彼女の細心の編集のための手術準備科目、エリザベス ・ サムナーをイアン ・太字を感謝いたします。これらの研究は、橋渡しの外傷性脳損傷研究のための不機嫌なプロジェクトによって資金を供給チームの一員として完成しました。

<ol>
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L., Capra, B., Eidson, K., Garcia, J., Kennedy, D., Uchida, T., 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=Dose-dependent+neuronal+injury+after+traumatic+brain+injury.">Dose-dependent neuronal injury after traumatic brain injury.</a> Brain Research. 1044, 144-154 (2005).</li><li>Bramlett, H. M., Detrich, W. D. <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+consequences+of+Traumatic+Brain+Injury:+Current+Status+of+Potential+Mechanisms+of+Injury+and+Neurological+Outcomes.">Long-Term consequences of Traumatic Brain Injury: Current Status of Potential Mechanisms of Injury and Neurological Outcomes.</a> J. Neurotrauma. 32, 1-15 (2015).</li><li>Pierce, J. E. S., Smith, D. H., Trojanowski, J. Q., McIntosh, T. 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J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Allocentric+spatial+learning+by+hippocampectomised+rats:+A+further+test+of+the+"Spatial+Mapping"+and+"Working+Memory"+Theories+of+hippocampal+function.">Allocentric spatial learning by hippocampectomised rats: A further test of the "Spatial Mapping" and "Working Memory" Theories of hippocampal function.</a> The Quart J of Exp Psych. 38 (4), 365-395 (1986).</li><li>Dixon, C. E., Lyeth, B. G., Povlishock, J. T., Findling, R. L., Hamm, R. J., Marmarou, A., Young, H. F., Hayes, R. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+fluid-percussion+model+of+experimental+brain+injury+in+the+rat.">A fluid-percussion model of experimental brain injury in the rat.</a> J. Neurosurg. 67, 110-119 (1987).</li><li>DeWitt, D. S., Smith, T. G., Deyo, D. J., Miller, K. R., Uchida, T., Prough, D. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=L-arginine+and+superoxide+dismutase+prevent+or+reverse+cerebral+hypoperfusion+after+fluid-percussion+traumatic+brain+injury.">L-arginine and superoxide dismutase prevent or reverse cerebral hypoperfusion after fluid-percussion traumatic brain injury.</a> J. Neurotrauma. 14, 223-233 (1997).</li><li>R Core Team. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> R: A Language and Environment for Statistical Computing. , (2017).</li><li>Pohlert, 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> The Pairwise Multiple comparison of Mean Ranks Package (PMCMR) R package. , (2014).</li><li>Verma, P., Hellemans, K. G., Choi, F. Y., Yu, W., Weinberg, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Circadian+phase+and+sex+effects+on+depressive/anxiety-like+behaviors+and+HPA+axis+responses+to+acute+stress.">Circadian phase and sex effects on depressive/anxiety-like behaviors and HPA axis responses to acute stress.</a> Physiol Behav. 99, 276-285 (2010).</li><li>Schallert, T., Woodlee, M. T., Fleming, 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=Experimental+Focal+Ischemic+Injury:+Behavior-Brain+Interactions+and+Issues+of+Animal+Handling+and+Housing.">Experimental Focal Ischemic Injury: Behavior-Brain Interactions and Issues of Animal Handling and Housing.</a> ILAR J. 44 (2), 130-143 (2003).</li><li>Ruis, J. F., Rietveld, W. J., Buys, J. P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Properties+of+parametric+photic+entrainment+of+circadian+rhythms+in+the+rat.">Properties of parametric photic entrainment of circadian rhythms in the rat.</a> Physiol Behav. 50, 1233-1239 (1991).</li><li>Ferguson, S. A., Maier, K. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+review+of+seasonal/circannual+effects+of+laboratory+rodent+behavior.">A review of seasonal/circannual effects of laboratory rodent behavior.</a> Physiol Behav. 119, 130-136 (2003).</li><li>Fujimoto, S. T., Longhi, L., Saatman, K. E., McIntosh, T. K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Motor+and+cognitive+function+evaluation+following+experimental+traumatic+brain+injury.">Motor and cognitive function evaluation following experimental traumatic brain injury.</a> Neurosci &amp; Biobehav Reviews. , (2004).</li><li>Gold, E. M., Su, D., Lopez-Velazquez, L., Haus, D. L., Perez, H., Lacuesta, G. A., Anderson, A. J., Cummings, B. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Functional+assessment+of+long-term+deficits+in+rodent+models+of+traumatic+brain+injury.">Functional assessment of long-term deficits in rodent models of traumatic brain injury.</a> Regen. Med. 8 (4), 483-516 (2013).</li></ol>

