 21, 169-172 (1994).</li><li>Islam, N., Aftabuddin, M., Moriwaki, A., Hattori, Y., Hori, Y. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Increase+in+the+calcium+level+following+anodal+polarization+in+the+rat+brain.">Increase in the calcium level following anodal polarization in the rat brain.</a> Brain Res. 684 (2), 206-208 (1995).</li><li>Rohan, J. G., Carhuatanta, K. A., McInturf, S. M., Miklasevich, M. K., Jankord, R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Modulating+Hippocampal+Plasticity+with+In+Vivo+Brain+Stimulation.">Modulating Hippocampal Plasticity with In Vivo Brain Stimulation.</a> J Neurosci. 35 (37), 12824-12832 (2015).</li><li>Wachter, D., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Transcranial+direct+current+stimulation+induces+polarity-specific+changes+of+cortical+blood+perfusion+in+the+rat.">Transcranial direct current stimulation induces polarity-specific changes of cortical blood perfusion in the rat.</a> Exp Neurol. 227 (2), 322-327 (2011).</li><li>Koo, H., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=After-effects+of+anodal+transcranial+direct+current+stimulation+on+the+excitability+of+the+motor+cortex+in+rats.">After-effects of anodal transcranial direct current stimulation on the excitability of the motor cortex in rats.</a> Rest Neurol Neurosci. 34 (5), 859-868 (2016).</li><li>Liebetanz, D., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=After-effects+of+transcranial+direct+current+stimulation+(tDCS)+on+cortical+spreading+depression.">After-effects of transcranial direct current stimulation (tDCS) on cortical spreading depression.</a> Neurosci Lett. 398 (1-2), 85-90 (2006).</li><li>Fregni, F., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Effects+of+transcranial+direct+current+stimulation+coupled+with+repetitive+electrical+stimulation+on+cortical+spreading+depression.">Effects of transcranial direct current stimulation coupled with repetitive electrical stimulation on cortical spreading depression.</a> Exp Neurol. 204 (1), 462-466 (2007).</li><li>Cambiaghi, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Flash+visual+evoked+potentials+in+mice+can+be+modulated+by+transcranial+direct+current+stimulation.">Flash visual evoked potentials in mice can be modulated by transcranial direct current stimulation.</a> Neurosci. 185, 161-165 (2011).</li><li>Dockery, C. A., Liebetanz, D., Birbaumer, N., Malinowska, M., Wesierska, M. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Cumulative+benefits+of+frontal+transcranial+direct+current+stimulation+on+visuospatial+working+memory+training+and+skill+learning+in+rats.">Cumulative benefits of frontal transcranial direct current stimulation on visuospatial working memory training and skill learning in rats.</a> Neurobiol Learn Mem. 96 (3), 452-460 (2011).</li><li>Faraji, J., Gomez-Palacio-Schjetnan, A., Luczak, A., Metz, G. 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A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Multi-session+transcranial+direct+current+stimulation+(tDCS)+elicits+inflammatory+and+regenerative+processes+in+the+rat+brain.">Multi-session transcranial direct current stimulation (tDCS) elicits inflammatory and regenerative processes in the rat brain.</a> PloS one. 7 (8), e43776 (2012).</li><li>Liebetanz, D., Koch, R., Mayenfels, S., K&#246;nig, F., Paulus, W., Nitsche, M. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Safety+limits+of+cathodal+transcranial+direct+current+stimulation+in+rats.">Safety limits of cathodal transcranial direct current stimulation in rats.</a> Clinical Neurophysiol. 120 (6), 1161-1167 (2009).</li><li>Yoon, K. J., Oh, B. -. M., Kim, D. -. Y. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Functional+improvement+and+neuroplastic+effects+of+anodal+transcranial+direct+current+stimulation+(tDCS)+delivered+1+day+vs.+1+week+after+cerebral+ischemia+in+rats.">Functional improvement and neuroplastic effects of anodal transcranial direct current stimulation (tDCS) delivered 1 day vs. 1 week after cerebral ischemia in rats.</a> Brain Res. 1452, 61-72 (2012).</li><li>Spezia Adachi, L. N., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Exogenously+induced+brain+activation+regulates+neuronal+activity+by+top-down+modulation:+conceptualized+model+for+electrical+brain+stimulation.">Exogenously induced brain activation regulates neuronal activity by top-down modulation: conceptualized model for electrical brain stimulation.</a> Exp Brain Res. 233 (5), 1377-1389 (2015).</li><li>Jackson, M. P., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Safety+parameter+considerations+of+anodal+transcranial+Direct+Current+Stimulation+in+rats.">Safety parameter considerations of anodal transcranial Direct Current Stimulation in rats.</a> Brain, behavior, and immunity. , (2017).</li><li>Ordek, G., Groth, J. D., Sahin, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Differential+effects+of+ketamine/xylazine+anesthesia+on+the+cerebral+and+cerebellar+cortical+activities+in+the+rat.">Differential effects of ketamine/xylazine anesthesia on the cerebral and cerebellar cortical activities in the rat.</a> J Neurophysiol. 109 (5), 1435-1443 (2013).</li><li>Sykes, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Differences+in+Motor+Evoked+Potentials+Induced+in+Rats+by+Transcranial+Magnetic+Stimulation+under+Two+Separate+Anesthetics:+Implications+for+Plasticity+Studies.">Differences in Motor Evoked Potentials Induced in Rats by Transcranial Magnetic Stimulation under Two Separate Anesthetics: Implications for Plasticity Studies.</a> Front Neural Circ. 10, 80 (2016).</li><li>Zhang, D. X., Levy, W. B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Ketamine+blocks+the+induction+of+LTP+at+the+lateral+entorhinal+cortex-dentate+gyrus+synapses.">Ketamine blocks the induction of LTP at the lateral entorhinal cortex-dentate gyrus synapses.</a> Brain Res. 593 (1), 124-127 (1992).</li></ol>

