この作品は退役軍人省のリハビリR&Dサービスキャリア開発賞(CDA-1、RX002111;CDA-2;RX002928)からRSA、AJFおよび国立衛生研究所(NIH-NICHD F31 HD097918からDACTおよびNIH-NIEHS T32 ES012870からDACT)およびNEIコアグラントP30EY006360に(

すべての手続きは、アトランタ退役軍人事務施設動物のケアと使用委員会によって承認され、実験動物のケアと使用のための国立衛生研究所ガイドに準拠しました(NIH出版物、第8 版、2011年更新)。
1. オプトモーター応答(OMR)
<ol><li>OMR装置の設定(材料表の装置とソフトウェアの詳細)
	<ol>
<li>げっ歯類に適したサイズのプラットフォーム(マウス、ラット、または大/障害のあるラット)を選択します(図1A)。</li>
		<li>OMRソフトウェアを開き、オプションの複数のタブとOMR/仮想ドラムの内部のライブビデオフィードを持つウィンドウに開く必要があります(図1B)。必要に応じてビデオカメラでズームインまたはズームアウトして、プラットフォームとその周囲を表示します。</li>
		<li>ライブイメージの左側にあるアイコンを確認します(図1C)。緑色のアスタリスクと緑の回転ストライプの両方がライブフィードから消えるように、アスタリスクアイコンと回転ストライプアイコンをクリックします。</li>
		<li>コンパス アイコンをクリックして、緑色の円と 2 本の垂直線が表示されるようにします。緑色の円を伸ばしてプラットフォーム上の黒い円と完全に一致するようにして、OMR が完全に整列するようにします。</li>
		<li>テスト中に円を見る必要がないので、 コンパスアイコン をクリックしてください。 緑色のアスタリスクアイコン と 緑の回転ストライプアイコンを クリックすると、これらのアイコンが再表示されます。緑色のストライプはドラムのストライプと同じ方向に回転し、研究者はストライプの方向を知ることができます。</li>
		<li>[ テスト ] タブをクリックします。[ テスト] の [ 心理物理学 ] タブをクリックします。[ しきい値] で、[ 周波数 ] を選択して空間周波数を測定します。 注: OMR ソフトウェアは、階段パラダイムを使用して、空間周波数 (SF) を自動的に計算します。コントラストは100%に維持されます。</li>
		<li>[ テスト] の [プリセット] タブ を クリックします。Mouse18 または Rat20 のデフォルト設定を選択します。</li>
		<li>[ テスト] の [ ブランキング ] タブをクリックします。マウスが右クリックされるたびにドラム内のコンピュータ画面のストライプ/ブランクを一時停止する [トラッキング 時に空白]ボックスをオンにします。</li>
		<li>[ 結果 ] タブをクリックすると、テストの結果が表示されます。</li>
	</ol></li>
	<li>空間周波数の評価
	<ol>
<li>12°/sの速度でチャンバを周回する垂直正音波格子を示す4台のコンピュータモニタからなるバーチャルリアリティチャンバーの中央にある円形プラットフォーム上にげっ歯類を置きます(図1D)。</li>
		<li>チャンバーの上部に配置されたビデオカメラは、げっ歯類の動作をコンピュータモニターに生き生きと映し出していることに注意してください。</li>
		<li>格子が時計回りまたは反時計回りに移動する場合、げっ歯類の頭による反射的な動作の有無を探します。図示されたバーがプログラムに表示されていることを確認します。<ol>
<li>げっ歯類の頭がグレーティングと同じ方向に動くのを見てください。頭の動きの不安定なバーストではなく、スムーズな追求が起こるまで待って、追跡としてカウントします。</li>
			<li>[ はい ] または [ いいえ ] をクリックします。SF は 0.042 cyc/deg から始まり、各 yes と no を調整して、より簡単または難しくなるようにします(図 1E)。誤って [はい] と [いいえ] をクリックしたためにテストをリセットする必要がある場合は、[ リセット ] をクリックします。</li>
		</ol>
</li>
		<li>げっ歯類がテストされると、げっ歯類の頭の上にアスタリスクを置くようにしてください。 注: これは 2 つの効果があります: 1) 正しい空間周波数を維持します。たとえば、アスタリスクが肩の間に配置されている場合、空間周波数が低くなり、バーが見やすくなり、スコアが誤って高くなります。2)わずかな頭の動きを持つげっ歯類の場合、アスタリスクは、頭が実際に動いているかどうかを測定することが容易になります。</li>
		<li>げっ歯類の空間周波数に達したときにシステムが「完了」と言うのを見てください。 [はい ] ボタンと [いいえ ] ボタンはクリックできなくなります。</li>
		<li>[ 結果 ] タブをクリックすると、左目、右目、および結合された目の空間周波数が表示されます。 注:ソフトウェアは、結果が反転する、すなわち、右目が左目として報告され、左目が右目として報告されるように設定されている場合があります。これは、緑内障モデルで1つの目しか病変していなかったげっ歯類を評価する際に発見された。</li>
