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. 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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. 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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. -. 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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,&lt;br/&gt; Melsungen, Deutschland</td><td>3887138</td><td>antiseptic agent</td></tr><tr><td>Ethanol 70 %</td><td>Carl Roth GmbH &amp;amp; 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&amp;nbsp;</td></tr><tr><td>Isoflurane</td><td>AbbVie Deutschland GmbH &amp;amp; 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 &amp;amp; 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 &amp;amp; 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&amp;ouml;ttechnik, Oberhausen, Deutschland</td><td>20970510</td><td>lead free solder</td></tr><tr><td>MERSILENE Polyester Fiber Suture</td><td>Johnson &amp;amp; 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,&lt;br/&gt; 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

Repetitive Transcranial Magnetic Stimulation to the Unilateral Hemisphere of Rat Brain

Previous rodent models of repetitive transcranial magnetic stimulation (rTMS) adopted whole-brain stimulation instead of unilateral hemispheric rTMS, which is unlike the protocols used for human subjects. We report a successful application of rTMS to the unilateral hemisphere of rat brain. The rTMS was delivered with a low-frequency (1 Hz), high-frequency (20 Hz), or sham stimulation protocol to one side of the brain by using a small 25-mm figure-8 coil. We placed the center of the coil 1 cm lateral to the vertex on the biauricular line and angulated the coil 45&#176; to the ground to minimize a potential direct effect of rTMS on the contralateral cortex. We also used an in-house water cooling system to enable repetitive magnetic stimulation for more than 20 min, even at a 20-Hz stimulation frequency. Increases in the transcriptions of immediate early genes (Arc, Junb, and Egr2) were greater after rTMS than after sham stimulation. After 5 consecutive days of 20-min 1-Hz rTMS, bdnf mRNA expression was significantly higher in stimulated cortex than in contralateral side. The model presented herein will elucidate the molecular mechanisms of rTMS by allowing analysis of the inter-hemispheric difference in its effect.

We applied repetitive transcranial magnetic stimulation (rTMS) to the unilateral hemisphere of rat brain, by placing a 25-mm figure-8 coil 1 cm lateral to the vertex on the biauricular line and angulating the coil by 45&#176;. An in-house water cooling system was used for rTMS for more than 20 min.

גירוי מגנטי Transcranial חוזרים אל חצי הכדור החד-צדדית של המוח עכברוש

Previous rodent models of repetitive transcranial magnetic stimulation (rTMS) adopted whole-brain stimulation instead of unilateral hemispheric rTMS, ...

Behavior

A Wireless, Bidirectional Interface for In Vivo Recording and Stimulation of Neural Activity in Freely Behaving Rats

In vivo electrophysiology is a powerful technique to investigate the relationship between brain activity and behavior at a millisecond and micrometer scale. However, current methods mostly rely on tethered cable recordings or only use unidirectional systems, allowing either recording or stimulation of neural activity, but not at the same time or same target. Here, a new wireless, bidirectional device for simultaneous multichannel recording and stimulation of neural activity in freely behaving rats is described. The system operates through a single portable head stage that both transmits recorded activity and can be targeted in real-time for brain stimulation using a telemetry-based multichannel software. The head stage is equipped with a preamplifier and a rechargeable battery, allowing stable long-term recordings or stimulation for up to 1 h. Importantly, the head stage is compact, weighs 12 g (including battery) and thus has minimal impact on the animal&#180;s behavioral repertoire, making the method applicable to a broad set of behavioral tasks. Moreover, the method has the major advantage that the effect of brain stimulation on neural activity and behavior can be measured simultaneously, providing a tool to assess the causal relationships between specific brain activation patterns and behavior. This feature makes the method particularly valuable for the field of deep brain stimulation, allowing precise assessment, monitoring, and adjustment of stimulation parameters during long-term behavioral experiments. The applicability of the system has been validated using the inferior colliculus as a model structure.

A Wireless, Bidirectional Interface for In Vivo Recording and Stimulation of Neural Activity in Freely Behaving Rats

A wireless, bidirectional system for multi-channel neural recordings and stimulation in freely behaving rats is introduced. The system is light and compact, thus having minimal impact on the animal&#180;s behavioral repertoire. Moreover, this bidirectional system provides a sophisticated tool to assess causal relationships between brain activation patterns and behavior.

חיבור אלחוטי, ממשק דו-כיווני ההקלטה In Vivo גירוי של פעילות עצבית להתנהג בחופשיות חולדות

In vivo electrophysiology is a powerful technique to investigate the relationship between brain activity and behavior at a millisecond and micrometer ...

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 ...