著者が明らかに何もありません。

行動テストの任意の種類を行うときは、一致する重要です。この詳細には、微々 たるものが、動物の応答に大きな影響を与える多くの考慮事項が含まれます。見逃すことのできない重要なステップは、どんな実験の前に彼らの家/ケージハウジング状況に動物の馴化です。この準備には、行動の結果18を変更することができます動物の生理学的ストレス反応の影響が軽減されます。同様に、それはすべての動物を同じ方法で処理されるあらゆる努力が不可欠です。この一貫性は、住宅に前述のとおり、順化も順化訓練やテスト前に部屋の間の輸送と含まれています。この概念を誇張することはできません。ずさんな動物の取り扱いは任意の行動テスト19に悲惨です。同様に、あらゆる努力をする必要があります日の同じ時に動物をテストする暗いまたは光のサイクルの間にあるかどうか。一貫したテストを行う限り、ここで説明するテスト、光や暗い段階でテスト可能です。概日周期のさまざまな段階で行っている検査は、行動の結果18,20を変更する示されています。さらに、動物と同様に、ハンドラーは結果の精度を最大化するためにストレス フリー、穏やかな状態でなければなりません。
Neuroscore、特に偽陽性とネガが多い。偽陽性は、動物は処理およびテストに完全に慣れていないときに通常発生します。観察された応答は再帰とストレスや恐怖のうち反応から引き締め筋肉によらないので、動物が完全にリラックスして必要があります。緊張したハンドラー動物にストレスを送信することで結果に影響することができます。したがって、きつすぎるまたは余りに緩い、ラットを保持することができます両方問題となります。また、ハンドラーは神経質な場合これはラットの反応を混同できます。また、経験の浅いオブザーバーがラットの応答を誤解すること危険があります。良い訓練と実践の多くは、成功と、Neuroscore の一貫性に不可欠です。
一般に、これらのテストの主な関心事の大きな違いと時々 治療群間差は、不足しています。動物は、別のハンドラー、騒音、時刻と、潜在的に、季節21別様に反応できる、のであらゆる努力はすべての可能な交絡因子を減らすために行わなければなりません。
ここに示すビーム バランスとビーム徒歩タスクの結果は、これらのテストは、vestibulomotor 機能の欠損を検出する損傷後早期は役を示しています。これらの赤字は通常時1,14を解決します。このモデルで、受傷後 6 ヶ月で、傷害による赤字が解決されています。6 月時点の結果を示すナイーブ、偽、または傷つけられたラットに差がないです。ただし、すべてのラットされているリラックス ホーム檻の中で 6 ヶ月間、加齢と体重が増えます。したがって、彼らは、6 ヶ月間手術後 (または素朴な場合と同等) 再テストまで、本質的に古いと脂肪となっております、したがってグループだけでなく、彼らは彼らのベースライン 0 日と比較して実行しないでくださいすべての結果します。