	</ol></li>
	<li>コントラスト感度の評価 注: コントラスト感度テストは、空間周波数測定ステップの直後または同じ日または別の日に、空間周波数テストの後にげっ歯類が疲労しているように見える場合に実行できます(コントラスト感度のみをテストする場合は、手順1~2.2に従います)。<ol>
<li>[ テスト ] タブをクリックし、[ 精神物理学 ] タブをクリックします。[ しきい値] で [ コントラスト (単一)] を選択して、コントラスト感度を測定します。</li>
		<li>また、階段パラダイムを使用して、コントラスト感度(CS)曲線のピーク時にSF定数でグレーティングを開始します。これを行うには、[ 刺激 ]タブをクリックし、[ グレーティング ]タブをクリックします。[ 空間周波数 ] ボックスで、ラットの 場合は 0.064 、マウスの場合 は 0.103 と入力します。</li>
		<li>100%からコントラストを開始し、空間周波数テストで見たのと同じ反射的な頭部の動きを探します。試験が進むにつれてコントラストは、げっ歯類が刺激に反応して反射的な頭部の動きを持たなくなるまで減少することに注意してください(図1E)。</li>
		<li>システムが「完了」と表示され、[ はい ]ボタンと [いいえ ]ボタンは、げっ歯類が視覚刺激に応答しなくなり、コントラスト感度のしきい値に達するとクリックできなくなるのを監視します。[ 結果 ]タブをクリックすると、左目、右目、および結合された目のコントラスト感度が表示されます。</li>
	</ol></li>
	<li>テスト後の分析を実行する
	<ol>
<li>両眼が同様の欠損を有すると予想される糖尿病性網膜症の研究では、組み合わせたスコア(左右の目の平均)を分析に使用します。眼に差動損傷を起こすモデル(例えば、爆風損傷や緑内障)については、左右の目のデータを別々に保ちます。</li>
		<li>[空間周波数] では、分析に生のスコア ( [結果 ] タブのデータ) を使用し、これらのスコアをグループ別に平均化します (たとえば、糖尿病、制御など)。</li>
		<li>コントラスト感度の場合、生の値を使用して、以前の画面の輝度の測定とは対照的に、ミッシェルソンのコントラストによって報告されたコントラスト感度を計算します。</li>
	</ol></li>
</ol>2. Y迷路
<ol><li>
テスト用のげっ歯類を準備する
	<ol>
<li>テスト前に30分間、げっ歯類を部屋に適応させろ。 注:研究者はライトをつけたまま部屋に残ることができますが、この間は静かにしてください。</li>
		<li>動物にとって安全な消毒液でY迷路を洗浄し、ペーパータオルですべての消毒液を拭き取ります。迷路が乾燥していることを確認します。</li>
	</ol>
</li>
	<li>
Y迷路を指揮する
	<ol>
<li>Y迷路の初期アームをB、他の2アームをAとCとラベル付けします(図2A)。Y迷路の中心近くの研究者(腕B)に最も近い腕にげっ歯類を1つ置きます。げっ歯類が配置されたら、タイマー( 材料のテーブルで迷路とタイマーの詳細)を開始します。<ol>
<li>各げっ歯類が8分間Y迷路を探索できるようにします。この時間の間に録音を取り、任意の観察をメモします。迷路を視界に入れながら迷路から数フィート離れたところに座り、騒音を出さないようにしてください。</li>
			<li>開始位置を A として記録し、げっ歯類が新しいアームに入るたびに、げっ歯類の新しい位置を記録します(図 2B)。げっ歯類の4つの手足すべてが腕の1つに入っているエントリとして定義します。</li>
			<li>げっ歯類が隠れて迷路の片腕に静止したままにするのを見てください。げっ歯類が60以上同じ場所に残っていて、探索的な行動を示していないように見える場合は、げっ歯類をY迷路の中心に向かって動かし、裁判を続けます。</li>
		</ol>
</li>
		<li>各げっ歯類の後、任意の便を除去し、消毒溶液で迷路をきれいにします。<ol>
<li>すべての消毒液がペーパータオルで拭き取られ、迷路が完全に乾燥していることを確認してから、迷路に次のげっ歯類を置きます。</li>
		</ol>
</li>
	</ol>
</li>
	<li>
自発的な交代と探索的挙動を計算する
	<ol>
<li>探索的動作を 8 分の間に行われたエントリの合計数として計算します。</li>
		<li>自発的な交代によって測定された空間認知を計算する: 成功したオルターネーションの数/(エントリの合計数 - 2)<ol>
<li>げっ歯類が 3 つの異なる場所に順番に移動する際に、正常な交代を定義します (例: ABC、CAB、BCA など)。各正常な切り取りに注意してください(図 2B)。</li>
			<li>動きがACABCABABCABCとして記録された場合、自発的な交代(分母に11の動きがある)を計算する際に、2つの初期の開始位置を無視してください。正確な動きの数を数えます(正確な動き= 8)。パーセント精度を計算します: 8/(13 - 2) = 72.7%</li>
		</ol>
</li>
	</ol>
</li>
</ol>