Microelectrode Guided Implantation of Electrodes into the Subthalamic Nucleus of Rats for Long-term Deep Brain Stimulation

Deep brain stimulation (DBS) is a widely used and effective therapy for several neurologic disorders, such as idiopathic Parkinson&#8217;s disease, dystonia or tremor. DBS is based on the delivery of electrical stimuli to specific deep anatomic structures of the central nervous system. However, the mechanisms underlying the effect of DBS remain enigmatic. This has led to an interest in investigating the impact of DBS in animal models, especially in rats. As DBS is a long-term therapy, research should be focused on molecular-genetic changes of neural circuits that occur several weeks after DBS. Long-term DBS in rats is challenging because the rats move around in their cage, which causes problems in keeping in place the wire leading from the head of the animal to the stimulator. Furthermore, target structures for stimulation in the rat brain are small and therefore electrodes cannot easily be placed at the required position. Thus, a set-up for long-lasting stimulation of rats using platinum/iridium electrodes with an impedance of about 1 M&#937; was developed for this study. An electrode with these specifications allows for not only adequate stimulation but also recording of deep brain structures to identify the target area for DBS. In our set-up, an electrode with a plug for the wire was embedded in dental cement with four anchoring screws secured onto the skull. The wire from the plug to the stimulator was protected by a stainless-steel spring. A swivel was connected to the circuit to prevent the wire from becoming tangled. Overall, this stimulation set-up offers a high degree of free mobility for the rat and enables the head plug, as well as the wire connection between the plug and the stimulator, to retain long-lasting strength.

A method for implanting electrodes into the subthalamic nucleus (STN) of rats is described. Better localization of the STN was achieved by using a microrecording system. Furthermore, a stimulation set-up is presented that is characterized by long-lasting connections between the head of the animal and the stimulator.

Microelectrode מודרך השרשה של אלקטרודות לתוך גרעין Subthalamic של חולדות לטווח ארוך עמוק גירוי המוח

Deep brain stimulation (DBS) is a widely used and effective therapy for several neurologic disorders, such as idiopathic Parkinson&#8217;s disease, ...

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 ...

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 ...

Establishment of Acute Pontine Infarction in Rats by Electrical Stimulation

Pontine infarction is the most common stroke subtype in the posterior circulation, while there lacks a rodent model mimicking pontine infarction. Provided here is a protocol for successfully establishing a rat model of acute pontine infarction. Rats weighing about 250 g are used, and a probe with an insulated sheath is injected into the pons using a stereotaxic apparatus. A lesion is produced by the electrical stimulation with a single pulse. The Longa score, Berderson score, and beam balance test are used to assess neurological deficits. Additionally, the adhesive-removal somatosensory test is used to determine sensorimotor function, and the limb placement test is used to evaluate proprioception. MRI scans are then used to assess the infarction in vivo, and TTC staining is used to confirm the infarction in vitro. Here, a successful infarction is identified that is located in the anterolateral basis of the rostral pons. In conclusion, a new method is described to establish an acute pontine infarction rat model.

Presented here is a protocol for establishing acute pontine infarction in a rat model via electrical stimulation with a single pulse.

הקמת אוטם פונטינה חריפה בחולדות על ידי גירוי חשמלי

Pontine infarction is the most common stroke subtype in the posterior circulation, while there lacks a rodent model mimicking pontine infarction. Provided ...

Head Implants for the Neuroimaging of Awake, Head-Fixed Rats

Anesthetics, commonly used in preclinical and fundamental scientific research, have a depressive influence on the metabolic, neuronal, and vascular functions of the brain and can adversely influence neurophysiological results. The use of awake animals for research studies is advantageous but poses the major challenge of keeping the animals calm and stationary to minimize motion artifacts throughout data acquisition. Awake imaging in smaller-sized rodents (e.g., mice) is very common but remains scant in rats as rats are bigger, stronger, and have a greater tendency to oppose movement restraints and head fixation over the long durations required for imaging. A new model of neuroimaging of awake, head-fixed rats using customized hand-sewn slings, 3D-printed head implants, head caps, and a headframe is described. The results acquired following a single trial of single-whisker stimulation suggest an increase in the intensity of the evoked functional response. The acquisition of the evoked functional response from awake, head-fixed rats is faster than that from anesthetized rats, reliable, reproducible, and can be used for repeated longitudinal studies.

A detailed new procedure for functional imaging of awake, head-fixed rats is described.

שתלי ראש לדימות מוחי של חולדות ערות ומקובעות ראש

Anesthetics, commonly used in preclinical and fundamental scientific research, have a depressive influence on the metabolic, neuronal, and vascular ...