もう一つの重要な考慮事項は、使用の動作テストが正しいテストです。たとえば、ここに採用テストは、特定の脳領域の関数を表すと考えられます。1 つの例は前庭系、バランスのために重要であります。皮質、視床、皮質ニューロン、荷-線条体、数名、大脳基底核を含む大脳皮質などの感覚運動機能に関与する脳の領域は、すべて vestibulomotor 調整に関与しています。したがって、ビーム バランスやはり徒歩で赤字はこれらの分野で潜在的な障害を示します。さらに、前頭前野と海馬は、学習と記憶関数は作業メモリの水迷路でテストに関与しています。正しいテストを選択した場合にも採用されているテストの限界を念頭に保たれなければなりません。たとえば、ここで説明したテストのどれも気分、抑うつ、不安、攻撃性、意思決定、または衝動性など社会的な相互作用などで赤字に敏感。繰り返しますが、評価される行動と脳領域の適切なテストを選択することが不可欠です。
行動データの解釈、分析は、慎重に接近する必要があります。それはので、その性質上、微妙な効果の原油の測定は、神経赤字の対策として行動の結果を使用して個別にテストの種類ごとの電力解析を含めるに勧めします。さらに、別のテスト統計解析の種類が必要です。たとえば、説明する Neuroscore とビーム バランス テスト、順序尺度を使用して動作を獲得する訓練を受けた観察者の解釈に依存します。これらの種類のデータが連続しないと正規分布ではない、だからノンパラ メトリック統計を使用するクラスカル-ウォリス検定などのセクション 6.1、6.2 に示すよう。または、ビーム徒歩とワーキング メモリ水迷路テストが連続データを作成し、正規分布、だからパラメトリック統計などを使用できる、一方通行 ANOVA または繰り返される措置二元セクション 6.3、6.4 に示すよう。
ここで示した行動のタスク時間の試練に立っているし、特にと組み合わせればラット、FPI モデル行動実験脳損傷のための他の多くの方法が存在するが、再現可能な結果を与えます。Neuroscore は、装置の最低実行短い評価です。反射と強度の他のテストは利用できる、横 pulsion タスク無動テスト、傾斜面のテスト、握力 (藤本らを参照してくださいなどの神経学的な評価に組み込むことが22金ら23). のビーム バランスはり徒歩タスクの説明が傷害の後 vestibulomotor 赤字の対策です。Vestibulomotor の調整は、総歩行障害の他の措置 Rotarod、回転棒が含まれます、フィールド活動を開く総行動の 1 つのメジャーと見なすことができます。、泳ぐ能力は、水迷路の中に泳ぐ速度測定も総運動協調性22,23の示します。ワーキング メモリ水迷路課題によるテストのこのセットを完了する両方参照 (トライアル 1 によって示される) 記憶障害を検出し、作業記憶の障害 (トライアル 2 または体験版 1 と体験版 2 の違いによって示されます)。認知機能の他の措置 8 腕放射状迷路、バーンズ迷路、新規オブジェクト認識テスト、水迷路のさまざまなバリエーションがあります。これらのバリエーションは、元のモリス水迷路、ラシュリー III 迷路 (また見なさい藤本ら22金ら23). この一連のテストができることが実証損傷後早期と様々 な角度でアウト傷害1後 12 ヶ月。
異なる系統、セックス、ラットの年齢とここでデモンストレーションされるタスクを使用ことができますさらに、ただし、宿泊施設が異なるサイズおよびより大きいもろさの場合に行われる必要があります。たとえば、古い、重いラット ビーム バランス課題や高齢者、虚弱なラットの広いビームを必要があります、必要があります水の遊泳時間の短い期間の迷路のことがあります。したがって、これらのテストの柔軟性のための部屋と仮説とさまざまな状況に対応する新しいテストの開発の可能性があります。

