撮影材料の彼女のヘルプありがとう玲子安藤。この研究は、挑戦的萌芽研究費補助金によって支えられた (日本学術振興会科研費助成番号 16 K 15196)。

<ol>
	<li>Bryan, K. J., Lee, H., Perry, G., Smith, M. A., Casadesus, G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> Transgenic Mouse Models of Alzheimer's Disease: Behavioral Testing and Considerations. Methods of Behavior Analysis in Neuroscience. , (2009).</li><li>Nestler, E. J., Hyman, S. E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Animal+models+of+neuropsychiatric+disorders.">Animal models of neuropsychiatric disorders.</a> Nature Neuroscience. 13 (10), 1161-1169 (2010).</li><li>Crawley, J. N. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Behavioral+Phenotyping+Strategies+for+Mutant+Mice.">Behavioral Phenotyping Strategies for Mutant Mice.</a> Neuron. 57 (6), 809-818 (2008).</li><li>Zarringhalam, K., Ka, 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=An+open+system+for+automatic+home-cage+behavioral+analysis+and+its+application+to+male+and+female+mouse+models+of+Huntington's+disease.">An open system for automatic home-cage behavioral analysis and its application to male and female mouse models of Huntington's disease.</a> Behavioural Brain Research. 229 (1), 216-225 (2012).</li><li>Prusiner, S. B., Jackson, W. S., King, O. 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K., Shum, D., Toulopoulou, T., Chen, E. Y. H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Assessment+of+executive+functions:+Review+of+instruments+and+identification+of+critical+issues.">Assessment of executive functions: Review of instruments and identification of critical issues.</a> Archives of Clinical Neuropsychology. 23 (2), 201-216 (2008).</li><li>Jurado, M. 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A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+5-Choice+Serial+Reaction+Time+Task:+A+Task+of+Attention+and+Impulse+Control+for+Rodents.">The 5-Choice Serial Reaction Time Task: A Task of Attention and Impulse Control for Rodents.</a> Journal of Visualized Experiments. (90), e51574 (2014).</li><li>Codita, A., Gumucio, 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=Impaired+behavior+of+female+tg-ArcSwe+APP+mice+in+the+IntelliCage:+A+longitudinal+study.">Impaired behavior of female tg-ArcSwe APP mice in the IntelliCage: A longitudinal study.</a> Behavioural brain research. 215 (1), 83-94 (2010).</li><li>Blumstein, D. T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Habituation+and+sensitization:+new+thoughts+about+old+ideas.">Habituation and sensitization: new thoughts about old ideas.</a> Animal Behaviour. 120, 255-262 (2016).</li><li>Endo, T., Maekawa, F., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Automated+test+of+behavioral+flexibility+in+mice+using+a+behavioral+sequencing+task+in+IntelliCage.">Automated test of behavioral flexibility in mice using a behavioral sequencing task in IntelliCage.</a> Behavioural brain research. 221 (1), 172-181 (2011).</li><li>Voikar, V., Colacicco, G., Gruber, O., Vannoni, E., Lipp, H. -. P., Wolfer, D. P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Conditioned+response+suppression+in+the+IntelliCage:+assessment+of+mouse+strain+differences+and+effects+of+hippocampal+and+striatal+lesions+on+acquisition+and+retention+of+memory.">Conditioned response suppression in the IntelliCage: assessment of mouse strain differences and effects of hippocampal and striatal lesions on acquisition and retention of memory.</a> Behavioural brain research. 213 (2), 304-312 (2010).</li><li>Pu&#347;cian, A., &#321;&#281;ski, S., G&#243;rkiewicz, T., Meyza, K., Lipp, H. -. P., Knapska, E. <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+automated+behavioral+test+battery+assessing+cognitive+rigidity+in+two+genetic+mouse+models+of+autism.">A novel automated behavioral test battery assessing cognitive rigidity in two genetic mouse models of autism.</a> Frontiers in Behavioral Neuroscience. 8, 140 (2014).</li><li>Voikar, V., Colacicco, G., Gruber, O., Vannoni, E., Lipp, H. -. P., Wolfer, D. P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Conditioned+response+suppression+in+the+IntelliCage:+assessment+of+mouse+strain+differences+and+effects+of+hippocampal+and+striatal+lesions+on+acquisition+and+retention+of+memory.">Conditioned response suppression in the IntelliCage: assessment of mouse strain differences and effects of hippocampal and striatal lesions on acquisition and retention of memory.</a> Behavioural brain research. 213 (2), 304-312 (2010).</li><li>Harda, Z., Dzik, J. 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=Autophosphorylation+of+&#945;CaMKII+affects+social+interactions+in+mice.">Autophosphorylation of &#945;CaMKII affects social interactions in mice.</a> Genes, Brain and Behavior. , e12457 (2018).</li><li>Aarts, E., Maroteaux, G., 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=The+light+spot+test:+Measuring+anxiety+in+mice+in+an+automated+home-cage+environment.">The light spot test: Measuring anxiety in mice in an automated home-cage environment.</a> Behavioural Brain Research. 294, 123-130 (2015).</li><li>Safi, K., Neuh&#228;usser-Wespy, F., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Mouse+anxiety+models+and+an+example+of+an+experimental+setup+using+unconditioned+avoidance+in+an+automated+system+-IntelliCage.">Mouse anxiety models and an example of an experimental setup using unconditioned avoidance in an automated system -IntelliCage.</a> Cognition Brain &amp; Behavior. 10 (4), 475-488 (2006).</li><li>Dzik, J. M., Pu&#347;cian, A., Mijakowska, Z., Radwanska, K., &#321;&#281;ski, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=PyMICE:+APython+library+for+analysis+of+IntelliCage+data.">PyMICE: APython library for analysis of IntelliCage data.</a> Behavior Research Methods. 50 (2), 804-815 (2018).</li></ol>