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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=Daily+visual+stimulation+in+the+critical+period+enhances+multiple+aspects+of+vision+through+BDNF-mediated+pathways+in+the+mouse+retina.">Daily visual stimulation in the critical period enhances multiple aspects of vision through BDNF-mediated pathways in the mouse retina.</a> PLoS One. 13 (2), 0192435 (2018).</li><li>Feola, A. J., 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=Menopause+exacerbates+visual+dysfunction+in+experimental+glaucoma.">Menopause exacerbates visual dysfunction in experimental glaucoma.</a> Experimental Eye Research. 186, 107706 (2019).</li><li>Allen, R. 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=Long-term+functional+and+structural+consequences+of+primary+blast+overpressure+to+the+eye.">Long-term functional and structural consequences of primary blast overpressure to the eye.</a> Journal of Neurotrauma. 35 (17), 2104-2116 (2018).</li><li>Maaswinkel, H., Li, L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Spatio-temporal+frequency+characteristics+of+the+optomotor+response+in+zebrafish.">Spatio-temporal frequency characteristics of the optomotor response in zebrafish.</a> Vision Research. 43 (1), 21-30 (2003).</li><li>Benkner, B., Mutter, M., Ecke, G., M&#252;nch, 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=Characterizing+visual+performance+in+mice:+an+objective+and+automated+system+based+on+the+optokinetic+reflex.">Characterizing visual performance in mice: an objective and automated system based on the optokinetic reflex.</a> Behavioral Neuroscience. 127 (5), 788-796 (2013).</li><li>Lehmann, K., Schmidt, K. F., L&#246;wel, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Vision+and+visual+plasticity+in+ageing+mice.">Vision and visual plasticity in ageing mice.</a> Restorative Neurology and Neuroscience. 30, 161-178 (2012).</li><li>Leinonen, H., Tanila, H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Vision+in+laboratory+rodents-tools+to+measure+it+and+implications+for+behavioral+research.">Vision in laboratory rodents-tools to measure it and implications for behavioral research.</a> Behavioral Brain Research. 352, 172-182 (2018).</li><li>Spielmann, M., Schr&#246;ger, E., Kotz, S. A., Pechmann, T., Bendixen, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Using+a+staircase+procedure+for+the+objective+measurement+of+auditory+stream+integration+and+segregation+thresholds.">Using a staircase procedure for the objective measurement of auditory stream integration and segregation thresholds.</a> Frontiers in Psychology. 4, 534 (2013).</li><li>Shi, C., 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=Optimization+of+optomotor+response-based+visual+function+assessment+in+mice.">Optimization of optomotor response-based visual function assessment in mice.</a> Scientific Reports. 8 (1), 9708 (2018).</li><li>You, M., Yamane, T., Tomita, H., Sugano, E., Akashi, T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+novel+rat+head+gaze+determination+system+based+on+optomotor+responses.">A novel rat head gaze determination system based on optomotor responses.</a> PLoS One. 12 (4), 0176633 (2017).</li><li>Whyte, A. J., 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=Reward-related+expectations+trigger+dendritic+spine+plasticity+in+the+mouse+ventrolateral+orbitofrontal+cortex.">Reward-related expectations trigger dendritic spine plasticity in the mouse ventrolateral orbitofrontal cortex.</a> The Journal of Neuroscience. 39 (23), 4595-4605 (2019).</li></ol>

著者らは開示するものは何もない。

OMRとY迷路は、時間の経過とともにげっ歯類の視覚機能および認知機能の欠損の非侵襲的評価を可能にする。このプロトコルでは、OMRとY迷路が糖尿病のげっ歯類モデルにおける視覚および認知的欠陥を追跡することが実証された。
プロトコルの重要なステップ
ザ OMR
OMRを実行して視覚機能を評価する際に考慮すべき?...

An erratum was issued for:&#160;<a href="https://www.jove.com/t/61806">Behavioral Assessment of Visual Function via Optomotor Response and Cognitive Function via Y-Maze in Diabetic Rats</a>. The author list was updated.
The author list was updated from:
Kaavya Gudapati*1,2, Anayesha Singh*1,3, Danielle Clarkson-Townsend1,4, Andrew J. Feola1,2, Rachael S. Allen1,2 
1Center for Visual and Neurocognitive Rehabilitation, Atlanta VA Medical Center, 
2Department of Biomedical Engineering, Georgia Institute of Technology, 
3Department of Neuroscience, Emory University, 
4Gangarosa Department of Environmental Health, Emory University 
* These authors contributed equally
to:
Kaavya Gudapati*1,2, Anayesha Singh*1,3, Danielle Clarkson-Townsend1,4, Stephen Q. Phillips1, Amber Douglass1, Andrew J. Feola1,2, Rachael S. Allen1,2 
1Center for Visual and Neurocognitive Rehabilitation, Atlanta VA Medical Center, 
2Department of Biomedical Engineering, Georgia Institute of Technology, 
3Department of Neuroscience, Emory University, 
4Gangarosa Department of Environmental Health, Emory University 
* These authors contributed equally

An erratum was issued for:&#160;<a href="https://www.jove.com/t/61806">Behavioral Assessment of Visual Function via Optomotor Response and Cognitive Function via Y-Maze in Diabetic Rats</a>. The author list was updated.

