MSB is supported by the Alcohol Beverage Medical Research Foundation, a Center for Translational Research Award (UL1 TR000058), the National Institutes for Alcohol Abuse and Alcoholism (P50 AA022537), and startup funds provided by the Virginia Higher Education Equipment Trust Fund and the VCU School of Medicine.

<ol>
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None of the authors have competing or conflicting interests.

الإجراء المقدمة هنا هو وسيلة فعالة لتصنيع حقنة عادية microinjection وmicroinjectors التي من شأنها أن تساعد في توضيح ركائز الجزيئية للسلوك دوافع. يوفر هذا الأسلوب عدة مزايا. أولا، من خلال تصنيع يزرع وmicroinjectors الخاصة واحد، والمعلمات التجريبية رواية يمكن أن يكون الأمثل بسرعة، أي واحدة لا تحتاج إلى الانتظار لمكونات العرف للوصول. ثانيا، نظرا لقطرها صغير من قنية، والمزيد من حقنة عادية يمكن زرعها في وقت واحد. هذا تقصير الوقت الجراحية المطلوبة، التي يمكن أن تحسن البقاء على قيد الحياة، ويسمح أيضا يزرع متعددة لكل حيوان. ثالثا، البرمجيات المستخدمة للتحكم في غرف استثابي يستوعب بسهولة جداول نسبة التقدمية منذ نسبة نموذج ثابت يمكن تحويلها بسرعة إلى نسبة التدريجي نموذج ببساطة عن طريق تطبيق قائمة المعلمة انتقال الحدث الذي يحتوي على جدول التعزيز المطلوب. أن تكونمفيدة على نطاق واسع، وعرضت إجراء microinjection العامة التي يجب أن تكون قابلة للتطبيق على نطاق واسع لMicroinjection من ما يقرب من أي كاشف المتاحة حاليا. وبالتالي، فإننا نتوقع أن هذه التقنية سوف تستمر في أن تكون ذات فائدة عالية مماثلة في المستقبل مع تعديلات طفيفة. عن طريق تغيير سوى عدد قليل من المتغيرات، وهذا النهج يمكن تطبيقها على عدد كبير من المواد الكيميائية. المعلمات التي من شأنها أن الأكثر شيوعا معالجته تشمل طول أن يبرز على microinjector من قنية، وحجم الحقن، ومعدل الحقن. على سبيل المثال، يمكن للمرء تريد حاقن لزيادة تبرز من طرف قنية لتجنب ندبة الدبقية التي تشكل عادة حوالي يزرع المزمنة. بالإضافة إلى ذلك، قد ترغب احدة لحقن حجم أكبر. لإبر دقيقة جدا الفيروس الجسم المخطط، وعادة ما تستخدم لحجم 1 ميكرولتر ويتم حقن هذا الحجم عادة على مدى فترة أطول من الزمن (في كثير من الأحيان 7-10 دقيقة بالإضافة إلى 3-10 دقيقة إضافية الوقت نشرها) مقارنة بما كان عليه استخدامد للمواد الدوائية (عادة 0،3-0،5 ميكرولتر أكثر من 2-3 دقيقة زائد 1-3 دقيقة وقت الانتشار إضافية). يجب على المستخدم أن تتشاور مع الأدب و / أو تجريبيا تحديد المعايير الأنسب لاحتياجاتهم. بغض النظر، فإن نجاح هذا الإجراء يعتمد بشكل حاسم على 4 المتغيرات: 1) طول قنية، 2) طول microinjector، 3) نوعية نمط الرش microinjector، و4) سلامة النظام قبل الحقن. لأن موقع microinjection يعتمد على عمق يبرز في microinjector من قنية، لا بد من أن كلا من حقنة عادية (الخطوة 1.2.8) وطول microinjector (آخر الانحناء، الخطوة 2.2.1) وكلاهما يعرف على وجه التحديد وموحدة بين جميع المواد الدراسية . هذا يمكن بسهولة أن يسيطر عليها بسهولة رفض أي تنفيذ هذا ليس هو طول المطلوب في النهائي إعادة القياس. وعلاوة على ذلك، لا يمكن توقع موقع الحقن في حال حدوثه على الفور تحت قنية دليل. وبالتالي، فإن أي microinjector أن ظبيةق تقم برش طويل، تيار غرامة على اختبار (خطوات 2.4.6) يجب رفضه. ويرتبط حقن الجودة أيضا لسلامة النظام قبل الحقن. إذا بعد الاستغناء عن المياه من حاقن (قبل ملء مع كاشف) لوحظت بقع متعددة على مسح المختبر، ثم يحتاج إلى تسرب لمعالجتها (ملاحظة على الخطوة 2.4.8). وعلاوة على ذلك، إذا كان فقاعة (الخطوة 2.4.9) الذي يفصل الدواء من الماء في أنابيب PE20 ليست واحدة، فقاعة واحدة (بعد ملء microinjector مع كاشف)، ومن ثم انسداد حاقن جزئيا. هذا تسد إما أن يمنع أو يحول الحقن. هذا أيضا يمكن معالجتها بسهولة (ملاحظة على الخطوة 2.4.8). ينبغي للمرء أن ترغب في microinject في حين أن الحيوان هو في إطار التجسيمي هناك ثلاثة بدائل. أولا، يمكن للمرء أن زيادة طول طوق microinjector بحيث يمكن عقد بحزم إلى جانب تتلاعب التجسيمي، وكذلك تمديد بعيدا بما فيه الكفاية للسماح للاتصال PE20 أنابيب. ثانيا، علىه يمكن زرع زمنيا قنية واستخدام microinjector القياسية المعروضة هنا. ثالثا، يمكن للمرء أن استخدام المرسومة، والماصات الزجاج المصقول. 16،17 وجود قيود كبير من الإجراء المقدمة هنا هو أن أفضل أجريت في الفئران التعامل معها بشكل جيد والتي هم على دراية الإجراء. الفئران المستخدمة للبيانات الموضحة في قسم النتائج المطلوبة أي إجراءات معالجة خاصة لنفس محقق التعامل مع الفئران على أساس يومي لأكثر من 2 أشهر. وشملت هذه الملاحظة اليومية والتلاعب في عملية الزرع الجراحي لمدة 2 أسابيع على الأقل. ومع ذلك، الفئران يمكن اعتادوا بسرعة عن طريق عدد من التقنيات التي تستخدم لقبل قبل نبض تثبيط الفحص، التي يمكن أن تتأثر الإجهاد. تم هذه التقنيات التعود الخاصة مفصل بشكل جيد في السابق. 43 وبالإضافة إلى هذه الإجراءات، فإنه من المستحسن أن الفئران أن تعود على الإجراء microinjection حيث يتم استخدام microinjectors تقصير دوحلقة حقن &quot;صورية&quot;. خلال هذه الحقن الشام، فمن الأهمية بمكان أن microinjector لا تبرز في الأنسجة من أجل الحد من تلف الأنسجة. وبعبارة أخرى، يجب أن تكون عازمة على microinjector لم يعد من 14 ملم. وهكذا، فإن التعود شامل اللازمة لتنفيذ الأمثل لهذه التقنية يمكن أن ينظر إليه القيد. ورغم وجود العديد من النماذج السلوكية لقياس الدافع، يتم استخدام نسبة التقدمية عادة لقياس جهد أن هذا الموضوع هو على استعداد لبذل للحصول على معزز. وتدريجيا نسبة نموذج تنتج قدرا تعرف باسم نقطة، والتي غالبا ما تعرف بأنها أقصى عدد من المطابع رافعة في نسبة الانتهاء الماضية؛. أي القصوى الاستجابة التي ولدت معزز 21 ونسبة التقدمية حساسة للمعزز الحجم. على سبيل المثال، أعلى الكوكايين (أو السكروز) جرعات ينتج نقطة توقف ارتفاع وانخفاض الكوكايين (أو السكروز) جرعات تسفر عن breakp أقلoint. 21،22 وبناء على ذلك، توقف هو وكيل تستخدم بشكل روتيني لالدافع و / أو تعزيز الفعالية. 21،23-26 لأن القصد من نقطة هي لتحديد متى يتوقف الحيوان الاستجابة، معلمة هامة من نسبة التقدمية النموذج هو طول الدورة. يمكن أطوال جلسة محدود وضع غطاء زائف على القيم نقطة توقف وهذا يمكن أن تتفاقم كل العلاجات السابقة التي تقلل بشكل غير طبيعي معدل الإدارة الذاتية أو أن التوقف زيادة ما بعد التعزيز. هذا الخلط يمكن التغلب على أي عدد من النهج؛. على سبيل المثال، جلسات العمل التي تنتهي عند حجب الحيوان الاستجابة من قبل بعض متعددة من متوسط ​​الفترة الفاصلة بين ضخ 44 A البديل أكثر تطبق عادة لهذا النهج هو إنهاء جلسات عمل مرة واحدة الاستجابة له تم حجب بعض قيمة محددة تجريبيا، والذي يقام ثابت عبر المواضيع. قدمنا ​​طريقة لتطبيق هذا النهج في الخطوة 4.4.9.11.