利害の対立が宣言されていません。

本稿では、遺伝子組み換えの広告モデルで長期的な認知・行動のアッセイの自動化されたホーム ケージ監視システムを使用してメソッドについて説明します。最も重要なステップは、適切な位置にトランスポンダーの注入です。移植を実行する前に、トランスポンダーの有効期限の日付が渡されないことを確認します。2 番目の重要な点は、マイナーな問題は、調査の間により深刻な 1 つをなることができるその後、特に毎日、システムの機能を確認する (すなわち、ドア、落ちてアウト トランスポンダー、悪い電気接続などを積み上げ。.).第三に、実験スケジュールの中で多くの問題がありますので、トラブル シュートすることができることが不可欠です。
本稿は、認知評価タスクの基本的なパッケージを導入しました。これらのタスクは、従来の行動テストを参照して作り出されたが、彼らは完全に従来の検査を模倣できません。たとえば、SRT のタスクは、選択モードを設定しません。5 選択シリアル選択課題 (5CSRTT)、SRT タスクのモデル通常 9、5 または 3 穴精度16,17を測定する nosepoke の商工会議所で行われています。私たちのチームは以前、SRT の選択バージョンを実装しようが、マウスに比較的長い時間 (2 週間以上) 内の規則の習得に失敗しました。このシステムのユーザーの違いは、留意し、データを慎重に話し合います。
別の問題は、繰り返し測定の限界についてです。以前の研究18で述べたように、最初の 1 つは、繰り返し実験が年齢の影響を単純に比較できないです。PA テストの 2 番目のデータが広告モデル10で記憶障害をレプリケートに失敗したことがわかった。すべての遺伝子型のパフォーマンスは、最初の PA テストよりもはるかに悪化だった。この違いは、嫌悪刺激 (前の PA 作業の体験) 年齢差、慣れから来るかもしれない。実験者は、繰り返しの効果を気に、タスクの順序を検討してください。2 番目の PA テストの aversive 刺激の慣れを克服するために強力な空気パフ刺激を使用するまたは異なるタイプの寝具などいくつかの新奇環境刺激を追加するより良いであろう19の音ですか。
様々 な研究を進めている新しい方法およびプロトコル自動ホーム ケージ監視研究20,21,22,23,24,25、 26, とオープン ソース ライブラリ27を使用してサポートするソフトウェア。したがって、システムの可能性を広げています。最後に、システムは、自動化されたハイスループット行動表現型解析と疾患モデルの検証に有益な認知機能の広い範囲の研究に使用する長期的な試金検診を提供します。

過去 10 年間以上神経疾患モデル動物の開発は、その根拠と治療の進歩1,2,3を促進するために機構についての理解を提供しています。遺伝的動物モデルで高スループットの行動テスト バッテリーのアプリケーションは、人間の病気のメカニズムと薬物療法の識別を検討する研究ツールです。研究テスト バッテリー適合高齢者の長期観察のためおよび/または認知症モデルに専門人材と時間の偉大な量を消費する所あります伝統的。ホーム ケージ監視システムは、人間が行動観察のコストを減らすだろうとコスト効果の高い戦略になります。いくつかの研究チームは、ホーム ケージ4,5,6の単一の個々 の行動表現型解析を支援するビジョン ベースの自動化ツールを開発しました。ただし、このようなメソッドは、社会的相互作用、テスト環境のサイズおよびさまざまな認知機能を含む行動対策を制限します。IntelliCage は、ソーシャル ホーム ケージで様々 な認知タスクを実行するように設計第二世代ホーム ケージ監視システムです。重要なは、このメソッドは、毎日できる認知機能の評価と長期行動監視を実行する私たちの処理をなくすことができ、それ専門の実用的な処理のための要件を排除でき、再現性の高いを有効にします。データ集録7。ここでは、長期的に述べる表現型解析と検証されているアルツハイマー病 (AD) の遺伝的マウスモデルで最近自動ホーム ケージの監視機能を使用して8,9,10に生成されます。システム。空間的な学習機能と執行機能の評価を含んだテスト バッテリーを複数の年齢ポイント (9-12、14-17 ヶ月) で繰り返し行った。この年齢依存した表現では、さまざまな認知的側面に関する遺伝子の一時的/恒久的なエフェクトを識別することができました。いくつかの広告のモデルが自動ホーム ケージ システム監視10を使用して長期的な分析でテストいくつかの認知的側面の非定常かつ恒久的な表現型を示したことが分かった。したがって、ホーム ケージ監視システムを使用して自動化された研究は有益であり、長期的な行動表現型解析と高次脳機能障害の様々 なモデルでの検証のため費用対効果。