Erratum: Behavioral Assessment of Visual Function via Optomotor Response and Cognitive Function via Y-Maze in Diabetic Rats

4億6,300万人以上の人々が糖尿病と一緒に暮らしており、世界で最大の病気の流行の1つとなっています。糖尿病に起因する重篤な合併症の1つは、アメリカの成人の失明の主な原因である糖尿病性網膜症(DR)である2。今後30年間で、DRのリスクを持つ人口の割合は2倍になると予測されるため、DRの開発を予防し軽減するために、初期段階でDRを診断する新しい方法を見つけることが重要です3。DRは従来、血管疾患4,5,6であると考えられている。しかし、血管病理に先行する神経機能障害とアポトーシスの証拠が現在、DRは神経および血管成分4,5,6,7,8,9を有すると定義されている。DRを診断する1つの方法は、他の神経組織10よりも糖尿病による酸化ストレスや代謝株に対してより脆弱である可能性のある組織であるレティナの神経異常を調べることである。
認知機能と運動機能の低下は、糖尿病でも起こり、しばしば、疾患の変化と相関する。II型糖尿病の高齢者は、ベースライン認知能力の低下を描写し、対照参加者11よりも悪化した認知機能低下を示す。さらに、レティナは中枢神経系の延長として確立されており、病理はretina12に現れる可能性がある。臨床的には、アルツハイマー病および他の疾患の文脈で、レティナと脳の関係は研究されているが、一般的に糖尿病12、13、14、15、16で探索されていない。糖尿病の進行時の脳とレチナの変化は、STZラット(毒素、ストレプトゾトシンまたはSTZが膵臓ベータ細胞に損傷を与えるために使用されるI型糖尿病のモデル)や後頭柿ラット(動物が3週齢頃に高血圧を発症するII型糖尿病のポリジェニックモデル)を含む動物モデルを使用して探索することができる。このプロトコルでは、糖尿病性げっ歯類における認知的および視覚的変化を評価するためのY迷路および眼運動応答についての説明がそれぞれ提供される。光運動応答(OMR)は、各眼17の視覚閾値を測定するために特徴的な反射的なヘッド追跡の動きを監視することによって、空間周波数(視力に似ている)とコントラスト感度を評価します。空間周波数とは、バーの太さまたは細かさを指し、コントラスト感度とは、バーと背景のコントラストの程度を指します(図1E)。一方、Y迷路は、迷路の腕を通して自発的な交代とエントリを通して観察される短期的な空間記憶と探索的機能をテストします。
両方のテストは、目を覚まし、麻酔をしない動物で行われ、動物の生来の応答を利用する利点があり、訓練を必要としないことを意味する。どちらも比較的敏感であり、げっ歯類の糖尿病の進行の早い段階で赤字を検出するために使用することができ、信頼性があり、他の視覚、女性、または行動検査と相関する結果を生み出すという。さらに、OMRとY迷路を電気レチノグラムや光学コヘレンス断層撮影スキャンなどのテストと組み合わせて使用すると、疾患モデルにおいて、レチナル、構造、認知の変化が互いに相対的に発達する時期に関する情報を提供することができます。これらの調査は、糖尿病によって起こる神経退性を同定するのに役立つ可能性がある。最終的には、これは進行の初期段階でDRを効果的に識別する新しい診断方法につながる可能性があります。
このプロトコルの開発に使用されるOMRとY迷路システムは 、材料表に記載されています。OMRに関するこれまでの研究は、プルスキーら18、およびY迷路、モーリスら19によって、このプロトコルを開発するための出発点として使用された。

<table>
	<tbody>
		<tr>
			<td>OptoMotry HD</td>
			<td>CerebralMechanics Inc.</td>
			<td></td>
			<td>OMR apparatus &#38; software</td>
		</tr>
		<tr>
			<td>Timer</td>
			<td>Thomas Scientific</td>
			<td>810029AR</td>
			<td></td>
		</tr>
		<tr>
			<td>Y-Maze apparatus</td>
			<td>San Diego Instruments</td>
			<td>7001-043</td>
			<td>Available specifically for rats</td>
		</tr>
	</tbody>
</table>

behavioral assessment of visual function via optomotor response and cognitive function via y-maze in diabetic rats