Rodents and humans respond in remarkably similar ways to behaviorally relevant stimuli1-3. This suggests that rodents are appropriate subjects for elucidating the molecular substrates of behavior and complex psychiatric conditions4. Understanding the molecular substrates of complex behavioral processes, such as motivation, frequently requires brain microinjection. Both the brain microinjection technique and a primary motivation assay will be presented here. Rats will be used as subjects, but these procedures can readily be adapted to well-handled mice. Included herein are procedures for the manufacture of the required cannulae, obturators (dummy cannulae or stylets), and microinjectors. The method presented is significantly more flexible and more cost-efficient than prefabricated implements. This flexibility will prove valuable when optimizing conditions. Importantly, because the microinjection procedure can be used to test a myriad of hypotheses; the techniques presented here should be broadly applicable. For example, receptor ligands can be microinjected to understand neurochemistry3,5,6; cell-permeable peptides and small-molecules can be microinjected to understand intracellular signaling pathways7-10; toxins, ion channel blockers, or antagonist cocktails can be microinjected to understand circuitry1,11,12.
While the generic protocol presented here can be readily adapted by the user for their particular needs, the procedure is particularly well suited for behavioral assays since microinjection occurs in awake rodents that are only under mild hand restraint. No anesthesia or special restraints are required. This is possible because the brain itself lacks pain sensation. However, if anesthesia is not used, microinjection must occur through cannulae that were previously stereotaxically implanted. This is because nociceptors are present on the scalp, meninges,13 which are the membranes surrounding the brain, and the periosteum,14 which is the membrane covering the skull. It should be noted that microinjection under anesthesia is sometimes desirable. One example is when the virus is being injected, and one may wish to inject virus directly through either stainless steal needles15 or glass pipettes because this can reduce tissue damage and improve transduction efficiency.16,17 The microinjectors described below can be modified for this purpose and suggestions on how to do this can be found in the Discussion. Because other JoVE articles have demonstrated stereotaxic brain cannula implantation,18-20 these procedures will not be covered here.
We present these microinjection procedures together with an assay that quantifies motivation. Several rodent models of motivated behavior are currently in use, such as the runway box and barrier scaling. Here, we describe how to use an operant progressive ratio schedule of reinforcement to quantify motivation where operant responding is being maintained by a reinforcer. Responding on the progressive ratio is responsive to reinforcer magnitude.21,22 Accordingly, this assay is routinely used as a proxy for motivation and/or reinforcing efficacy. 21,23-30 Because several excellent reviews have covered this topic in detail,21,24 we will focus mainly on practical concerns.