<table>
	<tbody>
		<tr>
			<td>IntelliCage</td>
			<td>TSE Systems</td>
			<td>-</td>
			<td>Parchased in 2011 or later</td>
		</tr>
		<tr>
			<td>PC</td>
			<td>Dell</td>
			<td>Inspiron 580s</td>
			<td>-</td>
		</tr>
		<tr>
			<td>Display</td>
			<td>Dell</td>
			<td>SI75T-WL</td>
			<td>-</td>
		</tr>
		<tr>
			<td>ALPHA-dri</td>
			<td>Shepherd Specialty Papers</td>
			<td>-</td>
			<td>Standard bedding</td>
		</tr>
		<tr>
			<td>Aron Alpha (Krasy Glue) 2g</td>
			<td>Toagosei (Krasy Glue)</td>
			<td>#04612</td>
			<td>Cyanoacrylates for gluing magnet and blak arm</td>
		</tr>
		<tr>
			<td>Handheld Transponder Reader</td>
			<td>BTS-ID</td>
			<td>R-560</td>
			<td>Transponder reader, which reads both Trovan and DataMars</td>
		</tr>
		<tr>
			<td>Transponder</td>
			<td>DataMars</td>
			<td>T-VA, T-VAS, or another series</td>
			<td>Basic package of transponders and implanters</td>
		</tr>
		<tr>
			<td>Diamond Grip Plus</td>
			<td>Ansel Microflex</td>
			<td>DGP-INT-M</td>
			<td>Experimental glove</td>
		</tr>
		<tr>
			<td>Isoflurane</td>
			<td>Pfizer</td>
			<td>1119701G1092</td>
			<td>-</td>
		</tr>
		<tr>
			<td>Vaporizer for small animals</td>
			<td>DS Pharma Biomedical</td>
			<td>SF-B01</td>
			<td>Facemask included</td>
		</tr>
		<tr>
			<td>Neo-Medrol</td>
			<td>Pfizer</td>
			<td>006472-001</td>
			<td>Eye ointment</td>
		</tr>
		<tr>
			<td>Ethanol (70%)</td>
			<td>-</td>
			<td>-</td>
			<td>-</td>
		</tr>
		<tr>
			<td>Excel</td>
			<td>Microsoft</td>
			<td>00202-51382-15524-AA928</td>
			<td>For data analysis</td>
		</tr>
	</tbody>
</table>

automated, long-term behavioral assay for cognitive functions in multiple genetic models of alzheimer's disease, using intellicage

複数の要因-加齢や遺伝子など、認知機能の低下に頻繁に関連付けられています。アルツハイマー病 (AD) などの認知機能低下の遺伝子組み換えマウス モデル根本的なメカニズムの解明し、治療の進歩を促進するために有望なツールとなっています。広告は、認知機能の低下の場合、モデルで予想される行動異常の解析検証に重要なステップです。研究者から需要の実質的な努力を高齢化の影響を検討する実験動物の長期行動調査。IntelliCage システムは、毎日の人間の処理の必要性を排除するマウス用高スループットとコスト効果の高いテスト電池です。ここで述べる遺伝的アルツハイマー病モデルの長期的な表現でのシステムの利用方法具体的な認知機能に焦点を当てします。実験では、空間的な学習機能と執行機能を評価するテストの繰り返しバッテリを採用しています。この費用対効果の年齢依存した表現型解析はさまざまな認知的側面に関する遺伝子の一時的/恒久的な影響を確認することができます。