視運動応答とY迷路は、それぞれ視覚機能と認知機能を評価するのに有用な行動検査である。検眼応答は、糖尿病性網膜症を含む多くの網膜疾患モデルにおける空間周波数(SF)およびコントラスト感受性(CS)閾値の経時変化を追跡するための貴重なツールです。同様に、Y迷路は、中枢神経系に影響を与える多くの疾患モデルにおける空間認知(自発的な交代によって測定される)および探索的行動(多数のエントリによって測定される)を監視するために使用することができる。光運動応答とY迷路の利点は、感度、テストの速度、自然応答の使用(トレーニングは必要ありません)、および目覚め(非麻酔)動物に実行される能力を含みます。ここでは、オプト運動応答とY迷路の両方についてプロトコルが記載されており、その使用例はI型およびII型糖尿病のモデルに示されている。方法には、げっ歯類や機器の調製、検眼応答とY迷路の性能、および試験後のデータ分析が含まれる。

空間周波数とコントラスト感度のしきい値をげっ歯類から取得できる場合、OMR は成功と見なされます。ここでは、空間周波数を評価するためのOMRの使用は、若い(3-6ヶ月)と高齢者(9-12ヶ月)の両方のナイーブコントロールブラウンノルウェーとロングエバンスラットで示されています。ブラウンノルウェーラットは、典型的には、ロングエバンスラットよりも高いベースライン空間周波数を示?...

Watch this Scientific Journal Video about Behavioral Assessment of Visual Function via Optomotor Response and Cognitive Function via Y-Maze in Diabetic Rats at JoVE.com

Behavioral Assessment of Visual Function via Optomotor Response and Cognitive Function via Y-Maze in Diabetic Rats

糖尿病の結果としての目と脳の両方の神経変性は、げっ歯類に対して行われる行動検査を通じて観察することができる。Y迷路、空間認知の尺度、および視機能の尺度である光運動応答は、両方とも潜在的な診断と治療に関する洞察を提供する。

糖尿病ラットにおけるY-迷路を介した視運動応答と認知機能の行動評価

The optomotor response and the Y-maze are behavioral tests useful for assessing visual and cognitive function, respectively. The optomotor response is a ...

behavioral-assessment-visual-function-via-optomotor-response

Research

JoVE Journal

Behavior

5.4K ビュー.  Atlanta VA Medical Center. 糖尿病の結果としての目と脳の両方の神経変性は、げっ歯類に対して行われる行動検査を通じて観察することができる。Y迷路、空間認知の尺度、および視機能の尺度である光運動応答は、両方とも潜在的な診断と治療に関する洞察を提供する。

ビデオ: Behavioral Assessment of Visual Function via Optomotor Response and Cognitive Function via Y-Maze in Diabetic Rats

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.

Assessment of Sensorimotor Function in Mouse Models of Parkinson&#039;s Disease

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

The Crossmodal Congruency Task as a Means to Obtain an Objective Behavioral Measure in the Rubber Hand Illusion Paradigm

The rubber hand illusion (RHI) is a popular experimental paradigm. Participants view touch on an artificial rubber hand while the participants' own hidden hand is touched. If the viewed and felt touches are given at the same time then this is sufficient to induce the compelling experience that the rubber hand is one's own hand. The RHI can be used to investigate exactly how the brain constructs distinct body representations for one's own body. Such representations are crucial for successful interactions with the external world. To obtain a subjective measure of the RHI, researchers typically ask participants to rate statements such as "I felt as if the rubber hand were my hand". Here we demonstrate how the crossmodal congruency task can be used to obtain an objective behavioral measure within this paradigm.
The variant of the crossmodal congruency task we employ involves the presentation of tactile targets and visual distractors. Targets and distractors are spatially congruent (i.e. same finger) on some trials and incongruent (i.e. different finger) on others. The difference in performance between incongruent and congruent trials - the crossmodal congruency effect (CCE) - indexes multisensory interactions. Importantly, the CCE is modulated both by viewing a hand as well as the synchrony of viewed and felt touch which are both crucial factors for the RHI.
The use of the crossmodal congruency task within the RHI paradigm has several advantages. It is a simple behavioral measure which can be repeated many times and which can be obtained during the illusion while participants view the artificial hand. Furthermore, this measure is not susceptible to observer and experimenter biases. The combination of the RHI paradigm with the crossmodal congruency task allows in particular for the investigation of multisensory processes which are critical for modulations of body representations as in the RHI.

We demonstrate how an objective measure can be employed in the widely employed rubber hand illusion paradigm. This measure is obtained by modifying the well-established crossmodal congruency task. This task allows the investigation of multisensory processes which are critical for modulations of body representations as in the rubber hand illusion.

ラバーハンドイリュージョンパラダイムにおける客観行動測定値を得るための手段としてクロスモーダル一致タスク

The rubber hand illusion (RHI) is a popular experimental paradigm. Participants view touch on an artificial rubber hand while the participants' own hidden ...