<table border="0" cellpadding="0" cellspacing="0">
	<tbody>
		<tr>
			<td>Cannula Tubing</td>
			<td>Amazon Supply/ Small Parts</td>
			<td>HTXX-26T-60</td>
			<td>26 gauge, Hypotube S/S 316-TW 26GA</td>
		</tr>
		<tr>
			<td>Obturator</td>
			<td>Amazon Supply/ Small Parts</td>
			<td>GWXX-0080-30-05</td>
			<td>33 gauge, Wire S/S 316LVM 0.008 IN</td>
		</tr>
		<tr>
			<td>Microinjector Wire</td>
			<td>MicroGroup</td>
			<td>33RW 304</td>
			<td>33 gauge</td>
		</tr>
		<tr>
			<td>Super Glue</td>
			<td>Loctite</td>
			<td>3924AC</td>
			<td>Liquid, Non-gel, can be autoclaved</td>
		</tr>
		<tr>
			<td>Microinjector Plastic Tubing</td>
			<td>Becton Dickson</td>
			<td>427406</td>
			<td>PE20</td>
		</tr>
		<tr>
			<td>Medium Weight Hemostats</td>
			<td>World Precision Instruments</td>
			<td>501241-G</td>
			<td></td>
		</tr>
		<tr>
			<td>Ruler</td>
			<td>Fisher</td>
			<td>09-016</td>
			<td>150 mm</td>
		</tr>
		<tr>
			<td>#7 Forceps</td>
			<td>Stoelting</td>
			<td>52100-77</td>
			<td>Dumont, Dumostar</td>
		</tr>
		<tr>
			<td>Rotary Tool</td>
			<td>Dremmel</td>
			<td>285</td>
			<td>Two-speeds</td>
		</tr>
		<tr>
			<td>Cut-off Disc</td>
			<td>McMaster Carr</td>
			<td>3602</td>
			<td>15/16&#34; x 0.025&#34;</td>
		</tr>
		<tr>
			<td>Microinjection Pump</td>
			<td>Harvard Apparatus</td>
			<td>PhD 2000</td>
			<td></td>
		</tr>
		<tr>
			<td>1 ul Glass Syringe</td>
			<td>Hamilton</td>
			<td>7001KH</td>
			<td>Needle Style: 25s/2.75&#34;/3</td>
		</tr>
		<tr>
			<td>Cotton Tipped Applicator</td>
			<td>Fisher</td>
			<td>23-400-101</td>
			<td></td>
		</tr>
		<tr>
			<td>Lab Wipes</td>
			<td>Kimwipes</td>
			<td>34133</td>
			<td></td>
		</tr>
		<tr>
			<td>Operant Software</td>
			<td>Coulbourn</td>
			<td>Graphic State</td>
			<td></td>
		</tr>
		<tr>
			<td>Operant Chambers</td>
			<td>Coulborun</td>
			<td>Habitest</td>
			<td></td>
		</tr>
	</tbody>
</table>

rodent brain microinjection to study molecular substrates of motivated behavior

Brain microinjection can aid elucidation of the molecular substrates of complex behaviors, such as motivation. For this purpose rodents can serve as appropriate models, partly because the response to behaviorally relevant stimuli and the circuitry parsing stimulus-action outcomes is astonishingly similar between humans and rodents. In studying molecular substrates of complex behaviors, the microinjection of reagents that modify, augment, or silence specific systems is an invaluable technique. However, it is crucial that the microinjection site is precisely targeted in order to aid interpretation of the results. We present a method for the manufacture of surgical implements and microinjection needles that enables accurate microinjection and unlimited customizability with minimal cost. Importantly, this technique can be successfully completed in awake rodents if conducted in conjunction with other JoVE articles that covered requisite surgical procedures. Additionally, there are many behavioral paradigms that are well suited for measuring motivation. The progressive ratio is a commonly used method that quantifies the efficacy of a reinforcer to maintain responding despite an (often exponentially) increasing work requirement. This assay is sensitive to reinforcer magnitude and pharmacological manipulations, which allows reinforcing efficacy and/ or motivation to be determined. We also present a straightforward approach to program operant software to accommodate a progressive ratio reinforcement schedule.