以前の研究では、広告モデルの年齢依存性の認知障害は自動化されたホーム ケージ システム監視10を用いた実験により検出されました。PP の広告モデルの彼らのパフォーマンスは若年成人と高齢者; の両方でそのままだったただし、PPR のパフォーマンスだった大幅と徐々 に障害 (図 6)。また、そのような特徴は15認知に影響を与えるので適応段階で全般的な動作や不安を観察することが重要です。広告モデルは総異常を FA、NP と DSA のセッションで訪問、nosepoke、舐めている数字で表示されませんでした。したがって、広告モデルは、柔軟性が低いかもしれません。
遂行機能を評価するには、SRT と DD で行動のパフォーマンスを記録しました。古い広告モデル (NL-G-F) は、SRT (SRT テスト 2) (図 8) の最後の段階で精度を欠いていた。簡易 compulsivity 若い大人および NL G F マウスの旧科目で観察された (図 9 bトップ)。興味深いことに、古い時代の若い大人をした NL F マウスの compulsivity の増加があった、それなった野生型マウス (図 9 b下) に匹敵します。これは NL F 突然変異の一時的な表現型の例です。
<img alt="Figure 1" class="xfigimg" src="/files/ftp_upload/58009/58009fig1.jpg"> 図 1: ホーム ケージ モニタリング システムのコンポーネント。(A) システムの概要。(B) コネクタの位置。(C) コーナーはオペラント ドアの商工会議所します。<a href="https://www-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/58009/58009fig1large.jpg" target="_blank">この図の拡大版を表示するのにはここをクリックしてください</a>。
<img alt="Figure 2" class="xfigimg" src="/files/ftp_upload/58009/58009fig2.jpg"> 図 2: 研究のための集合住宅の例です。通常、ケージごと 12 マウスが使用されます。4 つのグループ (1 つの野生型と 3 つ遺伝モデル) を使用して、場合 IntelliCage ごとグループごとの 3 つのマウスが適切と見なされます。<a href="https://www-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/58009/58009fig2large.jpg" target="_blank">この図の拡大版を表示するのにはここをクリックしてください</a>。
<img alt="Figure 3" class="xfigimg" src="/files/ftp_upload/58009/58009fig3.jpg"> 図 3: システムのためのソフトウェア。(A)「デザイナー」を実験ファイルのビルドに使用します。左: 動物のリスト部分には、動物およびグループの定義の情報が含まれています。右: モジュール領域は、実験的操作を定義する使用されます。(B)「コント ローラー」は、実行、モニター、およびレコードの実験に使用できます。左: nosepoke、動物の訪問を表示する 4 つのコーナーで舐めているとケージの 1 つの状態です。右: いくつかのトラブルが発生した場合、アラーム ウィンドウが表示されます。(C) アナライザーは、処理およびコント ローラーによって取得したデータをエクスポートする使用できます。左: すべてのデータは、動物、環境、ケージと時間の情報がタグ付けされます。フィルターさらに Excel または他の分析ソフトウェアで分析に役立つでしょう。右: のタイムライン (また nosepoke かなめ) の訪問が個別に表示することができます。<a href="https://www-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/58009/58009fig3large.jpg" target="_blank">この図の拡大版を表示するのにはここをクリックしてください</a>。
<img alt="Figure 4" class="xfigimg" src="/files/ftp_upload/58009/58009fig4.jpg"> 図 4: トランスポンダー注入。トランスポンダー (DataMars) の (A) マイクロ チップ。(B) 側は、トランスポンダー注入 (transpondering) の表示します。脊髄に原因の損傷を避けるため。(C) トランスポンダーの平面図です。<a href="https://www-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/58009/58009fig4large.jpg" target="_blank">この図の拡大版を表示するのにはここをクリックしてください</a>。
<img alt="Figure 5" class="xfigimg" src="/files/ftp_upload/58009/58009fig5.jpg"> 図 5: 自動化されたホーム ケージ監視システム認知評価のための実験の時間線。認知的評価のためのテスト バッテリーを 2 回施行した (第 1 セット、9-12 ヶ月; 第 2 セット、14-17 ヶ月) 最後の活動を評価するための実験が続く (3 セット [18 ヶ])。このバッテリーは複数の認知ドメインを評価するために指定された (色によって示される-レッド: 一般的な活動;青: 空間的な学習および記憶;緑: エグゼクティブ関数)、検証と予想される認知障害の特性解析の利点を持っています。FA: 無料適応;警察庁: Nosepoke 適応;DSA: 飲んでセッション適応;PP: 場所選好;PPR: 場所選好逆転;SRT: 系列反応時間 (衝動性、注意の);PA: 場所の回避;DD: 遅延割引。<a href="https://www-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/58009/58009fig5large.jpg" target="_blank">この図の拡大版を表示するのにはここをクリックしてください</a>。
<img alt="Figure 6" class="xfigimg" src="/files/ftp_upload/58009/58009fig6.jpg"> 図 6: 実験的なデザインと PP と PPR のタスクの代表の結果。(A) 上部、PP または PPR の例モジュール設計。下、正しいコーナーの設定 PPR の反対側に変更します。年齢で誘発される広告モデル (NL-G-F) の学習空間の反転 (B) 赤字。データは、平均値 (SEM) の平均 ± 標準誤差として表されます。∗p < 0.05;∗∗p < 0.01。色を示す比較のグループ: 青: NL 対重量;赤: NL F 対重量;緑: NL G F 対 WT。この図は、参照10から変更されています。<a href="https://www-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/58009/58009fig6large.jpg" target="_blank">この図の拡大版を表示するのにはここをクリックしてください</a>。
<img alt="Figure 7" class="xfigimg" src="/files/ftp_upload/58009/58009fig7.jpg"> 図 7: SRT タスクの試験フローします。左: SRT (imp) のトライアルの流れ。最初の nosepoke が正しい側を定義し、遅延期間を開始する (0.5 – 4.0 s)、黄色の Led がオンにした後。その扉を開きます。右: SRT (att) のトライアルの流れ。最初の nosepoke が正しい側を定義し、遅延期間を開始 (2.0 s) 後に、短い時間で黄色の Led がオンになっている (0.2 – 1.0 s)。マウスは、nosepokes を許可する期間を提供して (限られた保持、2 s)。ドアが開いて (5 s) 限られた保留中最初の nosepoke 正しい nosepoke した後にのみです。<a href="https://www-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/58009/58009fig7large.jpg" target="_blank">この図の拡大版を表示するのにはここをクリックしてください</a>。
<img alt="Figure 8" class="xfigimg" src="/files/ftp_upload/58009/58009fig8.jpg"> 図 8: 実験的なデザインと SRT タスクの代表の結果。(A) SRT の例モジュール設計。(B) 注意の年齢でに固有の広告モデルで減少します。データは、平均 ± SEM. ∗pとして表現される < 0.05;∗∗p < 0.01。色を示す比較のグループ: 青: NL 対重量;赤: NL F 対重量;緑: NL G F 対 WT。この図は、参照10から変更されています。<a href="https://www-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/58009/58009fig8large.jpg" target="_blank">この図の拡大版を表示するのにはここをクリックしてください</a>。
<img alt="Figure 9" class="xfigimg" src="/files/ftp_upload/58009/58009fig9.jpg"> 図 9: 実験的なデザインと DD タスクの代表の結果。(A) DD タスク モジュールの例。(B) 若年・高年齢で広告モデル (NL-G-F) の compulsivity の促進します。これは、表現型の例です。その一方で、compulsivity は、別の広告モデル (NL-F) 一過性増資。データは、平均 ± SEM. ∗pとして表現される < 0.05;∗∗p < 0.01。色を示す比較のグループ: 青: NL 対重量;赤: NL F 対重量;緑: NL G F 対 WT。この図は、前の仕事の10から変更されています。<a href="https://www-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/58009/58009fig9large.jpg" target="_blank">この図の拡大版を表示するのにはここをクリックしてください</a>。