המחברים אין לחשוף.

פרוטוקול זה מתאר ושלבי למימוש כירורגי מלכודת מלון טס קבוע, כמו גם לגירוי עוקבות בחולדות התראה וחומרים טיפוסי. במהלך הכנת מכרסם מלון טס ניסוי, מספר היבטים מתודולוגיים (הבטיחות והסבילות של מלון טס, התוצאה פרמטר), כמו גם היבטים קונספטואליים (comparability עם מצב האדם, ההשפעה הצפויה של גירוי על מוח מס...

הממשל טראנס של זרמים חשמליים למוח (מלון טס) שימש במשך עשרות שנים ללמוד את תפקוד המוח, כדי לשנות את ההתנהגות. יותר לאחרונה, החלת ישיר, זרמים, או בתדירות נמוכה יותר זרמים חשמליים (טק ו- tRNS), noninvasively דרך הגולגולת ללא פגע על ידי שימוש אלקטרודות שניים או יותר (anode(s) ו- cathode(s)) צבר ריבית מדעית וקלינית. בפרט, tDCS שימש בהפעלות יותר 33,200 לנסיינים בריאים, חולים עם מחלות מנוטלי, התפתחה כמו כספת ופשוט, יישום המיטה חסכונית, עם הפוטנציאל הטיפולי אפשרי, כמו גם לטווח ארוך תופעות התנהגותיות1. זה בבירור הניב את הצורך המוגבר ואת עניין מדעי במחקרים מכניסטית, כולל היבטי בטיחות. מאמר זה מתמקד הצורה הנפוצה ביותר של גירוי, tDCS.
על פני מינים, tDCS ממיקרו דעתנית קורטיקליים ופלסטיות סינפטית. שינויים דעתנית דווחו תלויי-קוטביות שינוי של קצב ירי עצביים ספונטנית חולדות וחתולים2,3,4, או שינויים מנוע עורר פוטנציאליים (חבר הפרלמנט האירופי) amplitudes בין בני אדם (עכברים שניהם גדל ואחרי anodal ירד לאחר cathodal tDCS: האדם5,6; העכבר7). Anodal DCS גדלה היעילות סינפטית של מנוע בקליפת המוח או בהיפוקמפוס synapses במבחנה למשך מספר שעות לאחר גירוי או potentiation לטווח ארוך (LTP), כאשר שיתוף להחיל עם קלט מסוים סינפטית חלש או כאשר ניתנת לפני הפלסטיות וגורם לגירוי8,9,10,11,12. בהתאמה, היתרונות של גירוי על הצלחה אימונים מוטוריים או קוגניטיבי לעיתים קרובות מתגלים רק אם tDCS הוא שותף יישומית עם הדרכה8,13,14,15. בעוד ממצאים קודמים אלה מיוחסות בעיקר פונקציות של נוירונים, יצוין כי תאים שאינם עצבית (עכשיו, דונלד) עשוי לתרום גם תפקודית השפעות tDCS. למשל, רמות הסידן תאיים astrocytic גדל במהלך tDCS anodal עכברים התראה16. באופן דומה, tDCS anodal-צפיפות זרם מתחת לסף עבור הקשורים ניוון מוחיים המושרה הפעלה התלויים של מינון של מיקרוגלייה17. עם זאת, מודולציה של נוירון-עכשיו, דונלד אינטראקציה באמצעות tDCS צריך עוד חקירה ספציפיות.
מחקר ביחד, בעלי חיים צילום מתקדמות בבירור ההבנה שלנו של השפעת modulatory tDCS דעתנית, פלסטיות. עם זאת, יש נצפות "הפער translational הופכי" גידול מעריכי בפרסומי מחקרים tDCS אנושי בניגוד להאטה, קטין עלייה חקירות של המנגנון הבסיסי של מלון טס במבחנה , ויוו בבעלי חיים. בנוסף, מלון טס מכרסמים מודלים מבוצעים עם השתנות גבוהה מעבר מעבדות מחקר (החל transdermal גירוי epicranial), גירוי דווח על ההליכים הם לעתים קרובות אינם שקופים לגמרי. הפרעה comparability של ו replicability של מחקר בסיסי נתונים, כמו גם פרשנות של תוצאות.
כאן נתאר בפירוט מימוש מלכודת גירוי המוח טראנס מיקוד קליפת המוח המוטורית העיקרי, אשר מאפשר תרגום התנאי tDCS האנושי תוך מזעור השתנות, ומאפשר גירוי חוזרות ללא ניתוח הפרעה ההתנהגות. פרוטוקול צעד אחר צעד עבור מלון טס עוקבות בחולדות התראה מסופק. נדונים היבטים מתודולוגיים הרעיוני של היישום בטוח של מלון טס בחולדות התראה.