紹介した方法は TBI のラット実験モデルによる特定の脳領域の機能的障害を検出するために設計されています。4 つの異なる動作テストが表示されます。まず、neuroscore と呼ばれる短いの神経学的評価はいずれかは専門機器しますが、不要な行為を必要とせず実行できます。このテストでは、反射の赤字を検出します。第二に、ビーム バランス テストは、バランスを取る能力の赤字を検出します。このタスクは、順序尺度に基づくラットをスコアにハンドラーが必要ですし、ハンドラーのいくつかのトレーニングが必要です。ビーム バランス テストは狭いビームを必要とする、前庭系の赤字に敏感。3 番目のテストは、vestibulomotor 調整を評価します。このテストはビーム徒歩タスクと呼ばれ、ラットのいくつかの事前の訓練が必要ですが、この手順は、前の 2 つよりもより客観的にビームを走査する待機時間は主観的な採点に依存しない客観的に測定。この違いは、安全なボックスに到達する狭いビームを走査する時間は測定されるためです。・ ビーム歩行テストは、ビーム バランスだけでなく、エスケープ ボックスより長いビームを必要です。このテストは、モーターの調整とバランスの赤字を測定し、こうして小脳や運動関連脳領域への損傷に敏感であります。モリス水迷路 (MWM WM) のワーキング メモリーのバージョンは、主に海馬機能と前頭前皮質または執行機能との統合をテストします。示されているモリス水迷路のバージョンを参照メモリ1に赤字を検出する使用もできます。
これらのメソッドは、文献での老舗の実績に基づいて選ばれました。それぞれは、研究の多くの年にラットの複数系統と異なる所から多くの手に有効されています。ただし、過去には、受傷後は傷害は、「慢性」の時点が考慮された後 2 週間までを測定します。したがって、齧歯動物の TBI の慢性的な影響の研究のための行動のテクニックを確立する TBI を検出する感度を評価するために必要なこれらのよく知られているメソッドは損傷後長い時点で赤字を誘発しました。今、TBI のいくつかの齧歯動物モデル、FPI モデルは最も広く使用されているの一つです、この研究に適用されます。21950 年代に発表されたこのモデルと、それ以来、1,000 以上の論文は、ラット3FPI を採用しています。このタイプの傷害の病理は私たち4と他の人がよく記載されている5,6,7。簡単に言えば、海馬で神経細胞傷害がフッ素玉が損傷、すなわち24-48 h; 後短時間で染色を用いた線量に依存する示されています。総萎縮しキャビテーションは、内包と皮質の菲薄化を含む傷害6、7の後の 1 年間に報告されています。
脳機能の最も意味のある表現は、実験的脳損傷後の行動結果の措置を使用して評価されます。ただし、行動の結果を使用する FPI 実験の大半対策を行います、比較的早く通常傷害の後の 14 日に 1 から。メソッドを使用していくつかの行動の赤字は、傷害1後 12 ヶ月を検出できる、ここで示します。神経学的な機能、総 vestibulomotor 機能、細かい運動の調整後負傷日 (Pid) 1-3 と 3、6、12 ヶ月短い神経学的評価を用いた手術後に評価された (Neuroscore; シャラート8から変更)、ビーム バランス タスク、およびビーム徒歩タスク9,10,11。参照記憶および作業記憶は、モリス水迷路1,12,13のワーキング メモリーのバージョンを使用して評価されました。