Irrelevant Stimuli and Action Control: Analyzing the Influence of Ignored Stimuli via the Distractor-Response Binding Paradigm

Selection tasks in which simple stimuli (e.g. letters) are presented and a target stimulus has to be selected against one or more distractor stimuli are frequently used in the research on human action control. One important question in these settings is how distractor stimuli, competing with the target stimulus for a response, influence actions. The distractor-response binding paradigm can be used to investigate this influence. It is particular useful to separately analyze response retrieval and distractor inhibition effects. Computer-based experiments are used to collect the data (reaction times and error rates). In a number of sequentially presented pairs of stimulus arrays (prime-probe design), participants respond to targets while ignoring distractor stimuli. Importantly, the factors response relation in the arrays of each pair (repetition vs. change) and distractor relation (repetition vs. change) are varied orthogonally. The repetition of the same distractor then has a different effect depending on response relation (repetition vs. change) between arrays. This result pattern can be explained by response retrieval due to distractor repetition. In addition, distractor inhibition effects are indicated by a general advantage due to distractor repetition. The described paradigm has proven useful to determine relevant parameters for response retrieval effects on human action.

The distractor-response binding paradigm is described. It can be used to shed light on the influence irrelevant stimuli, competing with targets for a response, can have on human action. Both response retrieval effects and distractor inhibition effects can be analyzed within the paradigm.

無関係な刺激と行動制御：ディストラクタ - 応答パラダイムを結合することにより無視された刺激の影響を分析

Selection tasks in which simple stimuli (e.g. letters) are presented and a target stimulus has to be selected against one or more distractor stimuli are ...

A Procedure to Observe Context-induced Renewal of Pavlovian-conditioned Alcohol-seeking Behavior in Rats

Environmental contexts in which drugs of abuse are consumed can trigger craving, a subjective Pavlovian-conditioned response that can facilitate drug-seeking behavior and prompt relapse in abstinent drug users. We have developed a procedure to study the behavioral and neural processes that mediate the impact of context on alcohol-seeking behavior in rats. Following acclimation to the taste and pharmacological effects of 15% ethanol in the home cage, male Long-Evans rats receive Pavlovian discrimination training (PDT) in conditioning chambers. In each daily (Mon-Fri) PDT session, 16 trials each of two different 10 sec auditory conditioned stimuli occur. During one stimulus, the CS+, 0.2 ml of 15% ethanol is delivered into a fluid port for oral consumption. The second stimulus, the CS-, is not paired with ethanol. Across sessions, entries into the fluid port during the CS+ increase, whereas entries during the CS- stabilize at a lower level, indicating that a predictive association between the CS+ and ethanol is acquired. During PDT each chamber is equipped with a specific configuration of visual, olfactory and tactile contextual stimuli. Following PDT, extinction training is conducted in the same chamber that is now equipped with a different configuration of contextual stimuli. The CS+ and CS- are presented as before, but ethanol is withheld, which causes a gradual decline in port entries during the CS+. At test, rats are placed back into the PDT context and presented with the CS+ and CS- as before, but without ethanol. This manipulation triggers a robust and selective increase in the number of port entries made during the alcohol predictive CS+, with no change in responding during the CS-. This effect, referred to as context-induced renewal, illustrates the powerful capacity of contexts associated with alcohol consumption to stimulate alcohol-seeking behavior in response to Pavlovian alcohol cues.

A procedure to study the capacity of an alcohol associated environmental context to trigger the renewal of alcohol-seeking behavior in rats is described.

ラットにおけるパブロフ付きアルコール探索行動の状況誘発性のリニューアルを観察する手順

Environmental contexts in which drugs of abuse are consumed can trigger craving, a subjective Pavlovian-conditioned response that can facilitate ...

The Knob Supination Task: A Semi-automated Method for Assessing Forelimb Function in Rats

Tasks that accurately measure dexterity in animal models are critical to understand hand function. Current rat behavioral tasks that measure dexterity largely use video analysis of reaching or food manipulation. While these tasks are easy to implement and are robust across disease models, they are subjective and laborious for the experimenter. Automating traditional tasks or creating new automated tasks can make the tasks more efficient, objective, and quantitative. Since rats are less dexterous than primates, central nervous system (CNS) injury produces more subtle deficits in dexterity, however, supination is highly affected in rodents and crucial to hand function in primates. Therefore, we designed a semi-automated task that measures forelimb supination in rats. Rats are trained to reach and grasp a knob-shaped manipulandum and turn the manipulandum in supination to receive a reward. Rats can acquire the skill within 20 &plusmn; 5 days. While the early part of training is highly supervised, much of the training is done without direct supervision. The task reliably and reproducibly captures subtle deficits after injury and shows functional recovery that accurately reflects clinical recovery curves. Analysis of data is performed by specialized software through a graphical user interface that is designed to be intuitive. We also give solutions to common problems encountered during training, and show that minor corrections to behavior early in training produce reliable acquisition of supination. Thus, the knob supination task provides efficient and quantitative evaluation of a critical movement for dexterity in rats.

This manuscript describes a semi-automated task that quantifies supination in rats. Rats reach, grasp, and supinate a spherical manipulandum. The rat is rewarded with a pellet if the turn angle exceeds a criterion set by the user. This task increases throughput, sensitivity to injury, and objectivity compared to traditional tasks.

