The authors would like to thank Theresa Jones, Ph.D. for her guidance and assistance in adapting the reaching task to mice. Data presented in this manuscript were supported by grants from NIH-NINDS (NS64586 to TAJ and NS076275 to ALK) and a predoctoral NRSA to KAT (F31AG034032). The NIH was not involved in any aspect of study designs or analyses presented in this manuscript nor in the composition of this manuscript.

以下のメソッドは、テキサス大学オースティン校とイリノイウェズリアン動物管理使用委員会によって承認されたプロトコルに準拠しています。これは、研究者が手袋を着用するか、いずれかの実験動物で行動訓練に従事した場合に適切な予防措置（前後に手を洗う）を取るのどちらかことをお勧めします。手術のためのとの間に備えて、動物を取り扱う際には手袋を着用しなければならない。 1。慣れ食品制限 NOTE：PMRTは欲求タスクであるように、それが到達応答を動機付けし、トレーニングセッション中に満腹感を防ぐために、従来の訓練の開始に供給するの量およびタイミングを制限することが有益である。 <ol><li>前のタスクの訓練の開始に少なくとも1週間に開始制限給餌スケジュールにマウスを置きます。自由摂食量を確立する前に食物制限の開始に各マウスを計量し、目のように決定される制限給餌の初日に各動物のEの重み。 <ol><li> （ 例えば 、ケージ内に収容された4匹のマウスが存在する場合、ケージは毎日の食事の10グラムを受信します）一日あたりのげっ歯類用の標準食の各マウスの受信〜2.5グラムで、一日一回マウスを養う。給餌は毎日同じ時間に発生したことを確認し、好ましくは同時に、毎日のトレーニングセッションを締結することが期待されている。 </li><li>まだマウスは、それらの自由給餌重量の10％以上を失っていないことを保証するために定期的に動物を秤量する。注：適切な体重維持を促進するためにそれに応じて毎日の食事量を調整します。彼らが成熟するようにしたマウスは、通常、一定の食事制限マウスはPMRT訓練/評価の期間中、食事制限に残っていてもして、体重が増える。 </li></ol></li><li>ホームケージ内のパスタの小さな断片（1.6 cmのカット）に動物をさらす新しいもの嫌いの応答を克服するために事前の訓練を数回。注：通常の露出の5-10日は、マウスproviあたり約4個で十分である各給餌でDED。 </li><li>カミソリの刃を使用して、サイ​​ズ（3.2センチメートル）にパスタの部分をカット。注：これは、パスタ片の過剰前日のトレーニングや密閉容器に格納されている未使用の部分を始めにカットされることをお勧めします。カッペリーニパスタは、行列を埋めるために使用されている。パスタの異なるブランドが行列やパスタを破るマウスのために必要な力の量のパスタの安定性に影響を与える可能性がある、食感、直径が異なるように、DeCeccoブランドのパスタは、トレーニングとテスト全体で使用することをお勧めします。 </li><li>マトリックス（ 図1A）で使用可能なすべての穴を埋める、パスタマトリックスに未調理カッペリーニパスタピースを置きます。 </li><li>前に置かれた完全なパスタマトリックス（ 図1A）と試験室の底に食べるパスタのいくつかの部分を検査室にマウスを慣らす。 5〜10分の3セッションのためにマウスを慣らす。注：マウスはhabitua中にパスタのために達することを奨励すべきではありませんTiONからトレーニング。マウスには、通常開口部を通ってそれを盗聴によって到達室の外に位置パスタに興味を示し始める。それは、必要に応じて、単一のチャンバ内の2ケージの仲間を慣らすことは可能であるが、マウスは個々に成形され、訓練を受けなければならない。各動物の行動装置内に配置される前と後のすべての表面を70％エタノールまたは類似の、安全な消毒液で洗浄する必要があります。 </li></ol> 2。シェーピングリーチ<ol><li> 3-5一日一回の成形試験を介してリーチを成形することにより、各動物の優先手足を決定します。最初に発生する10分または10時間の合計のために達するために、マウスを許可します。 <ol><li>馴化訓練（ 図1A）のように、チャンバの前で完全なパスタマトリックスと検査室で個別にマウスを置きます。 </li><li>別々に左右の手足と流域の数を示す、各肢に達した回数を記録します。拡張機能としてリーチを定義する手首室の平面を壊すようなことに達する開口部を通って手足の;リーチに向け又はパスタと接触することがすることが必要ではない。 </li></ol></li><li>到達には消極的であるマウスを奨励するために達する開口部を通ってちょうどチャンバー内のパスタのいくつかの部分を持ってください。マウスは、このように後退パスタ片の後に到達するためにそれらを奨励し、興味（ 例えばスニッフィング、噛む）を示していたときのパスタの部分を引き出す。マウスは、最初は乾燥パスタに興味を示していない場合は、それらを口に合うようにするために暖かい水の小さなカップパスタ片の先端を濡らす。 </li><li>マウスは単一肢との日々の流域の70％以上を示す場合に四肢の好みを決定します。これはタスク17に到達する訓練部分の間に観察学習の量を制限することができるように、終わっていない形の動物にやる。マウスが成形された後PMRTトレーニングを開始します。注：トレーニング次第NEXとして起動することができますTの日ですが、整形および訓練手順の間に数日待つようにしても良い。 </li></ol> 3届かトレーニング<ol><li>列車のマウスPMRTに能力を確立するために、以前の侮辱に一日一回。注：各試験はいずれか早い方15分以上（成功と失敗）観測者によってカウント100に達すると、最大構成されています。マウスを好みの手足のみで到達するために訓練されています。より激しいトレーニングパラダイムが18望む場合マウスは一日あたり2つの試験に耐えます。 <ol><li>フロント（ 図1B）に配置されたハーフフルマトリックスと試験チャンバー内にマウスを置きます。列車のマウスは、マウスは自分の体の正中線を越え達するため好ましい肢に行列反対側のみを充填することにより、好みの手足のみ到達する。 Sではないであろう（この四肢とリーチの試みを阻止するために、満たされていない、好まざる四肢に対応する行列の部分を残すuccessful彼らはパスタを達成）、好ましい手足だけ到達し奨励することができないため。 </li></ol></li><li>それは、マウスが正常に初期のトレーニングセッションの間に作品を打破するために行列にある間、パスタに少量の圧力を置きます。マウス用のパスタの部分を壊さないでください。軽く背後に垂直な意図、目標到達に1つまたは2つのパスタ片を保持することによってこれを達成する。サポートのこの小さな量は、彼らが最初にタスクを学んでいるようにマウスが把握するための非常に柔軟かつ困難である細いパスタを安定化するのに役立ちます。 </li><li>到達し、成功に達するの数、成功した流域の位置の合計数を記録します。成功に達するには、開口部を通って到達パスタの部分をつかむと、行列から削除するには、パスタピースを破るために、マウスが必要です。注：パスタ片は試験が終了した後までの行列で置き換えられるべきではありません。初期のトレーニングでは、マウスに、多くのパスタ片を壊すことはありません。 </li><li>安定した性能（日にわたってせいぜい2より多くのまたはより少ない部分でパスタの少なくとも9個を壊す）の（5日まで）は、少なくとも3日間として定義されている能力にPMRT列車マウス。それは多くの場合、習熟度に若い成体マウスを訓練するために、15〜20の間で日かかります。 </li></ol> 4。少ない - 患肢トレーニング<ol><li> （優先/影響を受けたとless-affected/unpreferred手足に明確化については図2を参照）が好ましい到達肢に反対運動皮質への虚血発作後4日から始まるあまり影響を受けた四肢（ すなわち 、手術前、好まざる四肢を）訓練。 1日1回15分または100リーチトレーニングセッションを管理します。 <ol><li>成功していない初期の患肢に到達することを確実にするために、あまり影響を受けた四肢のトレーニングの第一週をパスタの最初の列（到達開口から延びるすなわち 、最も内側の垂直列）を取り外します。 </li><li&gt;置く前に配置されたハーフ満たされたマトリックスと到達チャンバー中のマウス。行列の満たされた半分は今ではあまり影響を受けた（好まざる）四肢に到達するために、マウスを強制的に手術前の満たされた半分の反対であることを確認してください。 </li></ol></li><li>到達開口部を通って、この手足の延長を強化し、あまり影響を受けた四肢に到達奨励する。マウスは到達室の床の上にパスタの小さい（1/2個）に関係なく、リーチが成功したか否かの訓練所の最初の数日間で、あまり影響を受けた四肢を拡張する。 </li><li> 100リーチ合計に向かってあまり患肢で作られたものだけが到達を数える。流域の総数に向けた患肢とひそか試行をカウントされません。 </li><li>あまり影響を受けた四肢の訓練の最初の7日後に行列にパスタの最も内側の縦の列を返します。 </li><li>到達し、成功に達するの数、およびSUCCの場所の数を記録しますessful届きます。注：これらのデータは、あまり影響を受けた肢でパターンに到達するの違いを観察するために分析することができるが、以前に報告されていない。 </li></ol> 5。到達分析あまり影響を受けた四肢の訓練を次PMRTタスクに影響を受けた四肢を評価することにより、影響を受けた四肢の機能の回復にはあまり影響を受けた四肢使用の影響を判別します。あまり影響を受けた四肢のトレーニング日数所望の数（通常14日）完了した後、この評価が発生します。 <ol><li> （優先手足いっぱいに反対行列の半分、 すなわち ）訓練手順とまったく同じ指向室の前で行列を配置します。注：これは彼らの影響を受けた（以前推奨）手足に到達するためにマウスを強制します。 </li><li>プレストローク性能レベルと比較する達すると、成功に達するの数、成功した流域の位置の合計数を記録します。のパフォーマンスを調査しないでくださいこれらの影響を受けた四肢のプローブとしてあまり影響を受けた四肢のトレーニング中に患肢は患肢の回復に影響を与える可能性があるトレーニングセッションとして機能することができる。 </li></ol>