Watch this Scientific Journal Video about Automated, Long-term Behavioral Assay for Cognitive Functions in Multiple Genetic Models of Alzheimer's Disease, Using IntelliCage at JoVE.com

Automated, Long-term Behavioral Assay for Cognitive Functions in Multiple Genetic Models of Alzheimer's Disease, Using IntelliCage

本稿では、オペラント条件づけと自動化されたハイスループットの行動監視システム IntelliCage システムを使用して、アルツハイマー病の遺伝的モデルの認知評価のためのプロトコルについて説明します。

アルツハイマー病、IntelliCage を使用しての複数の遺伝モデルにおける認知機能の長期的な行動のアッセイの自動化

Multiple factors&#8212;such as aging and genes&#8212;are frequently associated with cognitive decline. Genetically modified mouse models of cognitive ...

automated-long-term-behavioral-assay-for-cognitive-functions-multiple

Nanyang Technological University

Research

JoVE Journal

Behavior

12.0K ビュー.  RIKEN. 本稿では、オペラント条件づけと自動化されたハイスループットの行動監視システム IntelliCage システムを使用して、アルツハイマー病の遺伝的モデルの認知評価のためのプロトコルについて説明します。

ビデオ: Automated, Long-term Behavioral Assay for Cognitive Functions in Multiple Genetic Models of Alzheimer's Disease, Using IntelliCage

Assessment of Age-related Changes in Cognitive Functions Using EmoCogMeter, a Novel Tablet-computer Based Approach

The main goal of this study was to assess the usability of a tablet-computer-based application (EmoCogMeter) in investigating the effects of age on cognitive functions across the lifespan in a sample of 378 healthy subjects (age range 18-89 years). Consistent with previous findings we found an age-related cognitive decline across a wide range of neuropsychological domains (memory, attention, executive functions), thereby proving the usability of our tablet-based application. Regardless of prior computer experience, subjects of all age groups were able to perform the tasks without instruction or feedback from an experimenter. Increased motivation and compliance proved to be beneficial for task performance, thereby potentially increasing the validity of the results. Our promising findings underline the great clinical and practical potential of a tablet-based application for detection and monitoring of cognitive dysfunction.