<table>
	<tbody>
		<tr>
			<td>Softasept N</td>
			<td>B. Braun Melsungen AG, 
			Melsungen, Deutschland</td>
			<td>3887138</td>
			<td>antiseptic agent</td>
		</tr>
		<tr>
			<td>Ethanol 70 %</td>
			<td>Carl Roth GmbH &#38; Co. KG, Karlsruhe, Deutschland</td>
			<td>T913.1</td>
			<td></td>
		</tr>
		<tr>
			<td>arched tip forceps</td>
			<td>FST Fine science tools, Heidelberg, Deutschland</td>
			<td>11071-10</td>
			<td></td>
		</tr>
		<tr>
			<td>Iris Forceps, 10cm, Straight, Serrated</td>
			<td>World Precision Instruments, Inc, Sarasota, FL, USA, Inc, Sarasota, FL, USA</td>
			<td>15914</td>
			<td></td>
		</tr>
		<tr>
			<td>Scalpel Handle #3, 13cm</td>
			<td>World Precision Instruments, Inc, Sarasota, FL, USA, Inc, Sarasota, FL, USA</td>
			<td>500236</td>
			<td></td>
		</tr>
		<tr>
			<td>Standard Scalpel Blade #10</td>
			<td>World Precision Instruments, Inc, Sarasota, FL, USA, Inc, Sarasota, FL, USA</td>
			<td>500239</td>
			<td></td>
		</tr>
		<tr>
			<td>Zelletten cellulose swabs</td>
			<td>Lohmann und Rauscher, Neuwied, Deutschland</td>
			<td>13349</td>
			<td>5 x 4 cm&#160;</td>
		</tr>
		<tr>
			<td>Isoflurane</td>
			<td>AbbVie Deutschland GmbH &#38; Co</td>
			<td>N01AB06</td>
			<td></td>
		</tr>
		<tr>
			<td>Iris Scissors, 11.5cm, Straight</td>
			<td>World Precision Instruments, Inc, Sarasota, FL, USA, Inc, Sarasota, FL, USA</td>
			<td>501758</td>
			<td>small scissors</td>
		</tr>
		<tr>
			<td>cotton swab/cotton buds</td>
			<td>Carl Roth GmbH &#38; Co. KG, Karlsruhe, Deutschland</td>
			<td>EH12.1</td>
			<td>Rotilabo</td>
		</tr>
		<tr>
			<td>Kelly Hemostatic Forceps, 14cm, Straight</td>
			<td>World Precision Instruments, Inc, Sarasota, FL, USA, Inc, Sarasota, FL, USA</td>
			<td>501241</td>
			<td>surgical clamp</td>
		</tr>
		<tr>
			<td>electrode plate (platinum)</td>
			<td>custom made</td>
			<td>Wissenschaftliche Werkstatt Neurozentrum Uniklinik Freiburg, Deutschland</td>
			<td>10x6 mm, 0.15 mm thickness</td>
		</tr>
		<tr>
			<td>insulated copper strands (~1 mm diameter)</td>
			<td>Reichelt elektronik GmbH &#38; Co. KG, Sande, Germany</td>
			<td>LITZE BL</td>
			<td>electrode cable</td>
		</tr>
		<tr>
			<td>Weller EC 2002 M soldering station</td>
			<td>Weller Tools GmbH, Besigheim, Germany</td>
			<td>EC2002M1D</td>
			<td></td>
		</tr>
		<tr>
			<td>Iso-Core EL 0,5 mm</td>
			<td>FELDER GMBH L&#246;ttechnik, Oberhausen, Deutschland</td>
			<td>20970510</td>
			<td>lead free solder</td>
		</tr>
		<tr>
			<td>MERSILENE Polyester Fiber Suture</td>
			<td>Johnson &#38; Johnson Medical GmbH, Ethicon Deutschland, Norderstedt, Germany</td>
			<td>R871H</td>
			<td>nonabsorbable braided suture, 4-0</td>
		</tr>
		<tr>
			<td>Histoacryl</td>
			<td>B. Braun Melsungen AG, 
			Melsungen, Deutschland</td>
			<td>9381104</td>
			<td>cyanoacrylate</td>
		</tr>
		<tr>
			<td>Ketamin 10%</td>
			<td>Medistar GmbH, Germany</td>
			<td>n/a</td>
			<td>anesthetics</td>
		</tr>
		<tr>
			<td>Rompun 2% (Xylazine)</td>
			<td>Bayer GmbH, Germany</td>
			<td>n/a</td>
			<td>anesthetics</td>
		</tr>
	</tbody>
</table>