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Neurosci. 124 (1), 124-132 (2010).</li><li>Tennant, K. 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=Skill+learning+induced+plasticity+of+motor+cortical+representations+is+time+and+age-dependent.">Skill learning induced plasticity of motor cortical representations is time and age-dependent.</a> Neurobiol. Learn. Mem. 98 (3), 291-302 (2012).</li><li>Mathers, C. D., Boerma, T., Fat, D. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Global+and+regional+causes+of+death.">Global and regional causes of death.</a> Br. Med. Bull. 92 (1), 7-32 (2009).</li><li>Go, A. S., 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=Heart+disease+and+stroke+statistics--2013+update:+a+report+from+the+American+Heart+Association.">Heart disease and stroke statistics--2013 update: a report from the American Heart Association.</a> Circulation. 127 (1), (2013).</li><li>Clarke, J., Mala, H., Windle, V., Chernenko, G., Corbett, D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+Effects+of+Repeated+Rehabilitation+"Tune-Ups"+on+Functional+Recovery+After+Focal+Ischemia+in+Rats.">The Effects of Repeated Rehabilitation "Tune-Ups" on Functional Recovery After Focal Ischemia in Rats.</a> Neurorehabil. Neural Repair. 23 (9), 886-894 (2009).</li><li>Adkins, D. L., Voorhies, A. C., Jones, T. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Behavioral+and+neuroplastic+effects+of+focal+endothelin-1+induced+sensorimotor+cortex+lesions.">Behavioral and neuroplastic effects of focal endothelin-1 induced sensorimotor cortex lesions.</a> Neuroscience. 128 (3), 473-486 (2004).</li><li>Bryant, A., Bernier, B., Jones, T. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Abnormalities+in+skilled+reaching+movements+are+improved+by+peripheral+anesthetization+of+the+less-affected+forelimb+after+sensorimotor+cortical+infarcts+in+rats.">Abnormalities in skilled reaching movements are improved by peripheral anesthetization of the less-affected forelimb after sensorimotor cortical infarcts in rats.</a> Behav. Brain Res. 177 (2), 298-307 (2007).</li><li>Whishaw, I. Q., Coles, B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Varieties+of+paw+and+digit+movement+during+spontaneous+food+handling+in+rats:+Postures,+bimanual+coordination,+preferences,+and+the+effect+of+forelimb+cortex+lesions.">Varieties of paw and digit movement during spontaneous food handling in rats: Postures, bimanual coordination, preferences, and the effect of forelimb cortex lesions.</a> Behav. Brain Res. 77 (1-2), 135-148 (1996).</li><li>Whishaw, I. Q., Dringenberg, H. C., Pellis, S. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Spontaneous+Forelimb+Grasping+in+Free+Feeding+by+Rats+-+Motor+Cortex+Aids+Limb+and+Digit+Positioning.">Spontaneous Forelimb Grasping in Free Feeding by Rats - Motor Cortex Aids Limb and Digit Positioning.</a> Behav. Brain Res. 48 (2), 113-125 (1992).</li><li>Horie, N., Maag, A., Hamilton, S. A., Shichinohe, H., Bliss, T. M., Steinberg, G. K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Mouse+model+of+focal+cerebral+ischemia+using+endothelin-1.">Mouse model of focal cerebral ischemia using endothelin-1.</a> J. Neurosci. Methods. 173 (2), 286-290 (2008).</li><li>Maldonado, M. A., Allred, R. P., Felthauser, E. L., Jones, T. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Motor+skill+training,+but+not+voluntary+exercise,+improves+skilled+reaching+after+unilateral+ischemic+lesions+of+the+sensorimotor+cortex+in+rats.">Motor skill training, but not voluntary exercise, improves skilled reaching after unilateral ischemic lesions of the sensorimotor cortex in rats.</a> Neurorehabil. Neural Repair. 22 (3), 250-261 (2008).</li><li>Clarkson, A. N., Lopez-Valdes, H. E., Overman, J. J., Charles, A. C., Brennan, K. C., Carmichael, S. T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Multimodal+examination+of+structural+and+functional+remapping+in+the+mouse+photothrombotic+stroke+model.">Multimodal examination of structural and functional remapping in the mouse photothrombotic stroke model.</a> Journal of Cerebral Blood Flow and Metabolism. 33 (5), 716-723 (2013).</li><li>Liu, Z., Chopp, M., Ding, X., Cui, Y., Li, Y. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Axonal+remodeling+of+the+corticospinal+tract+in+the+spinal+cord+contributes+to+voluntary+motor+recovery+after+stroke+in+adult+mice.">Axonal remodeling of the corticospinal tract in the spinal cord contributes to voluntary motor recovery after stroke in adult mice.</a> Stroke. 44 (7), 1951-1956 (2013).</li></ol>

The authors have nothing to disclose.