גירוי מוח עכבר עם EEG בעלות נמוכה וסליל בגודל מילימטרי

Low-Cost Electroencephalographic Recording System Combined with a Millimeter-Sized Coil to Transcranially Stimulate the Mouse Brain In Vivo

A low-cost electroencephalographic (EEG) recording system is proposed here to drive transcranial magnetic stimulation (TMS) of the mouse brain in vivo, utilizing a millimeter-sized coil. Using conventional screw electrodes combined with a custom-made, flexible, multielectrode array substrate, multi-site recording can be carried out from the mouse brain. In addition, we explain how a millimeter-sized coil is produced using low-cost equipment usually found in laboratories. Practical procedures for fabricating the flexible multielectrode array substrate and the surgical implantation technique for screw electrodes are also presented, which are necessary to produce low-noise EEG signals. Although the methodology is useful for recording from the brain of any small animal, the present report focuses on electrode implementation in an anesthetized mouse skull. Furthermore, this method can be easily extended to an awake small animal that is connected with tethered cables via a common adapter and fixed with a TMS device to the head during recording.The present version of the EEG-TMS system, which can include a maximum of 32 EEG channels (a device with 16 channels is presented as an example with fewer channels) and one TMS channel device, is described. Additionally, typical results obtained by the application of the EEG-TMS system to anesthetized mice are briefly reported.

Author Spotlight: מערכת הקלטה אלקטרואנצפלוגרפית בעלות נמוכה בשילוב עם סליל בגודל מילימטר כדי לגרות באופן טרנס-גולגולתי את מוח העכבר in vivo  

A low-cost electroencephalographic recording system combined with a millimeter-sized coil is proposed to drive transcranial magnetic stimulation of the mouse brain in vivo. Using conventional screw electrodes with a custom-made, flexible, multielectrode array substrate, multi-site recording can be carried out from the mouse brain in response to transcranial magnetic stimulation.

מערכת הקלטה אלקטרואנצפלוגרפית בעלות נמוכה בשילוב עם סליל בגודל מילימטר כדי לגרות באופן טרנס-גולגולתי את מוח העכבר in vivo

A low-cost electroencephalographic (EEG) recording system is proposed here to drive transcranial magnetic stimulation (TMS) of the mouse brain in vivo, ...

מיפוי זרימת דם מוחית ושדות חשמליים: מיקום אלקטרודות בעכברים

Placement of Extracranial Stimulating Electrodes and Measurement of Cerebral Blood Flow and Intracranial Electrical Fields in Anesthetized Mice

The detection of cerebral blood flow (CBF) responses to various forms of neuronal activation is critical for understanding dynamic brain function and variations in the substrate supply to the brain. This paper describes a protocol for measuring CBF responses to transcranial alternating current stimulation (tACS). Dose-response curves are estimated both from the CBF change occurring with tACS (mA) and from the intracranial electric field (mV/mm). We estimate the intracranial electrical field based on the different amplitudes measured by glass microelectrodes within each side of the brain. In this paper, we describe the experimental setup, which involves using either bilateral laser Doppler (LD) probes or laser speckle imaging (LSI) to measure the CBF; as a result, this setup requires anesthesia for the electrode placement and stability. We present a correlation between the CBF response and the current as a function of age, showing a significantly larger response at higher currents (1.5 mA and 2.0 mA) in young control animals (12-14 weeks) compared to older animals (28-32 weeks) (p &lt; 0.005 difference). We also demonstrate a significant CBF response at electrical field strengths &lt;5 mV/mm, which is an important consideration for eventual human studies. These CBF responses are also strongly influenced by the use of anesthesia compared to awake animals, the respiration control (i.e., intubated vs. spontaneous breathing), systemic factors (i.e., CO2), and local conduction within the blood vessels, which is mediated by pericytes and endothelial cells. Likewise, more detailed imaging/recording techniques may limit the field size from the entire brain to only a small region. We describe the use of extracranial electrodes for applying tACS stimulation, including both homemade and commercial electrode designs for rodents, the concurrent measurement of the CBF and intracranial electrical field using bilateral glass DC recording electrodes, and the imaging approaches. We are currently applying these techniques to implement a closed-loop format for augmenting the CBF in animal models of Alzheimer's disease and stroke.

מחבר זרקור: גישה מבוססת גירוי לשיפור זרימת הדם במוח במודל של אלצהיימר 

We describe a protocol for assessing dose-response curves for extracranial stimulation in terms of brain electrical field measurements and a relevant biomarker-cerebral blood flow. Since this protocol involves invasive electrode placement into the brain, general anesthesia is needed, with spontaneous breathing preferred rather than controlled respirations.

מיקום אלקטרודות מעוררות חוץ-גולגולתיות ומדידת זרימת דם מוחית ושדות חשמליים תוך גולגולתיים בעכברים מורדמים

The detection of cerebral blood flow (CBF) responses to various forms of neuronal activation is critical for understanding dynamic brain function and ...