transcranial electrical brain stimulation in alert rodents

גירוי חשמלי מוחי טראנס יכול לווסת דעתנית קורטיקליים ופלסטיות של בני אדם ומכרסמים. הצורה הנפוצה ביותר של גירוי אצל בני אדם הוא גירוי זרם ישיר טראנס (tDCS). בתדירות נמוכה יותר, טראנס זרם חילופין גירוי (טק) או טראנס רעש אקראי גירוי (tRNS), צורה מסוימת של טק באמצעות זרם חשמלי מוחל באופן אקראי בטווח תדר מוגדר מראש, משמש. העלייה חקר גירוי המוח החשמלי לא פולשנית בבני אדם, שניהם למטרות ניסויים קליניים, הניב צורך מוגבר בטיחות בסיסי, מכניסטית, מחקרים בבעלי חיים. מאמר זה מתאר מודל גירוי חשמלי מוחי טראנס (מלון טס) דרך הגולגולת שלם פילוח של המערכת המוטורית בחולדות התראה. הפרוטוקול מספק הוראות שלב אחר שלב הסידור כירורגי של שקע אלקטרודה epicranial קבועה בשילוב עם אלקטרודה מונה מושתל על החזה. על ידי הצבת של אלקטרודה לגירוי לתוך השקע epicranial, סוגי גירוי חשמלי שונים, להשוות tDCS טק, tRNS בבני אדם, יכולים להיגאל. יתר על כן, הם הציגו את צעדים מעשיים עבור מלון טס בחולדות התראה. צפיפות זרם יישומית, גירוי משך וסוג גירוי עשוי להיבחר בהתאם לצרכים ניסיוני. אזהרות, היתרונות והחסרונות של זה נידונות, כמו גם בטיחות וסבילות היבטים.

יישום שתואר מלכודת אמין מלון טס חוזרות בחולדות ההתראה ניתן לשלב בקלות מכניסטית ניסויים, מחקרים מנה-תגובה או ניסויים לרבות פעילויות התנהגותיות. עד כה, comparability של נתונים ממחקרים על בעלי חיים באמצעות מלון טס (לא פולשנית) מתעכבת על ידי ההשתנות של שבחבורה גירוי מלון טס בין מעב?...