PMRTマウス業者に達する性能を評価するための簡単​​な、定量的な方法を表しています。時間がかかるが、それは少数のトレーニングセッションと信頼性と再現性のあるデータを収集するように訓練される以前に経験のない大学生が可能である。タスクは、虚血性傷害3、13、15以下のマウス運動技能の性能のわずかな変化を測定するのに十分に敏感であり、それであるため多くの研?...

マウスモデルは、部分的には、その利便性と手頃な価格だけでなく、他のアプリケーション間でのin vivoイメージングに適しているトランスジェニック系統の利用可能性の実験的脳卒中研究のために、ますます人気となっている。これは、実験モデルで人気を増加して、損傷後の機能的な結果の敏感な行動評価の開発に関心が1-7増加している。人間の脳卒中生存者によって使用される両方のリハビリと代償戦略を模倣する動物の訓練プロトコルの開発に成功し、診療所8で使用する実験動物研究からの調査結果を変換する機能を向上させます。タスク（PMRT）に達するパスタマトリックス上運動技能訓練は、これまで感覚運動皮質3の虚血発作、次の運動技能の結果の敏感な行動評価として確立されている。 主要な関心の一つ脳卒中研究の懸念リハビリと傷害後の機能回復の改善を促進する行動戦略の開発と理解のS。現在、ヒトでのリハビリテーションの戦略は不完全リカバリ8になる。また、リハビリテーションセラピストは完全に彼らの影響を受けた四肢（S）の機能を回復する能力を損なう可能性脳卒中生存者は回復中に開発代償戦略を戦う必要があります。例えば、上肢機能に影響を与える一方的脳卒中後の、人間がそれらの低い影響肢9,10への依存を発症する傾向がある。短期間で機能する人の能力を向上させるが、これは、患肢の非使用学ん動物モデル11-13に示されたように、最終的な回復の可能性を妨げることがあります。動物ではこれらの知見は、ヒトの14に制約誘発性運動療法の開発と使用を知らせるために貢献している。動物モデルはbeneficiaです研究者が補助する神経生物学的メカニズムを探索し、機能の回復を促進させることにより、リハビリテーション戦略を改善するためのlである。脳卒中後の機能の効果的な行動評価であることに加えて、PMRTは、感覚運動ストローク15以下の改善された機能的結果を促進するのに有効なリハビリテーション戦略として確立されている。 PMRTも効果的に模倣患肢の不使用を学んだので、過度の依存の少ない患肢13の初期にもかかわらず、機能回復を改善することが、行動の操作への洞察を提供するために使用することができます。 PMRTの構築は3以前に記載されている。簡単に説明すると、到達室が開放された上部と下部で（20センチ長さ15cm、8.5センチ幅）4プレキシガラスの壁で構成されている。働き室の前壁の下部ベースから延びる中心スリット（13センチと幅5mm）がある達する開口部（ 図1A）として得た。パスタマトリックスは完全にブロックの深さを通して掘削直径1mmの穴を大型プラスチックブロック（5センチ幅8.5センチメートル長、及び1.5センチ）。 260穴の合計が各ホール（ 図1B）との間に2ミリメートルに達したウィンドウから2ミリメートルを開始、があります。パスタマトリックスは、乾燥、垂直に配向パスタ片が露出パスタ片の約半分を有するマトリックス段の深さ全体を通って延びるように設計されている。オーバーヘッドプラスチックや厚紙の取り外し可能な部分は、大きさに切断し、マトリックスの下側にしっかりとテープで固定する必要があります。これは、輸送中のマトリックスから脱落パスタ片を防止し、壊れたパスタ片の容易な除去を可能にする。 PMRTは、正確な結果データを収集し、臨床的な現象を模倣するために四肢の使用を操作することを可能にする実験者汎用性と敏感な行動アッセイである。行動Oのようなutcome対策、PMRTは実験者がより正確に梗塞サイズ3、16の伝統的な尺度の場合よりもリハビリ戦略の有効性を反映した行動データを収集することができます。行動操作など、PMRTは実験者がマウスでの上肢の使用を制御することができますリハビリテーションの臨床経験を模倣するために（ すなわち 、患肢の訓練）または不使用を学んだ（ つまり、あまり影響を受けた四肢のトレーニング）。神経解剖学の方法と組み合わせることで、PMRTは、脳卒中後の代償四肢使用を次の関数や不適応行動の可塑性の回復をサポートするメカニズムを探索する機会を研究者に提供します。 PMRTはさらに、外傷性脳損傷などの脳損傷および上肢障害の他のマウスモデルに適用することができる。 PMRTの別の利点は、その手頃な価格である。タスクに必要な機器の家にかなり合理的に構築することができ、データ収集はないスペースや財源を大量に必要とし、タスクが確実にデータを収集するために、学部学生のための非常に簡単ではありません。さらに、PMRTが少しでも行動障害3、13に敏感です。このプロトコルは、損傷後の行動回復を促進し、運動技能の学習を評価するための簡単で効果的な方法を提供し、模倣は脳卒中の確立マウスモデルにおいて不使用現象を学びました。