ノブ外タスク: ラットの前肢関数を評価するための半自動メソッド

Tasks that accurately measure dexterity in animal models are critical to understand hand function. Current rat behavioral tasks that measure dexterity ...

Simultaneous Recordings of Cortical Local Field Potentials and Electrocorticograms in Response to Nociceptive Laser Stimuli from Freely Moving Rats

Electrocortical responses, elicited by laser heat pulses that selectively activate nociceptive free nerve endings, are widely used in many animal and human studies to investigate the cortical processing of nociceptive information. These laser-evoked brain potentials (LEPs) consist of several transient responses that are time-locked to the onset of laser stimuli. However, the functional properties of the LEP responses are still largely unknown, due to the lack of a sampling technique that can simultaneously record neural activities at the surface of the cortex (i.e., electrocorticogram [ECoG] and scalp electroencephalogram [scalp EEG]) and inside the brain (i.e., local field potential [LFP]). To address this issue, we present here an animal protocol using freely moving rats. This protocol is composed of three main procedures: (1) animal preparation and surgical procedures, (2) a simultaneous recording of ECoG and LFP in response to nociceptive laser stimuli, and (3) data analysis and feature extraction. Specifically, with the help of a 3D-printed protective shell, both ECoG and LFP electrodes implanted on the rat&#39;s skull were securely held together. During data collection, laser pulses were delivered on the rat&#39;s forepaws through gaps in the bottom of the chamber when the animal was in spontaneous stillness. Ongoing white noise was played to avoid the activation of the auditory system by the laser-generated ultrasounds. As a consequence, only nociceptive responses were selectively recorded. Using the standard analytical procedures (e.g., band-pass filtering, epoch extraction, and baseline correction) to extract stimulus-related brain responses, we obtained results showing that LEPs with a high signal-to-noise ratio were simultaneously recorded from ECoG and LFP electrodes. This methodology makes the simultaneous recording of ECoG and LFP activities possible, which provides a bridge of electrocortical signals at the mesoscopic and macroscopic levels, thereby facilitating the investigation of nociceptive information processing in the brain.

We developed a technique that simultaneously records both electrocorticography and local field potentials in response to nociceptive laser stimuli from freely moving rats. This technique helps establish a direct relationship of electrocortical signals at the mesoscopic and macroscopic levels, which facilitates the investigation of nociceptive information processing in the brain.

大脳皮質の局所電界電位と自由行動ラットから侵害受容のレーザー刺激への応答で Electrocorticograms の同時録音

Electrocortical responses, elicited by laser heat pulses that selectively activate nociceptive free nerve endings, are widely used in many animal and ...

Supramaximal Intensity Hypoxic Exercise and Vascular Function Assessment in Mice

Exercise training is an important strategy for maintaining health and preventing many chronic diseases. It is the first line of treatment recommended by international guidelines for patients suffering from cardiovascular diseases, more specifically, lower extremity artery diseases, where the patients' walking capacity is considerably altered, affecting their quality of life. 
Traditionally, both low continuous exercise and interval training have been used. Recently, supramaximal training has also been shown to improve athletes' performances via vascular adaptations, amongst other mechanisms. The combination of this type of training with hypoxia could bring an additional and/or synergic effect, which could be of interest for certain pathologies. Here, we describe how to perform supramaximal intensity training sessions in hypoxia on healthy mice at 150% of their maximal speed, using a motorized treadmill and a hypoxic box. We also show how to dissect the mouse in order to retrieve organs of interest, particularly the pulmonary artery, the abdominal aorta, and the iliac artery. Finally, we show how to perform ex vivo vascular function assessment on the retrieved vessels, using isometric tension studies.

High-intensity training in hypoxia is a protocol that has been proven to induce vascular adaptations potentially beneficial in some patients and to improve athletes&#39; repeated sprint ability. Here, we test the feasibility of training mice using that protocol and identify those vascular adaptations using ex vivo vascular function assessment.

激低酸素運動とマウスの血管機能評価

Exercise training is an important strategy for maintaining health and preventing many chronic diseases. It is the first line of treatment recommended by ...

Investigating the Deployment of Visual Attention Before Accurate and Averaging Saccades via Eye Tracking and Assessment of Visual Sensitivity

This experimental protocol was designed to investigate whether visual attention is obligatorily deployed at the endpoint of saccades. To this end, we recorded the eye position of human participants engaged in a saccade task via eye tracking and assessed visual orientation discrimination performance at various locations during saccade preparation. Importantly, instead of using a single saccade target paradigm for which the saccade endpoint typically coincides roughly with the target, this protocol comprised the presentation of two nearby saccade targets, leading to a distinct spatial dissociation between target locations and saccade endpoint on a substantial number of trials. The paradigm allowed us to compare presaccadic visual discrimination performance at the endpoint of accurate saccades (landing at one of the saccade targets) and of averaging saccades (landing at an intermediate location in between the two targets). We observed a selective enhancement of visual sensitivity at the endpoint of accurate saccades but not at the endpoint of averaging saccades. Rather, before the execution of averaging saccades, visual sensitivity was equally enhanced at both targets, suggesting that saccade averaging follows from unresolved attentional selection among the saccade targets. These results argue against a mandatory coupling between visual attention and saccade programming based on a direct measure of presaccadic visual sensitivity rather than saccadic reaction times, which have been used in other protocols to draw similar conclusions. While our protocol provides a useful framework to investigate the relationship between visual attention and saccadic eye movements at the behavioral level, it can also be combined with electrophysiological measures to extend insights at the neuronal level.