Watch this Scientific Journal Video about Transcranial Electrical Brain Stimulation in Alert Rodents at JoVE.com

Transcranial Electrical Brain Stimulation in Alert Rodents

טראנס גירוי חשמלי מוחי בחולדות התראה

פרוטוקול זה מתאר מלכודת כירורגי שקע אלקטרודה epicranial קבוע, אלקטרודה חזה מושתל בחולדות. על ידי הצבת של האלקטרודה השנייה לתוך השקע, סוגים שונים של גירוי חשמלי מוחי טראנס יכולים להינתן על מערכת התנועה בבעלי התראה דרך הגולגולת ללא פגע.

Transcranial electrical brain stimulation can modulate cortical excitability and plasticity in humans and rodents. The most common form of stimulation in ...

transcranial-electrical-brain-stimulation-in-alert-rodents

Research

JoVE Journal

Neuroscience

10.6K Views.  Albert-Ludwigs-University Freiburg. פרוטוקול זה מתאר מלכודת כירורגי שקע אלקטרודה epicranial קבוע, אלקטרודה חזה מושתל בחולדות. על ידי הצבת של האלקטרודה השנייה לתוך השקע, סוגים שונים של גירוי חשמלי מוחי טראנס יכולים להינתן על מערכת התנועה בבעלי התראה דרך הגולגולת ללא פגע.

Video: Transcranial Electrical Brain Stimulation in Alert Rodents

Combining Transcranial Magnetic Stimulation and fMRI to Examine the Default Mode Network

The default mode network is a group of brain regions that are active when an individual is not focused on the outside world and the brain is at "wakeful rest."1,2,3 It is thought the default mode network corresponds to self-referential or "internal mentation".2,3
It has been hypothesized that, in humans, activity within the default mode network is correlated with certain pathologies (for instance, hyper-activation has been linked to schizophrenia 4,5,6 and autism spectrum disorders 7 whilst hypo-activation of the network has been linked to Alzheimer's and other neurodegenerative diseases 8). As such, noninvasive modulation of this network may represent a potential therapeutic intervention for a number of neurological and psychiatric pathologies linked to abnormal network activation. One possible tool to effect this modulation is Transcranial Magnetic Stimulation: a non-invasive neurostimulatory and neuromodulatory technique that can transiently or lastingly modulate cortical excitability (either increasing or decreasing it) via the application of localized magnetic field pulses.9
In order to explore the default mode network's propensity towards and tolerance of modulation, we will be combining TMS (to the left inferior parietal lobe) with functional magnetic resonance imaging (fMRI). Through this article, we will examine the protocol and considerations necessary to successfully combine these two neuroscientific tools.

In this article, we examine the methodology and considerations relevant to the combination of TMS and fMRI to examine the effects of brain stimulation on the default network.

שילוב של גירוי מגנטי fMRI Transcranial ולבחון את רשת מצב ברירת מחדל

The default mode network is a group of brain regions that are active when an individual is not focused on the outside world and the brain is at "wakeful ...

TMS: Using the Theta-Burst Protocol to Explore Mechanism of Plasticity in Individuals with Fragile X Syndrome and Autism

Fragile X Syndrome (FXS), also known as Martin-Bell Syndrome, is a genetic abnormality found on the X chromosome.1,2 Individuals suffering from FXS display abnormalities in the expression of FMR1 - a protein required for typical, healthy neural development.3 Recent data has suggested that the loss of this protein can cause the cortex to be hyperexcitable thereby affecting overall patterns of neural plasticity.4,5
In addition, Fragile X shows a strong comorbidity with autism: in fact, 30% of children with FXS are diagnosed with autism, and 2 - 5% of autistic children suffer from FXS.6
Transcranial Magnetic Stimulation (a non-invasive neurostimulatory and neuromodulatory technique that can transiently or lastingly modulate cortical excitability via the application of localized magnetic field pulses 7,8) represents a unique method of exploring plasticity and the manifestations of FXS within affected individuals. More specifically, Theta-Burst Stimulation (TBS), a specific stimulatory protocol shown to modulate cortical plasticity for a duration up to 30 minutes after stimulation cessation in healthy populations, has already proven an efficacious tool in the exploration of abnormal plasticity.9,10 
Recent studies have shown the effects of TBS last considerably longer in individuals on the autistic spectrum - up to 90 minutes.11 This extended effect-duration suggests an underlying abnormality in the brain's natural plasticity state in autistic individuals - similar to the hyperexcitability induced by Fragile X Syndrome.
In this experiment, utilizing single-pulse motor-evoked potentials (MEPs) as our benchmark, we will explore the effects of both intermittent and continuous TBS on cortical plasticity in individuals suffering from FXS and individuals on the Autistic Spectrum.