<table border="0" cellpadding="0" cellspacing="0" width="794">
	<tbody>
		<tr height="42">
			<td height="42" style="height:42px;width:216px;">Name of Material/ Equipment</td>
			<td style="width:71px;">Company</td>
			<td style="width:119px;">Catalog Number</td>
			<td style="width:388px;">Comments/Description</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">Reaching Chamber</td>
			<td style="width:71px;"></td>
			<td style="width:119px;"></td>
			<td>Reaching chambers are made in house with Plexiglas</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">Pasta Matrix Block</td>
			<td style="width:71px;"></td>
			<td style="width:119px;"></td>
			<td>The Pasta Matrix box is made in house using a heavy plastic block</td>
		</tr>
		<tr height="63">
			<td height="63" style="height:63px;width:216px;">Capellini Pasta</td>
			<td style="width:71px;">DeCecco</td>
			<td style="width:119px;"></td>
			<td style="width:388px;">DeCecco brand capellini pasta can be purchased in a grocery store or through an online retailer such as Amazon</td>
		</tr>
	</tbody>
</table>

compensatory limb use and behavioral assessment of motor skill learning following sensorimotor cortex injury in a mouse model of ischemic stroke

マウスモデルは、行動神経科学の分野で、具体的には、実験的な脳卒中の研究でますます人気となっている。モデル予めとしては、マウスに特異的な感受性の行動策を開発することが重要である。この議定書は、脳卒中のマウスモデルで使用するために熟練した運動課題について説明しています。パスタマトリックスは、正確な結果データを収集し、代償戦略（ すなわち 、不使用を学んだ）し、リハビリトレーニングを当て含むヒト臨床的現象を模倣するために四肢使用を操作する実験者が許可汎用性と高感度の行動分析などのタスク機能に達する。神経解剖学のツールと​​組み合わせることで、この作業には、脳卒中後の機能（またはその欠如）の行動回復をサポートするメカニズムを探求する研究者を許可します。タスクは、FUに関する数多くの研究課題のためのトレーニングとテストのさまざまなオプションを提供して、簡単かつ手頃な価格に設定することと行動の両方で損傷後nctional成果。タスクは、脳卒中のマウスモデルに適用されているが、それはまた、他の上肢損傷モデルにおける機能的転帰の研究において有益であり得る。

PMRT分析の結果は、壊れたパスタ片の数と成功に達するのパターンを含める必要があります。感覚運動皮質病変を有するマウスから得られた結果は、 図3Aに示されたように虚血発作は、成功に達するの数だけでなく、物理的なリーチパターン3、19の両方に影響を与えることを示している。代表パターンの変化は、図3Bに観察することができる。マウスにおける...

Watch this Scientific Journal Video about Compensatory Limb Use and Behavioral Assessment of Motor Skill Learning Following Sensorimotor Cortex Injury in a Mouse Model of Ischemic Stroke at JoVE.com

Compensatory Limb Use and Behavioral Assessment of Motor Skill Learning Following Sensorimotor Cortex Injury in a Mouse Model of Ischemic Stroke

Mouse models have become increasingly popular in studies of behavioral neuroscience. As models advance, it is important to develop sensitive behavioral measures specific to the mouse. This protocol describes the Pasta Matrix Reaching Task, which is a skilled motor task for use in mouse models of stroke.

代償四肢使用および虚血性脳卒中のマウスモデルにおける感覚皮質損傷後の運動技能の学習の行動評価

Mouse models have become increasingly popular in the field of behavioral neuroscience, and specifically in studies of experimental stroke. As models ...

compensatory-limb-use-behavioral-assessment-motor-skill-learning

Research

JoVE Journal

Behavior

11.4K ビュー.  Illinois Wesleyan University. Mouse models have become increasingly popular in studies of behavioral neuroscience. As models advance, it is important to develop sensitive behavioral measures specific to the mouse. This protocol describes the Pasta Matrix Reaching Task, which is a skilled motor task for use in mouse models of stroke.