We tested the usability of a tablet-computer-based application (EmoCogMeter) in investigating the effects of age on cognition. Results show an age-related cognitive decline, thereby proving the usability of our application. Findings underline the great clinical and practical potential of a tablet-based application for detection and monitoring of cognitive dysfunction.

EmoCogMeter、新規タブレットコンピュータベースのアプローチを用いて認知機能の加齢変化の評価

The main goal of this study was to assess the usability of a tablet-computer-based application (EmoCogMeter) in investigating the effects of age on ...

行動学

Nest Building as an Indicator of Health and Welfare in Laboratory Mice

The minimization and alleviation of suffering has moral and scientific implications. In order to mitigate this negative experience one must be able to identify when an animal is actually in distress. Pain, illness, or distress cannot be managed if unrecognized. Evaluation of pain or illness typically involves the measurement of physiologic and behavioral indicators which are either invasive or not suitable for large scale assessment. The observation of nesting behavior shows promise as the basis of a species appropriate cage-side assessment tool for recognizing distress in mice. Here we demonstrate the utility of nest building behavior in laboratory mice as an ethologically relevant indicator of welfare. The methods presented can be successfully used to identify thermal stressors, aggressive cages, sickness, and pain. Observation of nest building behavior in mouse colonies provides a refinement to health and well-being assessment on a day to day basis.

We demonstrate the utility of nest building behavior in laboratory mice as an indicator of welfare. Nest scoring is a sensitive technique that is altered by temperature, illness, and aggression. The time to integrate into nest test (TINT) is a simple cage-side assessment that can detect postoperative pain.

The minimization and alleviation of  suffering has moral and scientific implications. In order to mitigate this  negative experience one must be able to ...

Automated, Quantitative Cognitive/Behavioral Screening of Mice: For Genetics, Pharmacology, Animal Cognition and Undergraduate Instruction

We describe a high-throughput, high-volume, fully automated, live-in 24/7 behavioral testing system for assessing the effects of genetic and pharmacological manipulations on basic mechanisms of cognition and learning in mice. A standard polypropylene mouse housing tub is connected through an acrylic tube to a standard commercial mouse test box. The test box has 3 hoppers, 2 of which are connected to pellet feeders. All are internally illuminable with an LED and monitored for head entries by infrared (IR) beams. Mice live in the environment, which eliminates handling during screening. They obtain their food during two or more daily feeding periods by performing in operant (instrumental) and Pavlovian (classical) protocols, for which we have written protocol-control software and quasi-real-time data analysis and graphing software. The data analysis and graphing routines are written in a MATLAB-based language created to simplify greatly the analysis of large time-stamped behavioral and physiological event records and to preserve a full data trail from raw data through all intermediate analyses to the published graphs and statistics within a single data structure. The data-analysis code harvests the data several times a day and subjects it to statistical and graphical analyses, which are automatically stored in the &#34;cloud&#34; and on in-lab computers. Thus, the progress of individual mice is visualized and quantified daily. The data-analysis code talks to the protocol-control code, permitting the automated advance from protocol to protocol of individual subjects. The behavioral protocols implemented are matching, autoshaping, timed hopper-switching, risk assessment in timed hopper-switching, impulsivity measurement, and the circadian anticipation of food availability. Open-source protocol-control and data-analysis code makes the addition of new protocols simple. Eight test environments fit in a 48 in x 24 in x 78 in&#160;cabinet; two such cabinets (16 environments) may be controlled by one computer.

Fully automated system for measuring physiologically meaningful properties of the mechanisms mediating spatial localization, temporal localization, duration, rate&#160;and probability estimation, risk assessment, impulsivity, and the accuracy and precision of memory, in order to assess the effects of genetic and pharmacological manipulations on foundational mechanisms of cognition in mice.

マウスの自動化、定量的認知/行動スクリーニング：遺伝学、薬理学、動物認知と学部命令について

We describe a high-throughput, high-volume, fully automated, live-in 24/7 behavioral testing system for assessing the effects of genetic and ...