In this article, we examine the effects of Theta-Burst TMS stimulation on cortical plasticity in individuals suffering from Fragile X syndrome and individuals on the autistic spectrum.

TMS: שימוש בפרוטוקול תטא-Burst לחקור Mechasnism של פלסטיות של אנשים עם תסמונת X שביר אוטיזם ו

Fragile X Syndrome (FXS), also known as Martin-Bell Syndrome, is a genetic abnormality found on the X chromosome.1,2 Individuals suffering from FXS ...

The NeuroStar TMS Device: Conducting the FDA Approved Protocol for Treatment of Depression

The Neuronetics NeuroStar Transcranial Magnetic Stimulation (TMS) System is a class II medical device that produces brief duration, pulsed magnetic fields. These rapidly alternating fields induce electrical currents within localized, targeted regions of the cortex which are associated with various physiological and functional brain changes.1,2,3
In 2007, O'Reardon et al., utilizing the NeuroStar device, published the results of an industry-sponsored, multisite, randomized, sham-stimulation controlled clinical trial in which 301 patients with major depression, who had previously failed to respond to at least one adequate antidepressant treatment trial, underwent either active or sham TMS over the left dorsolateral prefrontal cortex (DLPFC). The patients, who were medication-free at the time of the study, received TMS five times per week over 4-6 weeks.4
The results demonstrated that a sub-population of patients (those who were relatively less resistant to medication, having failed not more than two good pharmacologic trials) showed a statistically significant improvement on the Montgomery-Asberg Depression Scale (MADRS), the Hamilton Depression Rating Scale (HAMD), and various other outcome measures. In October 2008, supported by these and other similar results5,6,7, Neuronetics obtained the first and only Food and Drug Administration (FDA) approval for the clinical treatment of a specific form of medication-refractory depression using a TMS Therapy device (FDA approval K061053).
In this paper, we will explore the specified FDA approved NeuroStar depression treatment protocol (to be administered only under prescription and by a licensed medical profession in either an in- or outpatient setting).

In this article, we examine the methodology and considerations relevant to the FDA approved depression treatment protocol using the Neuronetics NeuroStar TMS device.

התקן TMS NeuroStar: ניהול ה-FDA פרוטוקול מאושר לטיפול דיכאון

The Neuronetics NeuroStar Transcranial Magnetic Stimulation (TMS) System is a class II medical device that produces brief duration, pulsed magnetic ...

Electrode Positioning and Montage in Transcranial Direct Current Stimulation

Transcranial direct current stimulation (tDCS) is a technique that has been intensively investigated in the past decade as this method offers a non-invasive and safe alternative to change cortical excitability2. The effects of one session of tDCS can last for several minutes, and its effects depend on polarity of stimulation, such as that cathodal stimulation induces a decrease in cortical excitability, and anodal stimulation induces an increase in cortical excitability that may last beyond the duration of stimulation6. These effects have been explored in cognitive neuroscience and also clinically in a variety of neuropsychiatric disorders &#x2013; especially when applied over several consecutive sessions4. One area that has been attracting attention of neuroscientists and clinicians is the use of tDCS for modulation of pain-related neural networks3,5. Modulation of two main cortical areas in pain research has been explored: primary motor cortex and dorsolateral prefrontal cortex7. Due to the critical role of electrode montage, in this article, we show different alternatives for electrode placement for tDCS clinical trials on pain; discussing advantages and disadvantages of each method of stimulation.

Transcranial direct current stimulation (tDCS) is an established technique to modulate cortical excitability1,2. It has been used as an investigative tool in neuroscience due to its effects on cortical plasticity, easy operation, and safe profile. One area that tDCS has been showing encouraging results is pain alleviation 3-5.

אלקטרודה מיצוב ו מונטאז גירוי ישיר Transcranial נוכחי

Transcranial direct current stimulation (tDCS) is a technique that has been intensively investigated in the past decade as this method offers a ...