ビデオ: Compensatory Limb Use and Behavioral Assessment of Motor Skill Learning Following Sensorimotor Cortex Injury in a Mouse Model of Ischemic Stroke

Assessment of Sensorimotor Function in Mouse Models of Parkinson's Disease

Sensitive and reliable behavioral outcome measures are essential to the evaluation of potential therapeutic treatments in preclinical trials for many neurodegenerative diseases. In Parkinson's disease, sensorimotor tests sensitive to varying degrees of nigrostriatal dysfunction are fundamental for testing the efficacy of potential therapeutics. Reliable and quite elegant sensorimotor measures exist for rats, however many of these tests measure sensorimotor asymmetry within the rat and are not entirely suitable for the newer genetic mouse models of PD. We have put together a battery of sensorimotor tests inspired by the sensitive tests in rats and adapted for mice. The test battery highlighted in this study is chosen for a) its sensitivity in a wide variety of mouse models of PD, b) its ease in implementing into a study, and c) its low expense. These tests have proven useful in characterizing novel genetic mouse models of PD as well as in testing potential disease-modifying therapies.

In Parkinson's disease and movement disorders in general, sensitive and reliable behavioral assays are essential for testing novel potential therapeutics. Here, we describe a manageable battery of sensorimotor tests for mice that are sensitive to varying degrees of injury to the nigrostriatal system and useful for preclinical studies.

パーキンソン病のマウスモデルにおける感覚運動機能の評価

Sensitive and  reliable behavioral outcome measures are essential to the evaluation of  potential therapeutic treatments in preclinical trials for many  ...

行動学

Study Motor Skill Learning by Single-pellet Reaching Tasks in Mice

Reaching for and retrieving objects require precise and coordinated motor movements in the forelimb. When mice are repeatedly trained to grasp and retrieve food rewards positioned at a specific location, their motor performance (defined as accuracy and speed) improves progressively over time, and plateaus after persistent training. Once such reaching skill is mastered, its further maintenance does not require constant practice. Here we introduce a single-pellet reaching task to study the acquisition and maintenance of skilled forelimb movements in mice. In this video, we first describe the behaviors of mice that are commonly encountered in this learning and memory paradigm, and then discuss how to categorize these behaviors and quantify the observed results. Combined with mouse genetics, this paradigm can be utilized as a behavioral platform to explore the anatomical underpinnings, physiological properties, and molecular mechanisms of learning and memory.

Persistent practice improves the precision of coordinated movements.&#160;Here we introduce a single-pellet reaching task, which is designed to assess the learning and memory of forelimb skill in mice.&#160;

マウスのシングル·ペレット到達タスクで学ぶ学習運動スキル

Reaching for and retrieving objects require precise and coordinated motor movements in the forelimb. When mice are repeatedly trained to grasp and ...

Behavioral Assessment of the Aging Mouse Vestibular System

Age related decline in balance performance is associated with deteriorating muscle strength, motor coordination and vestibular function. While a number of studies show changes in balance phenotype with age in rodents, very few isolate the vestibular contribution to balance under either normal conditions or during senescence. We use two standard behavioral tests to characterize the balance performance of mice at defined age points over the lifespan: the rotarod test and the inclined balance beam test. Importantly though, a custom built rotator is also used to stimulate the vestibular system of mice (without inducing overt signs of motion sickness). These two tests have been used to show that changes in vestibular mediated-balance performance are present over the murine lifespan. Preliminary results show that both the rotarod test and the modified balance beam test can be used to identify changes in balance performance during aging as an alternative to more difficult and invasive techniques such as vestibulo-ocular (VOR) measurements.

Motor control and balance performance are known to deteriorate with age. This paper presents a number of standard noninvasive behavioral tests with the addition of a simple rotary stimulus to challenge the vestibular system and show changes in balance performance in a murine model of aging.

高齢マウス前庭系の行動評価

Age related decline in balance performance is associated with deteriorating muscle strength, motor coordination and vestibular function. While a number of ...

Experimental Assessment of Mouse Sociability Using an Automated Image Processing Approach

Mouse is the preferred model organism for testing drugs designed to increase sociability. We present a method to quantify mouse sociability in which the test mouse is placed in a standardized apparatus and relevant behaviors are assessed in three different sessions (called session I, II, and III).
The apparatus has three compartments (see Figure 1), the left and right compartments contain an inverted cup which can house a mouse (called &#34;stimulus mouse&#34;).
In session I, the test mouse is placed in the cage and its mobility is characterized by the number of transitions made between compartments. In session II, a stimulus mouse is placed under one of the inverted cups and the sociability of the test mouse is quantified by the amounts of time it spends near the cup containing the enclosed stimulus mouse vs. the empty inverted cup. In session III, the inverted cups are removed and both mice interact freely. The sociability of the test mouse in session III is quantified by the number of social approaches it makes toward the stimulus mouse and by the number of times it avoids a social approach by the stimulus mouse.
The automated evaluation of the movie detects the nose of the test mouse, which allows the determination of all described sociability measures in session I and II (in session III, approaches are identified automatically but classified manually). To find the nose, the image of an empty cage is digitally subtracted from each frame of the movie and the resulting image is binarized to identify the mouse pixels. The mouse tail is automatically removed and the two most distant points of the remaining mouse are determined; these are close to nose and base of tail. By analyzing the motion of the mouse and using continuity arguments, the nose is identified.
<img alt="Figure 1" src="/files/ftp_upload/52508/52508fig1.jpg" /> 
Figure 1. Assessment of Sociability During 3 sessions. Session I (top): Acclimation of test mouse to the cage. Session II (middle): Test mouse moving freely in the cage while the stimulus mouse is enclosed in an inverted cup. Session III (bottom): Both test mouse and stimulus mouse are allowed to move freely and interact with each other.