This experimental protocol combined eye tracking and the assessment of presaccadic visual sensitivity in a dual task paradigm, consisting of a free choice saccade task and a visual discrimination task, to investigate the deployment of visual spatial attention before both, accurate and averaging saccades.

アイトラッ キングによる正確かつ平均サッカード前に視覚的注意の展開と視覚感度の評価を調査

This experimental protocol was designed to investigate whether visual attention is obligatorily deployed at the endpoint of saccades. To this end, we ...

Integrating Visual Psychophysical Assays within a Y-Maze to Isolate the Role that Visual Features Play in Navigational Decisions

Collective animal behavior arises from individual motivations and social interactions that are critical for individual fitness. Fish have long inspired investigations into collective motion, specifically, their ability to integrate environmental and social information across ecological contexts. This demonstration illustrates techniques used for quantifying behavioral responses of fish, in this case, Golden Shiner (Notemigonus crysoleucas), to visual stimuli using computer visualization and digital image analysis. Recent advancements in computer visualization allow for empirical testing in the lab where visual features can be controlled and finely manipulated to isolate the mechanisms of social interactions. The purpose of this method is to isolate visual features that can influence the directional decisions of the individual, whether solitary or with groups. This protocol provides specifics on the physical Y-maze domain, recording equipment, settings and calibrations of the projector and animation, experimental steps and data analyses. These techniques demonstrate that computer animation can elicit biologically-meaningful responses. Moreover, the techniques are easily adaptable to test alternative hypotheses, domains, and species for a broad range of experimental applications. The use of virtual stimuli allows for the reduction and replacement of the number of live animals required, and consequently reduces laboratory overhead.
This demonstration tests the hypothesis that small relative differences in the movement speeds (2 body lengths per second) of virtual conspecifics will improve the speed and accuracy with which shiners follow the directional cues provided by the virtual silhouettes. Results show that shiners directional decisions are significantly affected by increases in the speed of the visual cues, even in the presence of background noise (67% image coherency). In the absence of any motion cues, subjects chose their directions at random. The relationship between decision speed and cue speed was variable and increases in cue speed had a modestly disproportionate influence on directional accuracy.

Here, we present a protocol to demonstrate a behavioral assay that quantifies how alternative visual features, such as motion cues, influence directional decisions in fish. Representative data are presented on the speed and accuracy where Golden Shiner (Notemigonus crysoleucas) follow virtual fish movements.

Y-Maze内の視覚心理物理学アッセイを統合し、ナビゲーション上の意思決定で視覚的特徴が果たす役割を分離する

Collective animal behavior arises from individual motivations and social interactions that are critical for individual fitness. Fish have long inspired ...

Dynamic Digital Biomarkers of Motor and Cognitive Function in Parkinson's Disease

As Parkinson&#8217;s disease (PD) is a heterogeneous disorder, personalized medicine is truly required to optimize care. In their current form, standard scores from paper and pencil symptom- measures traditionally used to track disease progression are too coarse (discrete) to capture the granularity of the clinical phenomena under consideration, in the face of tremendous symptom diversity. For this reason, sensors, wearables, and mobile devices are increasingly incorporated into PD research and routine care. These digital measures, while more precise, yield data that are less standardized and interpretable than traditional measures, and consequently, the two types of data remain largely siloed. Both of these issues present barriers to the broad clinical application of the field&#8217;s most precise assessment tools. This protocol addresses both problems. Using traditional tasks to measure cognition and motor control, we test the participant, while co-registering biophysical signals unobtrusively using wearables. We then integrate the scores from traditional paper-and-pencil methods with the digital data that we continuously register. We offer a new standardized data type and unifying statistical platform that enables the dynamic tracking of change in the person&#8217;s stochastic signatures under different conditions that probe different functional levels of neuromotor control, ranging from voluntary to autonomic. The protocol and standardized statistical framework offer dynamic digital biomarkers of physical and cognitive function in PD that correspond to validated clinical scales, while significantly improving their precision.&#160;

This protocol offers a digitization of portions of traditional clinical tasks commonly used to measure cognition and motor control in Parkinson&#8217;s disease. Clinical tasks are digitized while biophysical rhythms are co-registered from different functional levels of the nervous systems, ranging from voluntary, spontaneous, automatic to autonomic.

パーキンソン病における運動と認知機能の動的デジタルバイオマーカー

As Parkinson&#8217;s disease (PD) is a heterogeneous disorder, personalized medicine is truly required to optimize care. In their current form, standard ...