Deep Brain Stimulation with Simultaneous fMRI in Rodents

In order to visualize the global and downstream neuronal responses to deep brain stimulation (DBS) at various targets, we have developed a protocol for using blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) to image rodents with simultaneous DBS. DBS fMRI presents a number of technical challenges, including accuracy of electrode implantation, MR artifacts created by the electrode, choice of anesthesia and paralytic to minimize any neuronal effects while simultaneously eliminating animal motion, and maintenance of physiological parameters, deviation from which can confound the BOLD signal.&#160;Our laboratory has developed a set of procedures that are capable of overcoming most of these possible issues. For electrical stimulation, a homemade tungsten bipolar microelectrode is used, inserted stereotactically at the stimulation site in the anesthetized subject. In preparation for imaging, rodents are fixed on a plastic headpiece and transferred to the magnet bore. For sedation and paralysis during scanning, a cocktail of dexmedetomidine and pancuronium is continuously infused, along with a minimal dose of isoflurane; this preparation minimizes the BOLD ceiling effect of volatile anesthetics. In this example experiment, stimulation of the subthalamic nucleus (STN) produces BOLD responses which are observed primarily in ipsilateral cortical regions, centered in motor cortex. Simultaneous DBS and fMRI allows the unambiguous modulation of neural circuits dependent on stimulation location and stimulation parameters, and permits observation of neuronal modulations free of regional bias. This technique may be used to explore the downstream effects of modulating neural circuitry at nearly any brain region, with implications for both experimental and clinical DBS.

This protocol describes a standard method for simultaneous functional magnetic resonance imaging and deep brain stimulation in the rodent. The combined use of these experimental tools allows for the exploration of global downstream activity in response to electrical stimulation at virtually any brain target.

גירוי מוחי עמוק עם fMRI סימולטני במכרסמים

In order to visualize the global and downstream neuronal responses to deep brain stimulation (DBS) at various targets, we have developed a protocol for ...

Acrylic Resin Molding Based Head Fixation Technique in Rodents

Head fixation is a technique of immobilizing animal's head by attaching a head-post on the skull for rigid clamping. Traditional head fixation requires surgical attachment of metallic frames on the skull. The attached frames are then clamped to a stationary platform resulting in immobilization of the head. However, metallic frames for head fixation have been technically difficult to design and implement in general laboratory environment. In this study, we provide a novel head fixation method. Using a custom-made head fixation bar, head mounter is constructed during implantation surgery. After the application of acrylic resin for affixing implants such as electrodes and cannula on the skull, additional resins applied on top of that to build a mold matching to the port of the fixation bar. The molded head mounter serves as a guide rails, investigators conveniently fixate the animal&#8217;s head by inserting the head mounter into the port of the fixation bar. This method could be easily applicable if implantation surgery using dental acrylics is necessary and might be useful for laboratories that cannot easily fabricate CNC machined metal head-posts.

Traditional head fixation techniques have used metallic frames attached on the skull as an interface for head fixation apparatus. This protocol demonstrates a frameless, acrylic resin molding based head fixation technique for behavioral tasks in rodents.

טכניקת קיבוע אקריליק שרף דפוס מבוסס ראש במכרסמים

Head fixation is a technique of immobilizing animal's head by attaching a head-post on the skull for rigid clamping. Traditional head fixation requires ...

Effects of Transcranial Alternating Current Stimulation on the Primary Motor Cortex by Online Combined Approach with Transcranial Magnetic Stimulation

Transcranial Alternating Current Stimulation (tACS) is a neuromodulatory technique able to act through sinusoidal electrical waveforms in a specific frequency and in turn modulate ongoing cortical oscillatory activity. This neurotool allows the establishment of a causal link between endogenous oscillatory activity and behavior. Most of the tACS studies have shown online effects of tACS. However, little is known about the underlying action mechanisms of this technique because of the AC-induced artifacts on Electroencephalography (EEG) signals. Here we show a unique approach to investigate online physiological frequency-specific effects of tACS of the primary motor cortex (M1) by using single pulse Transcranial Magnetic Stimulation (TMS) to probe cortical excitability changes. In our setup, the TMS coil is placed over the tACS electrode while Motor Evoked Potentials (MEPs) are collected to test the effects of the ongoing M1-tACS. So far, this approach has mainly been used to study the visual and motor systems. However, the current tACS-TMS setup can pave the way for future investigations of cognitive functions. Therefore, we provide a step-by-step manual and video guidelines for the procedure.

Transcranial Alternating Current Stimulation (tACS) allows the modulation of cortical excitability in a frequency-specific fashion. Here we show a unique approach which combines online tACS with single pulse Transcranial Magnetic Stimulation (TMS) in order to "probe" cortical excitability by means of Motor Evoked Potentials.

ההשפעות של גירוי זרם חילופין טראנס על קליפת המוח המוטורית הראשי על-ידי גישה משולבת מקוון עם גירוי מגנטי טראנס

Transcranial Alternating Current Stimulation (tACS) is a neuromodulatory technique able to act through sinusoidal electrical waveforms in a specific ...