نحن هنا توضيح أمثلة من النتائج التي يمكن الحصول عليها مع الإجراء أعلاه. عرض لأول مرة هي منطقة النموذجية التي يتم transfected بواسطة ناقلات فيروسية (الشكل 3). بشكل عام، يتم الحصول على حجم transfected من ~ 1 مم 3 في أنسجة الجسم المخطط. حجم المنطقة transfected يمكن قياسها كميا عبر مسلسل أقسام باستخدام طريقة كافاليري في 32 الأهم من ذلك أن حجم transfected يعتمد على العديد من العوامل مثل نوع من الأنسجة التي transfected؛ المصلي الفيروسي. المروج. معدل وحجم حقن. عدد الجسيمات حقن. injectate درجة الحموضة. وعما إذا كان الكواشف فرط، مثل مانيتول، استخدمت. 33،34 عادة، ونحن microinject 10 12 الجسيمات / مل، 1 ميكرولتر / الجانب أكثر من 10 دقيقة، والسماح 7 دقيقة إضافية قبل استبدال obturators. بالإضافة إلى ذلك، injectate عموما حول درجة الحموضة 8. التالي، وتبين لنا أن الدافع يمكن التلاعب بها من قبل أي من التعبير التحوير (الشكل 4)أو الدوائية microinjection كاشف (الشكل 5). في الشكل (4)، أعربنا عن مستقبلات مصمم المنشط حصريا من قبل مصمم المخدرات (DREADDs). وأعقب المنطقة الترميز مستقبلات DREADD قبل دخول موقع الريبوسوم الداخلية وكاسيت mCitrine. وmCitrine يسمح التصور مناسب من الخلايا المصابة بالعدوى بالنقل. وقد رافق DREADD إلى heterotrimeric G-بروتين Gαq. تفعيل DREADD Gαq الديناميكي يمكن أن تحفز الخلايا النجمية، 28،35 وDREADD نفسها يمكن تفعيلها من خلال الإدارة الشاملة للكلوزابين-N-أكسيد (CNO، 3 ملغ / كغ، والملكية الفكرية). وقد تم تدريب 14،22،36 الجرذان ل رافعة تستجيب لتعزيز الايثانول، حيث حققت 3 المطابع رافعة 1 فرصة للشرب يوميا خلال جلسات ساعة 1 أكثر من 60 يوما متواصلة. بعد ذلك، اضطر الفئران إلى الامتناع عن ممارسة الجنس، وأعرب عن DREADDs Gαq الديناميكي في النواة المتكئة النجمية الأساسية. بعد 3 الامتناع الاسبوع، والدافع لADMI الذاتي<html> وقد تم قياس nister الإيثانول عن طريق نقطة. 21،27-30 تفعيل النواة المتكئة النجمية الأساسية، عن طريق إدارة CNO النظامية، وانخفاض الدافع من الفئران لاستئناف الإيثانول الإدارة الذاتية بعد الامتناع عن ممارسة الجنس مقارنة مع السيارة. الأهم من ذلك، كان CNO أي تأثير في فوج المدربين على حد سواء أن كان يعبر عن البروتين الفلوري الأخضر بدلا من DREADD. <img alt="الشكل (3)" src="/files/ftp_upload/53018/53018fig3.jpg" /> الشكل 3. ممثل منطقة الجسم المخطط البطني transfected بفيروس microinjected. توضح هذه الصورة منطقة النواة المتكئة الخلايا النجمية التي و transfected باتباع الأسلوب أعلاه. وطبع البيانات من بول وآخرون 13 بإذن من صاحب حقوق الطبع والنشر. يمكن الاطلاع على التفاصيل في هذا المنشور والمواد التكميلية المرفقة.على بياض &quot;&gt; الرجاء انقر هنا لعرض نسخة أكبر من هذا الرقم. <img alt="الرقم 4" src="/files/ftp_upload/53018/53018fig4.jpg" /> تم تخفيض الرقم 4. الدافع من الفئران لإدارة الذات الايثانول من خلال تفعيل التحوير الذي كان الإفراط في المعبر عنها في النواة المتكئة النجمية الأساسية. تم microinjected الفيروسات والدافع قياس عبر نقطة بعد السماح أسبوع واحد للفيروس للتعبير. أعرب التحوير ومصمم مستقبلات المنشط حصريا من قبل مصمم المخدرات (DREADDs). A-اتجاه واحد ANOVA (F (2،30) = 3.29، P = 0.04) تليها شفيه بعد خاصة كشفت أن تفعيل DREADD من قبل الإدارة الشاملة للكلوزابين-N-أكسيد (CNO، 3 ملغ / كغ، والملكية الفكرية ) إلى خفض كبير في تحفيز الفئران لإدارة الذات الإيثانول بعد الامتناع عن ممارسة الجنس مقابل سيارة كان CNO أي تأثير في فوج المدربين على حد سواء أن كان يعبر عن البروتين الفلوري الأخضر (GFP) بدلا من DREADD. وطبع البيانات من بول وآخرون 13 بإذن من صاحب حقوق الطبع والنشر. يمكن الاطلاع على التفاصيل في هذا المنشور والمواد التكميلية المرفقة. <img alt="الرقم 5" src="/files/ftp_upload/53018/53018fig5.jpg" /> الرقم 5. Microinjection من الفجوة حاصرات تقاطع زيادة الحافز من الفئران في تقرير المصير، إدارة الإيثانول بعد الامتناع عن ممارسة الجنس قيمت اثنين من حاصرات الفجوة تقاطع للتأثير على الدافع (قياس عبر نقطة) من الفئران في تقرير المصير، إدارة الإيثانول: ميفلوكين و18- ألفا glycyrrhetinic حمض (18-α). وكشفت ذات اتجاهين ANOVA التي Microinjection من حاصرات الفجوة تقاطع في النواة المتكئة زاد الأساسية الدافع من الفئران في تقرير المصير، إدارة الإيثانول بعد الامتناع عن ممارسة الجنس (F (3،40) = 5.56، P = 0.003). وطبع البيانات من بول وآخرون 13 بإذن من صاحب حقوق الطبع والنشر. يمكن الاطلاع على التفاصيل في هذا المنشور والمواد التكميلية المرفقة.