<table>
	<tbody>
		<tr>
			<td>Sprague-Dawley rats</td>
			<td>Charles Rivers Laboratories 
			251 Ballardvale St 
			Wilmington, MA 01887-1096 
			Phone: 800-522-7287</td>
			<td>CD-IGS rats, strain code 001</td>
			<td>male, albino, 300-350g at arrival</td>
		</tr>
		<tr>
			<td>Name</td>
			<td>Company</td>
			<td>Catalog Number</td>
			<td>Comments</td>
		</tr>
		<tr>
			<td>Beam-Balance</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Beam</td>
			<td>home built</td>
			<td></td>
			<td>wood, 25&#34; l x 1&#34; h x 3/4&#34; w sealed with polyurethane varnish</td>
		</tr>
		<tr>
			<td>C-clamp</td>
			<td>Home Depot</td>
			<td>1422-C</td>
			<td>2 1/2&#34;</td>
		</tr>
		<tr>
			<td>barrier</td>
			<td>Home Depot</td>
			<td></td>
			<td>styrofoam, 18&#34; x 17 1/2&#34;</td>
		</tr>
		<tr>
			<td>table (for both BB &#38; BW)</td>
			<td>generic office supply</td>
			<td></td>
			<td>37&#34; h x 30&#34; w x 60&#34; l</td>
		</tr>
		<tr>
			<td>Name</td>
			<td>Company</td>
			<td>Catalog Number</td>
			<td>Comments</td>
		</tr>
		<tr>
			<td>Beam-Walk</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Beam</td>
			<td>home built</td>
			<td></td>
			<td>wood 38-1/2&#34; l x 1-3/4&#34; h x 1&#34; w sealed with polyurethane varnish (~ 37&#34; off floor)</td>
		</tr>
		<tr>
			<td>escape box</td>
			<td>home built</td>
			<td></td>
			<td>woodpainted black 12 1/2 &#34; l x 9&#34; h x 7-1/4&#34; w</td>
		</tr>
		<tr>
			<td>nails (pegs)</td>
			<td></td>
			<td></td>
			<td>2&#34;</td>
		</tr>
		<tr>
			<td>hinges</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>clamps</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>white noise machine</td>
			<td>San Diego Instruments 
			9155 Brown Deer Rd, Suite 8 San Diego, CA 92121 
			Phone: (858)530-2600</td>
			<td></td>
			<td>http://www.sandiegoinstruments.com/libraries/misc/datasheets/whitenoise.pdf</td>
		</tr>
		<tr>
			<td>light</td>
			<td>Home Depot</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Name</td>
			<td>Company</td>
			<td>Catalog Number</td>
			<td>Comments</td>
		</tr>
		<tr>
			<td>Morris Water Maze</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>fiberglass pool</td>
			<td>manufacturer unknown</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>(similar to one made by SDI)</td>
			<td>San Diego Instruments</td>
			<td>7000-0723</td>
			<td>72&#34; diameter x 30&#34; deep (~ 500 gal)</td>
		</tr>
		<tr>
			<td>plexiglass platform</td>
			<td>hand-made by Maggie Parsley</td>
			<td></td>
			<td>10 cm diameter, 26&#34; tall with silicone applied to the surface of the platform to provide a gripping surface</td>
		</tr>
		<tr>
			<td>(similar to one made by SDI)</td>
			<td>SDI</td>
			<td>7500-0272</td>
			<td></td>
		</tr>
		<tr>
			<td>plexiglass animal boxes w/ lids</td>
			<td>UTMB Machine Shop</td>
			<td></td>
			<td>2 boxes, 10&#34; w x 16&#34; L x 9&#34; h</td>
		</tr>
		<tr>
			<td>spot lights/ heat lamps</td>
			<td>Home Depot</td>
			<td></td>
			<td>3 around pool, 2 over boxes to dry animals</td>
		</tr>
		<tr>
			<td>AnyMaze</td>
			<td>San Diego Instruments 
			9155 Brown Deer Rd, Suite 8 San Diego, CA 92121 
			Phone: (858)530-2600</td>
			<td>/9001</td>
			<td>http://www.sandiegoinstruments.com/any-maze-video-tracking/</td>
		</tr>
	</tbody>
</table>

detecting behavioral deficits in rats after traumatic brain injury

外傷性脳損傷 (TBI) 両方の民間および軍事集団での増加率、TBI 今慢性的な疾病を考慮します。ただし、ほとんどの研究は、TBI の齧歯動物モデルにおける損傷の長期効果に します。ここでは、2 ヶ月までの 2 週間のような損傷後早期回 TBI の研究で確立された行動措置。これらのメソッドのいくつか以前で使用されている怪我後の後の時代まで非常に少数の研究所が 1 年間。ここでは、反射神経をテストするための短い神経学的評価、バランス、バランスとモーターの調整と赤字に敏感になることができますモリス水迷路のワーキング メモリーのバージョンをテストするビーム散歩をテストするビーム バランス メソッドを実証メモリを参照します。雄ラット処理され、バランス、神経学的に事前訓練を受けて、傍矢状洞流動打楽器の傷害 (FPI) または偽の傷害を受け取る前にモーターの調整をテストします。ラットは短い神経学的評価 (neuroscore)、ビーム バランスをテストすることができ・ ビーム歩行複数回水迷路のテスト中のみ一度。この違いは、ラットは、タスク、同じ動物でテストが試行を繰り返した場合、こうして結果を交絡を覚えることができるためです。1 受傷後 3 日からテスト、3 つの非認知タスクで有意差が検出された場合します。ただし、ビーム徒歩タスクの違い検出されなかった後時点で (後で 3 か月)。ビーム バランスで 3ヶ月と、neuroscore で 6 ヶ月で赤字が検出されました。傷害後、12 ヶ月ワーキング メモリの赤字を検出し、12 ヶ月でリファレンス ・ メモリに赤字が初めて登場しました。したがって、標準的な行動テストは FPI 後永続的な行動の赤字の有用な施策をすることができます。