This protocol describes a method to quantify mouse sociability. Mice are videotaped as they move and interact in a special cage. Movie processing allows for the automated quantification of sociability with excellent accuracy and reliability.

自動画像処理手法を用いてマウス社交性の実験的評価

Mouse is the preferred model organism for testing drugs designed to increase sociability. We present a method to quantify mouse sociability in which the ...

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.

知覚と学習を研究するためのツールと​​しての電気生理学的皮質の記録と刺激と組み合わせたシャトル・ボックストレーニング

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

Vagus Nerve Stimulation as a Tool to Induce Plasticity in Pathways Relevant for Extinction Learning

Extinction describes the process of attenuating behavioral responses to neutral stimuli when they no longer provide the reinforcement that has been maintaining the behavior. There is close correspondence between fear and human anxiety, and therefore studies of extinction learning might provide insight into the biological nature of anxiety-related disorders such as post-traumatic stress disorder, and they might help to develop strategies to treat them. Preclinical research aims to aid extinction learning and to induce targeted plasticity in extinction circuits to consolidate the newly formed memory. Vagus nerve stimulation (VNS) is a powerful approach that provides tight temporal and circuit-specific release of neurotransmitters, resulting in modulation of neuronal networks engaged in an ongoing task. VNS enhances memory consolidation in both rats and humans, and pairing VNS with exposure to conditioned cues enhances the consolidation of extinction learning in rats. Here, we provide a detailed protocol for the preparation of custom-made parts and the surgical procedures required for VNS in rats. Using this protocol we show how VNS can facilitate the extinction of conditioned fear responses in an auditory fear conditioning task. In addition, we provide evidence that VNS modulates synaptic plasticity in the pathway between the infralimbic (IL) medial prefrontal cortex and the basolateral complex of the amygdala (BLA), which is involved in the expression and modulation of extinction memory.

Vagus nerve stimulation (VNS) has emerged as a tool to induce targeted synaptic plasticity in the forebrain to modify a range of behaviors. This protocol describes how to implement VNS to facilitate the consolidation of fear extinction memory.

ツールとしての迷走神経刺激は、絶滅の学習のための関連経路の可塑性を誘導するために

Extinction describes the process of attenuating behavioral responses to neutral stimuli when they no longer provide the reinforcement that has been ...

Investigating Motor Skill Learning Processes with a Robotic Manipulandum

Skilled reaching tasks are commonly used in studies of motor skill learning and motor function under healthy and pathological conditions, but can be time-intensive and ambiguous to quantify beyond simple success rates. Here, we describe the training procedure for reach-and-pull tasks with ETH Pattus, a robotic platform for automated forelimb reaching training that records pulling and hand rotation movements in rats. Kinematic quantification of the performed pulling attempts reveals the presence of distinct temporal profiles of movement parameters such as pulling velocity, spatial variability of the pulling trajectory, deviation from midline, as well as pulling success. We show how minor adjustments in the training paradigm result in alterations in these parameters, revealing their relation to task difficulty, general motor function or skilled task execution. Combined with electrophysiological, pharmacological and optogenetic techniques, this paradigm can be used to explore the mechanisms underlying motor learning and memory formation, as well as loss and recovery of function (e.g. after stroke).

A paradigm is presented for training and analysis of an automated skilled reaching task in rats. Analysis of pulling attempts reveals distinct subprocesses of motor learning.

ロボットマニピュランダムに運動スキルの学習過程を調査

Skilled reaching tasks are commonly used in studies of motor skill learning and motor function under healthy and pathological conditions, but can be ...

Using a Split-belt Treadmill to Evaluate Generalization of Human Locomotor Adaptation

Understanding the mechanisms underlying locomotor learning helps researchers and clinicians optimize gait retraining as part of motor rehabilitation. However, studying human locomotor learning can be challenging. During infancy and childhood, the neuromuscular system is quite immature, and it is unlikely that locomotor learning during early stages of development is governed by the same mechanisms as in adulthood. By the time humans reach maturity, they are so proficient at walking that it is difficult to come up with a sufficiently novel task to study de novo locomotor learning. The split-belt treadmill, which has two belts that can drive each leg at a different speed, enables the study of both short- (i.e., immediate) and long-term (i.e., over minutes-days; a form of motor learning) gait modifications in response to a novel change in the walking environment. Individuals can easily be screened for previous exposure to the split-belt treadmill, thus ensuring that all experimental participants have no (or equivalent) prior experience. This paper describes a typical split-belt treadmill adaptation protocol that incorporates testing methods to quantify locomotor learning and generalization of this learning to other walking contexts. A discussion of important considerations for designing split-belt treadmill experiments follows, including factors like treadmill belt speeds, rest breaks, and distractors. Additionally, potential but understudied confounding variables (e.g., arm movements, prior experience) are considered in the discussion.