Watch this Scientific Journal Video about Rodent Brain Microinjection to Study Molecular Substrates of Motivated Behavior at JoVE.com

Rodent Brain Microinjection to Study Molecular Substrates of Motivated Behavior

Rodents are an appropriate model to investigate the molecular substrates of behavior and complex psychiatric disorders. Brain microinjection in awake rodents can be used to elucidate disease substrates. An efficient and customizable brain microinjection method as well as the execution of an operant paradigm that quantifies motivation is presented.

القوارض الدماغ Microinjection لدراسة ركائز الجزيئي للسلوك الدوافع

Brain microinjection can aid elucidation of the molecular substrates of complex behaviors, such as motivation. For this purpose rodents can serve as ...

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JoVE Journal

Behavior

14.2K Views.  Virginia Commonwealth University School of Medicine. Rodents are an appropriate model to investigate the molecular substrates of behavior and complex psychiatric disorders. Brain microinjection in awake rodents can be used to elucidate disease substrates. An efficient and customizable brain microinjection method as well as the execution of an operant paradigm that quantifies motivation is presented. 

Video: Rodent Brain Microinjection to Study Molecular Substrates of Motivated Behavior

Stereotaxic Microinjection of Viral Vectors Expressing Cre Recombinase to Study the Role of Target Genes in Cocaine Conditioned Place Preference

Microinjecting recombinant adenoassociated viral (rAAV) vectors expressing Cre recombinase into distinct mouse brain regions to selectively knockout genes of interest allows for enhanced temporally- and regionally-specific control of gene deletion, compared to existing methods. While conditional deletion can also be achieved by mating mice that express Cre recombinase under the control of specific gene promoters with mice carrying a floxed gene, stereotaxic microinjection allows for targeting of discrete brain areas at experimenter-determined time points of interest. In the context of cocaine conditioned place preference, and other cocaine behavioral paradigms such as self-administration or psychomotor sensitization that can involve withdrawal, extinction and/or reinstatement phases, this technique is particularly useful in exploring the unique contribution of target genes to these distinct phases of behavioral models of cocaine-induced plasticity. Specifically, this technique allows for selective ablation of target genes during discrete phases of a behavior to test their contribution to the behavior across time. Ultimately, this understanding allows for more targeted therapeutics that are best able to address the most potent risk factors that present themselves during each phase of addictive behavior.

This article describes how to microinject viral vectors into mouse brain and then test in a conditioned place preference paradigm that includes an acquisition, extinction and reinstatement phase.

حقن مكروي التجسيمي من ناقلات فيروسية وإذ تعرب عن لجنة المساواة العرقية recombinase البكتيري المحور إلى دراسة دور الجينات المستهدفة في الكوكايين مكيفة مكان ميول

Microinjecting recombinant adenoassociated viral (rAAV) vectors expressing Cre recombinase into distinct mouse brain regions to selectively knockout genes ...

Uncovering Beat Deafness: Detecting Rhythm Disorders with Synchronized Finger Tapping and Perceptual Timing Tasks

A set of behavioral tasks for assessing perceptual and sensorimotor timing abilities in the general population (i.e., non-musicians) is presented here with the goal of uncovering rhythm disorders, such as beat deafness. Beat deafness is characterized by poor performance in perceiving durations in auditory rhythmic patterns or poor synchronization of movement with auditory rhythms (e.g., with musical beats). These tasks include the synchronization of finger tapping to the beat of simple and complex auditory stimuli and the detection of rhythmic irregularities (anisochrony detection task) embedded in the same stimuli. These tests, which are easy to administer, include an assessment of both perceptual and sensorimotor timing abilities under different conditions (e.g., beat rates and types of auditory material) and are based on the same auditory stimuli, ranging from a simple metronome to a complex musical excerpt. The analysis of synchronized tapping data is performed with circular statistics, which provide reliable measures of synchronization accuracy (e.g., the difference between the timing of the taps and the timing of the pacing stimuli) and consistency. Circular statistics on tapping data are particularly well-suited for detecting individual differences in the general population. Synchronized tapping and anisochrony detection are sensitive measures for identifying profiles of rhythm disorders and have been used with success to uncover cases of poor synchronization with spared perceptual timing. This systematic assessment of perceptual and sensorimotor timing can be extended to populations of patients with brain damage, neurodegenerative diseases (e.g., Parkinson&#8217;s disease), and developmental disorders (e.g., Attention Deficit Hyperactivity Disorder).