Watch this Scientific Journal Video about Detecting Behavioral Deficits in Rats After Traumatic Brain Injury at JoVE.com

Detecting Behavioral Deficits in Rats After Traumatic Brain Injury

ここに示す行動テストの目的は、外傷性脳損傷後ラットにおける機能的障害を検出するためです。4 つの特定のテストは傷害の後の 1 年間に拡張する時特定の脳の領域への損傷を反映するように行動の赤字を検出するを掲載されています。

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, ...

detecting-behavioral-deficits-in-rats-after-traumatic-brain-injury

Nanyang Technological University

Research

JoVE Journal

Behavior

17.8K ビュー.  University of Texas Medical Branch. ここに示す行動テストの目的は、外傷性脳損傷後ラットにおける機能的障害を検出するためです。4 つの特定のテストは傷害の後の 1 年間に拡張する時特定の脳の領域への損傷を反映するように行動の赤字を検出するを掲載されています。

ビデオ: Detecting Behavioral Deficits in Rats After Traumatic Brain Injury

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

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

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

ビート難聴を暴く：同期指タッピングと知覚タイミングタスクを検出リズム障害

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

行動学

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 ...

Operant Procedures for Assessing Behavioral Flexibility in Rats

Executive functions consist of multiple high-level cognitive processes that drive rule generation and behavioral selection. An emergent property of these processes is the ability to adjust behavior in response to changes in one&#8217;s environment (i.e., behavioral flexibility). These processes are essential to normal human behavior, and may be disrupted in diverse neuropsychiatric conditions, including schizophrenia, alcoholism, depression, stroke, and Alzheimer&#8217;s disease. Understanding of the neurobiology of executive functions has been greatly advanced by the availability of animal tasks for assessing discrete components of behavioral flexibility, particularly strategy shifting and reversal learning. While several types of tasks have been developed, most are non-automated, labor intensive, and allow testing of only one animal at a time. The recent development of automated, operant-based tasks for assessing behavioral flexibility streamlines testing, standardizes stimulus presentation and data recording, and dramatically improves throughput. Here, we describe automated strategy shifting and reversal tasks, using operant chambers controlled by custom written software programs. Using these tasks, we have shown that the medial prefrontal cortex governs strategy shifting but not reversal learning in the rat, similar to the dissociation observed in humans. Moreover, animals with a neonatal hippocampal lesion, a neurodevelopmental model of schizophrenia, are selectively impaired on the strategy shifting task but not the reversal task. The strategy shifting task also allows the identification of separate types of performance errors, each of which is attributable to distinct neural substrates. The availability of these automated tasks, and the evidence supporting the dissociable contributions of separate prefrontal areas, makes them particularly well-suited assays for the investigation of basic neurobiological processes as well as drug discovery and screening in disease models.

The ability to assess executive functions such as behavioral flexibility in rats is useful for investigating the neurobiology of cognition in both intact animals and disease models. Here we describe automated tasks for assessing strategy shifting and reversal learning, which are particularly sensitive to disruptions in prefrontal cortical networks.