We describe a protocol for investigating human locomotor adaptation using the split-belt treadmill, which has two belts that can drive each leg at a different speed. We specifically focus on a paradigm designed to test the generalization of adapted locomotor patterns to different walking contexts (e.g., gait speeds, walking environments).

分割トレッドミルを使用した運動適応の一般化の評価

Understanding the mechanisms underlying locomotor learning helps researchers and clinicians optimize gait retraining as part of motor rehabilitation. ...

Detecting Behavioral Deficits in Rats After Traumatic Brain Injury

With the increasing incidence of traumatic brain injury (TBI) in both civilian and military populations, TBI is now considered a chronic disease; however, few studies have investigated the long-term effects of injury in rodent models of TBI. Shown here are behavioral measures that are well-established in TBI research for times early after injury, such as two weeks, until two months. Some of these methods have previously been used at later times after injury, up to one year, but by very few laboratories. The methods demonstrated here are a short neurological assessment to test reflexes, a Beam-Balance to test balance, a Beam-Walk to test balance and motor coordination, and a working memory version of the Morris water maze that can be sensitive to deficits in reference memory. Male rats were handled and pre-trained to neurological, balance, and motor coordination tests prior to receiving parasagittal fluid percussion injury (FPI) or sham injury. Rats can be tested on the short neurological assessment (neuroscore), the beam-balance, and the Beam-Walk multiple times, while testing on the water maze can only be done once. This difference is because rats can remember the task, thus confounding the results if repeated testing is attempted in the same animal. When testing from one to three days after injury, significant differences are detected in all three non-cognitive tasks. However, differences in the Beam-Walk task were not detectable at later time points (after 3 months). Deficits were detected at 3 months in the Beam-Balance and at 6 months in the neuroscore. Deficits in working memory were detected out to 12 months after injury, and a deficit in a reference memory first appeared at 12 months. Thus, standard behavioral tests can be useful measures of persistent behavioral deficits after FPI.

The goal of the behavioral tests presented here is to detect functional deficits in rats after traumatic brain injury. Four specific tests are presented that detect deficits in behaviors to reflect the damage to specific brain areas at times extending to one year after injury.

外傷性脳損傷後のラットの行動の赤字を検出

With the increasing incidence of traumatic brain injury (TBI) in both civilian and military populations, TBI is now considered a chronic disease; however, ...

The "Motor" in Implicit Motor Sequence Learning: A Foot-stepping Serial Reaction Time Task

This protocol describes a modified serial reaction time (SRT) task used to study implicit motor sequence learning. Unlike the classic SRT task that involves finger-pressing movements while sitting, the modified SRT task requires participants to step with both feet while maintaining a standing posture. This stepping task necessitates whole body actions that impose postural challenges. The foot-stepping task complements the classic SRT task in several ways. The foot-stepping SRT task is a better proxy for the daily activities that require ongoing postural control, and thus may help us better understand sequence learning in real-life situations. In addition, response time serves as an indicator of sequence learning in the classic SRT task, but it is unclear whether response time, reaction time (RT) representing mental process, or movement time (MT) reflecting the movement itself, is a key player in motor sequence learning. The foot-stepping SRT task allows researchers to disentangle response time into RT and MT, which may clarify how motor planning and movement execution are involved in sequence learning. Lastly, postural control and cognition are interactively related, but little is known about how postural control interacts with learning motor sequences. With a motion capture system, the movement of the whole body (e.g., the center of mass (COM)) can be recorded. Such measures allow us to reveal the dynamic processes underlying discrete responses measured by RT and MT, and may aid in elucidating the relationship between postural control and the explicit and implicit processes involved in sequence learning. Details of the experimental set-up, procedure, and data processing are described. The representative data are adopted from one of our previous studies. Results are related to response time, RT, and MT, as well as the relationship between the anticipatory postural response and the explicit processes involved in implicit motor sequence learning.

We introduce the foot-stepping serial reaction time (SRT) task. This modified SRT task, complementing the classic SRT task that involves only finger-pressing movement, better approximates daily sequenced activities and allows researchers to study the dynamic processes underlying discrete response measures and disentangle the explicit process operating in implicit sequence learning.

暗黙的なモーターで「モーター」シーケンス学習: 足ステップのシリアル反応時間のタスク

This protocol describes a modified serial reaction time (SRT) task used to study implicit motor sequence learning. Unlike the classic SRT task that ...