Automated Visual Cognitive Tasks for Recording Neural Activity Using a Floor Projection Maze

Neuropsychological tasks used in primates to investigate mechanisms of learning and memory are typically visually guided cognitive tasks. We have developed visual cognitive tasks for rats using the Floor Projection Maze1,2&#160;that are optimized for visual abilities of rats permitting stronger comparisons of experimental findings with other species.
In order to investigate neural correlates of learning and memory, we have integrated electrophysiological recordings into fully automated cognitive tasks on the Floor Projection Maze1,2. Behavioral software interfaced with an animal tracking system allows monitoring of the animal's behavior with precise control of image presentation and reward contingencies for better trained animals. Integration with an in vivo electrophysiological recording system enables examination of behavioral correlates of neural activity at selected epochs of a given cognitive task.
We describe protocols for a model system that combines automated visual presentation of information to rodents and intracranial reward with electrophysiological approaches. Our model system offers a sophisticated set of tools as a framework for other cognitive tasks to better isolate and identify specific mechanisms contributing to particular cognitive processes.

We describe protocols for training rats for chronic electrophysiological recordings in fully automated cognitive tasks on a Floor Projection Maze.

フロアプロジェクション迷路を用いた記録神経活動のための自動化された視覚認知課題

Neuropsychological tasks used in primates to investigate mechanisms of learning and memory are typically visually guided cognitive tasks. We have ...

Behavioral Phenotyping of Murine Disease Models with the Integrated Behavioral Station (INBEST)

Due to rapid advances in genetic engineering, small rodents have become the preferred subjects in many disciplines of biomedical research. In studies of chronic CNS disorders, there is an increasing demand for murine models with high validity at the behavioral level. However, multiple pathogenic mechanisms and complex functional deficits often impose challenges to reliably measure and interpret behavior of chronically sick mice. Therefore, the assessment of peripheral pathology and a behavioral profile at several time points using a battery of tests are required. Video-tracking, behavioral spectroscopy, and remote acquisition of physiological measures are emerging technologies that allow for comprehensive, accurate, and unbiased behavioral analysis in a home-base-like setting. This report describes a refined phenotyping protocol, which includes a custom-made monitoring apparatus (Integrated Behavioral Station, INBEST) that focuses on prolonged measurements of basic functional outputs, such as spontaneous activity, food/water intake and motivated behavior in a relatively stress-free environment. Technical and conceptual improvements in INBEST design may further promote reproducibility and standardization of behavioral studies.

Behavioral Phenotyping of Murine Disease Models with the Integrated Behavioral Station INBEST

Prolonged and comprehensive monitoring of mice in a home-cage environment provides a deeper understanding of aberrant behavior in murine models of brain diseases. This paper describes the Integrated Behavioral Station (INBEST) as the key component of contemporary behavioral analysis.

統合された行動ステーション（INBEST）を有するマウス疾患モデルの行動表現型

Due to rapid advances in genetic engineering, small rodents have become the preferred subjects in many disciplines of biomedical research. In studies of ...

Behavioral and Locomotor Measurements Using an Open Field Activity Monitoring System for Skeletal Muscle Diseases

The open field activity monitoring system comprehensively assesses locomotor and behavioral activity levels of mice. It is a useful tool for assessing locomotive impairment in animal models of neuromuscular disease and efficacy of therapeutic drugs that may improve locomotion and/or muscle function. The open field activity measurement provides a different measure than muscle strength, which is commonly assessed by grip strength measurements. It can also show how drugs may affect other body systems as well when used with additional outcome measures. In addition, measures such as total distance traveled mirror the 6 min walk test, a clinical trial outcome measure. However, open field activity monitoring is also associated with significant challenges: Open field activity measurements vary according to animal strain, age, sex, and circadian rhythm. In addition, room temperature, humidity, lighting, noise, and even odor can affect assessment outcomes. Overall, this manuscript provides a well-tested and standardized open field activity SOP for preclinical trials in animal models of neuromuscular diseases. We provide a discussion of important considerations, typical results, data analysis, and detail the strengths and weaknesses of open field testing. In addition, we provide recommendations for optimal study design when using open field activity in a preclinical trial.

Open field activity levels are used to assess locomotive and behavioral activity levels. This protocol provides a well-designed, standardized protocol to use in preclinical trials for neuromuscular disorders.

骨格筋の病気のためにオープンフィールドアクティビティ·モニタリングシステムを用いた行動と自発運動の測定

The open field activity monitoring system comprehensively assesses locomotor and behavioral activity levels of mice. It is a useful tool for assessing ...

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 ...