Behavioral tasks that allow for the assessment of perceptual and sensorimotor timing abilities in the general population (i.e., non-musicians) are presented. Synchronization of finger tapping to the beat of an auditory stimuli and detecting rhythmic irregularities provides a means of uncovering rhythm disorders.

كشف بيت الصمم: اضطرابات كشف إيقاع مع فنجر تزامن التنصت والمهام الإدراكية التوقيت

A set of behavioral tasks for assessing perceptual and sensorimotor timing abilities in the general population (i.e., non-musicians) is presented here ...

A Dual Task Procedure Combined with Rapid Serial Visual Presentation to Test Attentional Blink for Nontargets

When viewers search for targets in a rapid serial visual presentation (RSVP) stream, if two targets are presented within about 500 msec of each other, the first target may be easy to spot but the second is likely to be missed. This phenomenon of attentional blink (AB) has been widely studied to probe the temporal capacity of attention for detecting visual targets. However, with the typical procedure of AB experiments, it is not possible to examine how the processing of non-target items in RSVP may be affected by attention. This paper describes a novel dual task procedure combined with RSVP to test effects of AB for nontargets at varied stimulus onset asynchronies (SOAs). In an exemplar experiment, a target category was first displayed, followed by a sequence of 8 nouns. If one of the nouns belonged to the target category, participants would respond &#8216;yes&#8217; at the end of the sequence, otherwise participants would respond &#8216;no&#8217;. Two 2-alternative forced choice memory tasks followed the response to determine if participants remembered the words immediately before or after the target, as well as a random word from another part of the sequence. In a second exemplar experiment, the same design was used, except that 1) the memory task was counterbalanced into two groups with SOAs of either 120 or 240 msec and 2) three memory tasks followed the sequence and tested remembrance for nontarget nouns in the sequence that could be anywhere from 3 items prior the target noun position to 3 items following the target noun position. Representative results from a previously published study demonstrate that our procedure can be used to examine divergent effects of attention that not only enhance targets but also suppress nontargets. Here we show results from a representative participant that replicated the previous finding.&#160;

This paper describes a novel dual task procedure combined with Rapid Serial Visual Presentation to look at attentional blink at varied stimulus onset asynchronies. This experimental procedure differed from others in that it tested attentional blink for nontargets.

إجراء العمل المزدوج السريع جنبا إلى جنب مع عرض مرئي المسلسل لاختبار سيكلوجية الإنتباه الطرفة لNontargets

When viewers search for targets in a rapid serial visual presentation (RSVP) stream, if two targets are presented within about 500 msec of each other, the ...

Using the Activity-based Anorexia Rodent Model to Study the Neurobiological Basis of Anorexia Nervosa

Anorexia nervosa (AN) is a psychiatric illness characterized by excessively restricted caloric intake and abnormally high levels of physical activity. A challenging illness to treat, due to the lack of understanding of the underlying neurobiology, AN has the highest mortality rate among psychiatric illnesses. To address this need, neuroscientists are using an animal model to study how neural circuits may contribute toward vulnerability to AN and may be affected by AN. Activity-based anorexia (ABA) is a bio-behavioral phenomenon described in rodents that models the key symptoms of anorexia nervosa. When rodents with free access to voluntary exercise on a running wheel experience food restriction, they become hyperactive &#8211; running more than animals with free access to food. Here, we describe the procedures by which ABA is induced in adolescent female C57BL/6 mice. On postnatal day 36 (P36), the animal is housed with access to voluntary exercise on a running wheel. After 4 days of acclimation to the running wheel, on P40, all food is removed from the cage. For the next 3 days, food is returned to the cage (allowing animals free food access) for 2 hr daily. After the fourth day of food restriction, free access to food is returned and the running wheel is removed from the cage to allow the animals to recover. Continuous multi-day analysis of running wheel activity shows that mice become hyperactive within 24 hr following the onset of food restriction. The mice run even during the limited time during which they have access to food. Additionally, the circadian pattern of wheel running becomes disrupted by the experience of food restriction. We have been able to correlate neurobiological changes with various aspects of the animals&#8217; wheel running behavior to implicate particular brain regions and neurochemical changes with resilience and vulnerability to food-restriction induced hyperactivity.

Here we present a protocol to induce activity-based anorexia (ABA) in female adolescent mice. ABA is a condition of hyperactivity evoked by imposing food restriction on rodents with access to a running wheel. This phenomenon is being used as a model to study the underlying neurobiology of anorexia nervosa.