Chronic Transcranial Electrical Stimulation and Intracortical Recording in Rats

Transcranial electrical stimulation (TES) is a powerful and relatively simple approach to diffusely influence brain activity either randomly or in a closed-loop event-triggered manner. Although many studies are focusing on the possible benefits and side-effects of TES in healthy and pathologic brains, there are still many fundamental open questions regarding the mechanism of action of the stimulation. Therefore, there is a clear need for a robust and reproducible method to test the acute and the chronic effects of TES in rodents. TES can be combined with regular behavioral, electrophysiological, and imaging techniques to investigate neuronal networks in vivo. The implantation of transcranial stimulation electrodes does not impose extra constraints on the experimental design while it offers a versatile, flexible tool to manipulate brain activity. Here we provide a detailed, step-by-step protocol to fabricate and implant transcranial stimulation electrodes to influence brain activity in a temporally constrained manner for months.

This detailed protocol describes transcranial stimulation electrode placement on the temporal bone in order to investigate the short- and long-term effects of transcranial electrical stimulation in freely moving rats.

גירוי חשמלי טראנס כרונית והקלטה Intracortical בחולדות

Transcranial electrical stimulation (TES) is a powerful and relatively simple approach to diffusely influence brain activity either randomly or in a ...

Combined Transcranial Magnetic Stimulation and Electroencephalography of the Dorsolateral Prefrontal Cortex

Transcranial magnetic stimulation (TMS) is a non-invasive method that produces neural excitation in the cortex by means of brief, time-varying magnetic field pulses. The initiation of cortical activation or its modulation depends on the background activation of the neurons of the cortical region activated, the characteristics of the coil, its position and its orientation with respect to the head. TMS combined with simultaneous electrocephalography (EEG) and neuronavigation (nTMS-EEG) allows for the assessment of cortico-cortical excitability and connectivity in almost all cortical areas in a reproducible manner. This advance makes nTMS-EEG a powerful tool that can accurately assess brain dynamics and neurophysiology in test-retest paradigms that are required for clinical trials. Limitations of this method include artifacts that cover the initial brain reactivity to stimulation. Thus, the process of removing artifacts may also extract valuable information. Moreover, the optimal parameters for dorsolateral prefrontal (DLPFC) stimulation are not fully known and current protocols utilize variations from the motor cortex (M1) stimulation paradigms. However, evolving nTMS-EEG designs hope to address these issues. The protocol presented here introduces some standard practices for assessing neurophysiological functioning from stimulation to the DLPFC that can be applied in patients with treatment resistant psychiatric disorders that receive treatment such as transcranial direct current stimulation (tDCS), repetitive transcranial magnetic stimulation (rTMS), magnetic seizure therapy (MST) or electroconvulsive therapy (ECT).

The protocol presented here is for TMS-EEG studies utilizing intracortical excitability test-retest design paradigms. The intent of the protocol is to produce reliable and reproducible cortical excitability measures for assessing neurophysiological functioning related to therapeutic interventions in the treatment of neuropsychiatric diseases such as major depression.

גירוי מגנטי טראנס המשולבת ואת אלקטרואנצפלוגרם של קליפת המוח הקדם חזיתית דורסולטרלי

Transcranial magnetic stimulation (TMS) is a non-invasive method that produces neural excitation in the cortex by means of brief, time-varying magnetic ...

Transcranial Direct Current Stimulation (tDCS) in Mice

Transcranial direct current stimulation (tDCS) is a non-invasive neuromodulation technique proposed as an alternative or complementary treatment for several neuropsychiatric diseases. The biological effects of tDCS are not fully understood, which is in part explained due to the difficulty in obtaining human brain tissue. This protocol describes a tDCS mouse model that uses a chronically implanted electrode allowing the study of the long-lasting biological effects of tDCS. In this experimental model, tDCS changes the cortical gene expression and offers a prominent contribution to the understanding of the rationale for its therapeutic use.

Transcranial Direct Current Stimulation tDCS in Mice

Transcranial direct current stimulation (tDCS) is a therapeutic technique proposed to treat psychiatric diseases. An animal model is essential for understanding the specific biological alterations evoked by tDCS. This protocol describes a tDCS mouse model that uses a chronically implanted electrode.

טראנס זרם ישיר גירוי (tDCS) בעכברים

Transcranial direct current stimulation (tDCS) is a non-invasive neuromodulation technique proposed as an alternative or complementary treatment for ...