Assessment of Social Cognition in Non-human Primates Using a Network of Computerized Automated Learning Device (ALDM) Test Systems

Fagot &#38; Paleressompoulle1 and Fagot &#38; Bonte2 have published an automated learning device (ALDM) for the study of cognitive abilities of monkeys maintained in semi-free ranging conditions. Data accumulated during the last five years have consistently demonstrated the efficiency of this protocol to investigate individual/physical cognition in monkeys, and have further shown that this procedure reduces stress level during animal testing3. This paper demonstrates that networks of ALDM can also be used to investigate different facets of social cognition and in-group expressed behaviors in monkeys, and describes three illustrative protocols developed for that purpose. The first study demonstrates how ethological assessments of social behavior and computerized assessments of cognitive performance could be integrated to investigate the effects of socially exhibited moods on the cognitive performance of individuals. The second study shows that batteries of ALDM running in parallel can provide unique information on the influence of the presence of others on task performance. Finally, the last study shows that networks of ALDM test units can also be used to study issues related to social transmission and cultural evolution. Combined together, these three studies demonstrate clearly that ALDM testing is a highly promising experimental tool for bridging the gap in the animal literature between research on individual cognition and research on social cognition.

Assessment of Social Cognition in Non-human Primates Using a Network of Computerized Automated Learning Device ALDM Test Systems

Fagot &#38; Paleressompoulle1 have published an automated learning device (ALDM) aimed at testing individual cognitive abilities in semi-free ranging monkeys. The main goal of our protocol is to use a network of ALDM test units to study social cognition in non-human primates.

コンピューターの自動学習装置（ALDM）テストシステムのネットワークを用いた非ヒト霊長類における社会的認知の評価

Fagot &#38; Paleressompoulle1 and Fagot &#38; Bonte2 have published an automated learning device (ALDM) for the study of cognitive abilities of monkeys ...

The 4 Mountains Test: A Short Test of Spatial Memory with High Sensitivity for the Diagnosis of Pre-dementia Alzheimer's Disease

This protocol describes the administration of the 4 Mountains Test (4MT), a short test of spatial memory, in which memory for the topographical layout of four mountains within a computer-generated landscape is tested using a delayed match-to-sample paradigm. Allocentric spatial memory is assessed by altering the viewpoint, colors and textures between the initially presented and target images.
Allocentric spatial memory is a key function of the hippocampus, one of the earliest brain regions to be affected in Alzheimer&#39;s disease (AD) and impairment of hippocampal function predates the onset of dementia. It was hypothesized that performance on the 4MT would aid the diagnosis of predementia AD, which manifests clinically as Mild Cognitive Impairment (MCI).
The 4MT was applied to patients with MCI, stratified further based on cerebrospinal fluid (CSF) AD biomarker status (10 MCI biomarker positive, 9 MCI biomarker negative), and with mild AD dementia, as well as healthy controls. Comparator tests included tests of episodic memory and attention widely accepted as sensitive measures of early AD. Behavioral data were correlated with quantitative MRI measures of the hippocampus, precuneus and posterior cingulate gyrus.
4MT scores were significantly different between the two MCI groups (p = 0.001), with a test score of &#8804;8/15 associated with 100% sensitivity and 78% specificity for the classification of MCI with positive AD biomarkers, i.e., predementia AD. 4MT test scores correlated with hippocampal volume (r = 0.42) and cortical thickness of the precuneus (r = 0.55).
In conclusion, the 4MT is effective in identifying the early stages of AD. The short duration, easy application and scoring, and favorable psychometric properties of the 4MT fulfil the need for a simple but accurate diagnostic test for predementia AD.

This article describes the 4 Mountains Test (4MT), a hippocampus-dependent test of working allocentric spatial memory. The hippocampus is affected early in Alzheimer's disease (AD) and this article outlines the 4MT methodology and results of patient testing, which demonstrates the value of the 4MT in the diagnosis of pre-dementia AD.

4山脈テスト：プレ認知症、アルツハイマー病の診断のための高感度と空間記憶のショートテスト

This protocol describes the administration of the 4 Mountains Test (4MT), a short test of spatial memory, in which memory for the topographical layout of ...

Using the Race Model Inequality to Quantify Behavioral Multisensory Integration Effects

Multisensory integration research investigates how the brain processes simultaneous sensory information. Research on animals (mainly cats and primates) and humans reveal that intact multisensory integration is crucial for functioning in the real world, including both cognitive and physical activities. Much of the research conducted over the past several decades documents multisensory integration effects using diverse psychophysical, electrophysiological, and neuroimaging techniques. While its presence has been reported, the methods used to determine the magnitude of multisensory integration effects varies and typically faces much criticism. In what follows, limitations of previous behavioral studies are outlined and a step-by-step tutorial for calculating the magnitude of multisensory integration effects using robust probability models is provided.

The current study aims to provide a step-by-step tutorial for calculating the magnitude of multisensory integration effects in an effort to facilitate the production of translational research studies across diverse clinical populations.

人種モデルの不等式を使用して行動多感覚統合効果を定量化する

Multisensory integration research investigates how the brain processes simultaneous sensory information. Research on animals (mainly cats and primates) ...