باستخدام القائم على آخر فقدان الشهية القوارض نموذج لدراسة أساس العصبية من فقدان الشهية العصبي

Anorexia nervosa (AN) is a psychiatric illness characterized by excessively restricted caloric intake and abnormally high levels of physical activity. A ...

Combined Shuttle-Box Training with Electrophysiological Cortex Recording and Stimulation as a Tool to Study Perception and Learning

Shuttle-box avoidance learning is a well-established method in behavioral neuroscience and experimental setups were traditionally custom-made; the necessary equipment is now available by several commercial companies. This protocol provides a detailed description of a two-way shuttle-box avoidance learning paradigm in rodents (here Mongolian gerbils; Meriones unguiculatus) in combination with site-specific electrical intracortical microstimulation (ICMS) and simultaneous chronical electrophysiological in vivo recordings. The detailed protocol is applicable to study multiple aspects of learning behavior and perception in different rodent species.
Site-specific ICMS of auditory cortical circuits as conditioned stimuli here is used as a tool to test the perceptual relevance of specific afferent, efferent and intracortical connections. Distinct activation patterns can be evoked by using different stimulation electrode arrays for local, layer-dependent ICMS or distant ICMS sites. Utilizing behavioral signal detection analysis it can be determined which stimulation strategy is most effective for eliciting a behaviorally detectable and salient signal. Further, parallel multichannel-recordings using different electrode designs (surface electrodes, depth electrodes, etc.) allow for investigating neuronal observables over the time course of such learning processes. It will be discussed how changes of the behavioral design can increase the cognitive complexity (e.g. detection, discrimination, reversal learning).

Shuttle-box avoidance learning is well-established in behavioral neuroscience. This protocol describes how shuttle-box learning in rodents can be combined with site-specific electrical intracortical microstimulation (ICMS) and simultaneous chronical in vivo recordings as a tool to study multiple aspects of learning and perception.

جنبا إلى جنب المكوك بوكس ​​التدريب مع الكهربية اللحاء تسجيل وتحفيز كأداة لدراسة الإدراك والتعلم

Shuttle-box avoidance learning is a well-established method in behavioral neuroscience and experimental setups were traditionally custom-made; the ...

The Rodent Psychomotor Vigilance Test (rPVT): A Method for Assessing Neurobehavioral Performance in Rats and Mice

The human Psychomotor Vigilance Test (PVT) is a widely used procedure for measuring changes in fatigue and sustained attention. The present article describes a rodent version of the PVT&#8212;termed the &#34;rPVT&#34;&#8212;that measures similar aspects of attention (i.e., performance accuracy, motor speed, premature responding, and lapses in attention). Data are presented that demonstrate both the short- and long-term usefulness of the rPVT when employed with laboratory rats. Rats easily learn the rPVT, and learning to perform the basic procedure takes less than two weeks of training. Once acquired, rat performances in the rPVT show a high degree of similarity to these same performance measures in the human PVT, including similarities in, lapses in attention, reaction times, vigilance decrements across session time (i.e., the human &#34;time-on-task&#34; effects), and the response-stimulus interval (RSI) effect described for humans. Thus the rPVT can be an extremely valuable tool for assessing the effects of a wide range of variables on sustained attention quite similar to human PVT performances, and thus can be useful for developing novel treatments for neurobehavioral dysfunctions.

The Rodent Psychomotor Vigilance Test rPVT: A Method for Assessing Neurobehavioral Performance in Rats and Mice

A rat version of the human Psychomotor Vigilance Test (PVT) is described that measures aspects of attention similar to those measured with the human PVT, including aspects of human vigilance such as performance accuracy, motor speed, premature responding, and lapses in attention.

القوارض النفسي اليقظة اختبار (rPVT): طريقة لتقييم السلوك العصبي الأداء في الجرذان والفئران

The human Psychomotor Vigilance Test (PVT) is a widely used procedure for measuring changes in fatigue and sustained attention. The present article ...

Reversible Cooling-induced Deactivations to Study Cortical Contributions to Obstacle Memory in the Walking Cat

On complex, naturalistic terrain, sensory information about an environmental obstacle can be used to rapidly adjust locomotor movements for avoidance. For example, in the cat, visual information about an impending obstacle can modulate stepping for avoidance. Locomotor adaptation can also occur independent of vision, as sudden tactile inputs to the leg by an expected obstacle can modify the stepping of all four legs for avoidance. Such complex locomotor coordination involves supraspinal structures, such as the parietal cortex. This protocol describes the use of reversible, cooling-induced cortical deactivation to assess parietal cortex contributions to memory-guided obstacle locomotion in the cat. Small cooling loops, known as cryoloops, are specially shaped to deactivate discrete regions of interest to assess their contributions to an overt behavior. Such methods have been used to elucidate the role of parietal area 5 in memory-guided obstacle avoidance in the cat.

Complex locomotion in naturalistic environments requiring careful coordination of the limbs involves regions of the parietal cortex. The following protocol describes the use of reversible cooling-induced deactivation to demonstrate the role of parietal area 5 in memory-guided obstacle avoidance in the walking cat.