ラットの行動の柔軟性を評価するためのオペラント手順

Executive functions consist of multiple high-level cognitive processes that drive rule generation and behavioral selection. An emergent property of these ...

The Modified Hole Board - Measuring Behavior, Cognition and Social Interaction in Mice and Rats

This protocol describes the modified hole board (mHB), which combines features from a traditional hole board and open field and is designed to measure multiple dimensions of unconditioned behavior in small laboratory mammals (e.g., mice, rats, tree shrews and small primates). This paradigm is a valuable alternative for the use of a behavioral test battery, since a broad behavioral spectrum of an animal&#8217;s behavioral profile can be investigated in one single test.
The apparatus consists of a box, representing the &#8216;protected&#8217; area, separated from a group compartment. A board, on which small cylinders are staggered in three lines, is placed in the center of the box, representing the &#8216;unprotected&#8217; area of the set-up. The cognitive abilities of the animals can be measured by baiting some cylinders on the board and measuring the working and reference memory. Other unconditioned behavior, such as activity-related-, anxiety-related- and social behavior, can be observed using this paradigm. Behavioral flexibility and the ability to habituate to a novel environment can additionally be observed by subjecting the animals to multiple trials in the mHB, revealing insight into the animals&#8217; adaptive capacities.
Due to testing order effects in a behavioral test battery, na&#239;ve animals should be used for each individual experiment. By testing multiple behavioral dimensions in a single paradigm and thereby circumventing this issue, the number of experimental animals used is reduced. Furthermore, by avoiding social isolation during testing and without the need to food deprive the animals, the mHB represents a behavioral test system, inducing if any, very low amount of stress.

This protocol describes the modified hole board, which is a behavioral test set-up that comprises the characteristics of an open field and a traditional hole board. This set-up enables the differential analysis of unconditioned behavior of small laboratory mammals as well as the analysis of cognitive abilities.

変更された穴会は - マウスとラットにおける行動、認知と社会的相互作用を測定する

This protocol describes the modified hole board (mHB), which combines features from a traditional hole board and open field and is designed to measure ...

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

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

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

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

げっ歯類精神運動警戒試験（rPVT）：ラットとマウスの神経行動のパフォーマンスを評価するための方法

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

Assessing Spatial Memory Impairment in a Mouse Model of Traumatic Brain Injury Using a Radial Water Tread Maze

Despite the recent increase in use of mouse models in scientific research, researchers continue to use cognitive tasks that were originally designed and validated for rat use. The Radial Water Tread (RWT) maze test of spatial memory (designed specifically for mice and requiring no swimming) has been shown previously to successfully distinguish between controlled cortical impact-induced TBI mice and sham controls. Here, a detailed protocol for this task is presented. The RWT maze capitalizes on the natural tendency of mice to avoid open areas in favor of hugging the sides of an apparatus (thigmotaxis). The walls of the maze are lined with nine escape holes placed above the floor of the apparatus, and mice are trained to use visual cues to locate the escape hole that leads out of the maze. The maze is filled with an inch of cold water, sufficient to motivate escape but not deep enough to require that the mouse swim. The acquisition period takes only four training days, with a test of memory retention on day five and a long-term memory test on day 12. The results reported here suggest that the RWT maze is a feasible alternative to rat-validated, swimming-based cognitive tests in the assessment of spatial memory deficits in mouse models of TBI.

Here we present a protocol for a mouse-specific test of cognition that does not require swimming. This test can be used to successfully distinguish controlled cortical impact-induced traumatic brain injury mice from sham controls.

半径方向水迷路迷路を用いた外傷性脳損傷のマウスモデルにおける空間記憶障害の評価

Despite the recent increase in use of mouse models in scientific research, researchers continue to use cognitive tasks that were originally designed and ...