ديكتيفاتيونس عكسها المستحثة بالتبريد لدراسة المساهمات القشرية للذاكرة عقبة في القط المشي

On complex, naturalistic terrain, sensory information about an environmental obstacle can be used to rapidly adjust locomotor movements for avoidance. For ...

Central and Divided Visual Field Presentation of Emotional Images to Measure Hemispheric Differences in Motivated Attention

Two dominant theories on lateralized processing of emotional information exist in the literature. One theory posits that unpleasant emotions are processed by right frontal regions, while pleasant emotions are processed by left frontal regions. The other theory posits that the right hemisphere is more specialized for the processing of emotional information overall, particularly in posterior regions.
Assessing the different roles of the cerebral hemispheres in processing emotional information can be difficult without the use of neuroimaging methodologies, which are not accessible or affordable to all scientists. Divided visual field presentation of stimuli can allow for the investigation of lateralized processing of information without the use of neuroimaging technology. 
This study compared central versus divided visual field presentations of emotional images to assess differences in motivated attention between the two hemispheres. The late positive potential (LPP) was recorded using electroencephalography (EEG) and event-related potentials (ERPs) methodologies to assess motivated attention. Future work will pair this paradigm with a more active behavioral task to explore the behavioral impacts on the attentional differences found.

This study compared central versus divided visual field presentations of emotional images to assess differences in motivated attention between the two hemispheres. The late positive potential (LPP) was recorded using electroencephalography (EEG) and event-related potentials (ERPs) methodologies to assess motivated attention.

عرض المجال البصري المركزي وتقسيم الصور العاطفية لقياس الاختلافات نصف الكرة الغربي بدافع الاهتمام

Two dominant theories on lateralized processing of emotional information exist in the literature. One theory posits that unpleasant emotions are processed ...

Combining Quantitative Food-intake Assays and Forcibly Activating Neurons to Study Appetite in Drosophila

Food consumption is under the tight control of the brain, which integrates the physiological status, palatability, and nutritional contents of the food, and issues commands to start or stop feeding. Deciphering the processes underlying the decision-making of timely and moderate feeding carries major implications in our understanding of physiological and psychological disorders related to feeding control. Simple, quantitative, and robust methods are required to measure the food ingestion of animals after experimental manipulation, such as forcibly increasing the activities of certain target neurons. Here, we introduced dye-labeling-based feeding assays to facilitate the neurogenetic study of feeding control in adult fruit flies. We review available feeding assays, and then describe our methods step-by-step from setup to analysis, which combine thermogenetic and optogenetic manipulation of neurons controlling feeding motivation with dye-labeled food intake assay. We also discuss the advantages and limitations of our methods, compared with other feeding assays, to help readers choose an appropriate assay.

Combining Quantitative Food-intake Assays and Forcibly Activating Neurons to Study Appetite in Drosophila

Quantitative food-intake assays with dyed food provide a robust and high-throughput means to evaluate feeding motivation. Combining the food consumption assay with thermogenetic and optogenetic screens is a powerful approach to investigate the neural circuits underlying appetite in adult Drosophila melanogaster.

الجمع بين تناول الطعام الكمية فحوصات وتنشيط الخلايا العصبية لدراسة الشهية في المورفولوجية قسراً

Food consumption is under the tight control of the brain, which integrates the physiological status, palatability, and nutritional contents of the food, ...

Stress-Enhanced Fear Learning, a Robust Rodent Model of Post-Traumatic Stress Disorder

Fear behaviors are important for survival, but disproportionately high levels of fear can increase the vulnerability for developing psychiatric disorders such as post-traumatic stress disorder (PTSD). To understand the biological mechanisms of fear dysregulation in PTSD, it is important to start with a valid animal model of the disorder. This protocol describes the methodology required to conduct stress-enhanced fear learning (SEFL) experiments, a preclinical model of PTSD, in both rats and mice. SEFL was developed to recapitulate critical aspects of PTSD, including long-term sensitization of fear learning caused by an acute stressor. SEFL uses aspects of Pavlovian fear conditioning but produces a distinct and robust sensitized fear response far greater than normal conditional fear responses. The trauma procedure involves placing a rodent in a conditioning chamber and administering 15 unsignaled shocks randomly distributed over 90 minutes (for rat experiments; for mouse experiments, 10 unsignaled shocks randomly distributed over 60 minutes are used). On day 2, rodents are placed in a novel conditioning context where they receive a single shock; then, on day 3 they are placed back in the same context as on day 2 and tested for changes in freezing levels. Rodents that previously received the trauma display enhanced levels of freezing on the test day compared to those that received no shocks on the first day. Thus, with this model, a single highly stressful experience (the trauma) produces extreme fear of the stimuli associated with the traumatic event.

Here we describe the detailed methodology required to conduct stress-enhanced fear learning (SEFL) experiments, a preclinical model of post-traumatic stress disorder, in both rats and mice. The model utilizes aspects of Pavlovian fear conditioning and freezing as an index of enhanced fear in rodents.

الخوف الإجهاد--تعزيز التعلم، نموذج القوارض قوية من اضطراب الإجهاد اللاحق للصدمة النفسية

Fear behaviors are important for survival, but disproportionately high levels of fear can increase the vulnerability for developing psychiatric disorders ...