Using Laser Doppler Imaging and Monitoring to Analyze Spinal Cord Microcirculation in Rat

Laser Doppler flowmetry (LDF) is a noninvasive method for blood flow (BF) measurement, which makes it preferable for measuring microcirculatory alterations of the spinal cord. In this article, our goal was to use both Laser Doppler imaging and monitoring to analyze the change of BF after spinal cord injury. Both the laser Doppler image scanner and the probe/monitor were being employed to obtain each readout. The data of LDPI provided a local distribution of BF, which gave an overview of perfusion around the injury site and made it accessible for comparative analysis of BF among different locations. By intensely measuring the probing area over a period of time, a combined probe was used to simultaneously measure the BF and oxygen saturation of the spinal cord, showing overall spinal cord perfusion and oxygen supply. LDF itself has a few limitations, such as relative flux, sensitivity to movement, and biological zero signal. However, the technology has been applied in clinical and experimental study due to its simple setup and rapid measurement of BF.

Here we present a combination of laser Doppler perfusion imaging (LDPI) and laser Doppler perfusion monitoring (LDPM) to measure spinal cord local blood flows and oxygen saturation (SO2), as well as a standardized procedure for introducing spinal cord trauma on rat.

レーザーのドップラー イメージングおよび監視を使用したラット脊髄の微小循環の分析

Laser Doppler flowmetry (LDF) is a noninvasive method for blood flow (BF) measurement, which makes it preferable for measuring microcirculatory ...

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

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

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

恐怖のストレス強化学習、心的外傷後ストレス障害の堅牢な齧歯動物モデル

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

Novel Object Recognition and Object Location Behavioral Testing in Mice on a Budget

Ethologically relevant behavioral testing is a critical component of any study that uses mouse models to study the cognitive effects of various physiological or pathological changes. The object location task (OLT) and the novel object recognition task (NORT) are two effective behavioral tasks commonly used to reveal the function and relative health of specific brain regions involved in memory. While both of these tests exploit the inherent preference of mice for the novelty to reveal memory for previously encountered objects, the OLT primarily evaluates spatial learning, which relies heavily on hippocampal activity. The NORT, in contrast, evaluates non-spatial learning of object identity, which relies on multiple brain regions. Both tasks require an open-field-testing arena, objects with equivalent intrinsic value to mice, appropriate environmental cues, and video recording equipment and the software. Commercially available systems, while convenient, can be costly. This manuscript details a simple, cost-effective method for building the arenas and setting up the equipment necessary to perform the OLT and NORT. Furthermore, the manuscript describes an efficient testing protocol that incorporates both OLT and NORT and provides typical methods for data acquisition and analysis, as well as representative results. Successful completion of these tests can provide valuable insight into the memory function of various mouse model systems and appraise the underlying neural regions that support these functions.

Here we provide a protocol which includes comprehensive instructions for the economical establishment of murine object location and novel object recognition behavioral testing, including the design, cost, and construction of required equipment as well as execution of behavioral testing, data collection, and analysis.

新規オブジェクト認識と行動の予算上のマウスでテスト オブジェクトの場所

Ethologically relevant behavioral testing is a critical component of any study that uses mouse models to study the cognitive effects of various ...

Assessing the Autonomic and Behavioral Effects of Passive Motion in Rats using Elevator Vertical Motion and Ferris-Wheel Rotation

The overall goal of this study is to assess the autonomic and behavioral effects of passive motion in rodents using the elevator vertical motion and Ferris-wheel rotation devices. These assays can help confirm the integrity and normal functioning of the autonomic nervous system. They are coupled to quantitative measures based on defecation counting, open-field examination, and balance beam crossing. The advantages of these assays are their simplicity, reproducibility, and quantitative behavioral measures. The limitations of these assays are that the autonomic reactions could be epiphenomena of non-vestibular disorders and that a functioning vestibular system is required. Examination of disorders such as motion sickness will be greatly aided by the detailed procedures of these assays.

Protocols are presented to assess the autonomic and behavioral effects of passive motion in rodents using elevator vertical motion and Ferris-wheel rotation.

エレベーター垂直運動と観覧車回転を用いたラットにおける受動運動の自律性と行動の影響の評価

The overall goal of this study is to assess the autonomic and behavioral effects of passive motion in rodents using the elevator vertical motion and ...