この研究は、臨床神経科学保健研究委員会、ジストニア アイルランド科学財団アイルランド、アイルランド研究所からの助成金によって支えられました。

セントビン セントの大学病院、ダブリンの医学研究倫理委員会が説明されたプロトコルに参加する頸部ジストニア、彼らの兄弟姉妹 (ジストニアを受けない) と健全な制御と患者の募集のための承認を与えた以下に。

1. ハードウェアとソフトウェア ソリューション
注: 2 つのハードウェア オプションは、正確な刺激間間隔で視覚刺激を表示する開発されています。両方は設計され、バイオ エンジニア リング、トリニティ ・ カレッジ ・ ダブリンの三位一体の中心部で自社で開発された、前述5,16をされています。ここで使用される正確なハードウェア ソリューションを複製したい方々 は、バイオ エンジニア リングの三位一体の中心部に直接連絡して同じを求めることができます。また、ヘッドセットのため 3 D 印刷ファイル、添付の Arduino マイコン等の指示を含む命令の完全なセット。http://www.dystoniaresearch.ie/temporal-discrimination-threshold/ からダウンロードできます。光発光ダイオード (LED) を制御するのパラレル ポート経由でデスクトップ コンピューターにインストールされている、プログラム (例えば、神経システム)、プレゼンテーションでのカスタム プログラムを使用して生成されるテーブル トップ アプローチで提示刺激コンピューター。また、下記のとおり、テーブル トップの Led は Arduino マイコンを介して制御できます。プレゼンテーション コードと Arduino ファイルが上記のリンクからダウンロードできるも。
<ol><li>TDT ハードウェア: テーブル トップ メソッド<ol>
<li>'X'、注視点として黒マットまたは参加者の前にテーブルに置かれたシート上をマークします。</li>
		<li>参加者に、彼らは固定ポイントの目の前に座っているので、自分の位置を求めます。</li>
		<li>参加者の前でテーブルの上の箱に収められ黄色発光ダイオード (LED) ペア (直径 5 mm, 90 cd/m2の輝度) を配置します。</li>
		<li>必要に応じて Led は垂直方向に調整し、左側と右側、上の被写体の中心点から 7 ° に配置するように、ボックスを合わせます。</li>
		<li>暗い部屋でこの実験を行います。少量背景輝度の実験の実行に十分な演算子を有効にする必要があります。</li>
		<li>常時注視点に焦点を当てるし、点滅している Led を直接見ない参加者に指示します。</li>
		<li>LED ボックスにマイコンを接続し、次の例えば、マイクロ コント ローラー ボックスの液晶ディスプレイに表示される指示がプレゼンテーション方法を選択する画面に表示される: 'random' または '階段' と選択モード: '左 ' トップ最初、など.</li>
		<li>同期または非同期にする刺激を知覚するかどうかに応じて各刺激対の「同じ」または「別の」次のプレゼンテーションに対応するように参加者を求めます。</li>
		<li>各試行が開始、発声によって参加者に通知、画面 5-0 秒からカウント ダウン。</li>
	</ol>
</li>
</ol><img alt="Figure 1" class="xfigimg" src="/files/ftp_upload/56310/56310fig1.jpg"> 図 1: ヘッドセットのデザインの (a) の模式図。黄色 Led (直径 5 mm) のペアと赤固定 LED (直径 3 mm) はヘッド マウント ユニットを介して参加者の左右に配置、目の前の鏡に反射を経由して表示しました。(ヘッドセットの b) の 3 D モデル。ヘッドセットは、レーザー焼結ナイロン プラスチックから開発された、重量 0.70 kg、透明度の低いインデックスを持つ、光の浸透を最小限に抑えるために色は黒です。(と b) バトラーらからのわずかな変更で再現されています。16 IOP 発行の許可を得ています。(c) テーブル トップ プレゼンテーション用 LED 刺激ボックス。
<ol start="2"><li>TDT ハードウェア: TDT の携帯用ヘッドセット<ol>
<li>任意の適切な場所で実験を行います。</li>
		<li>ヘッドセットとフォローにマイコンを接続、例えば、マイクロ コント ローラー ボックスの液晶ディスプレイに表示される指示がプレゼンテーション方法を選択する画面に表示される: 'random' または '階段' とモード: '左 ' トップ最初、等。</li>
		<li>彼らの前にテーブルの上の肘を自分の位置に参加者を直接します。自分たちの手でデバイスを保持する、直接接眼レンズをそれにより周囲ゴム シールに自分の顔をゆっくり周囲の光を用シール。</li>
		<li>すべての回で赤固定 LED に焦点を当てるし、点滅 Led を直接見ない参加者に指示します。</li>
		<li>同期または非同期にする刺激を知覚するかどうかに応じて各刺激対の「同じ」または「別の」次のプレゼンテーションに対応するように参加者を求めます。</li>
		<li>各試行が開始、発声によって参加者に通知、画面 5-0 秒からカウント ダウン。</li>
	</ol>
</li>
</ol>2. 刺激提示
注: 刺激呈示する 2 つの方法が採用されています。
<ol><li>ステアケース法<ol>
<li>Select '階段' プレゼンテーション;刺激が表示されますすべての 5 の刺激間間隔が 0 から開始して、徐々 に非同期 (増 5 ms) になるたびに。</li>
		<li>4 つのプレゼンテーション形式のいずれかを選択: (i) 左上 LED 最初 (ii) 左下最初 (iii) 右上 LED に最初に、または (iv) 右下の LED は最初。</li>
		<li>2.1.2 のステップを繰り返して、各モダリティを 2 回、合計 8 回の実行の結果実行は。</li>
		<li>参加者応答「異なる」刺激の 3 つの連続したペアのときは、試験を終了します。</li>
	</ol>
</li>
	<li>ランダム表示方法<ol>
<li>Select 'ランダム' プレゼンテーション;刺激のペアが表示されますすべての 5 s。0-100 からの無作為の方法で、刺激間間隔の幅 ms。</li>
		<li>4 つのプレゼンテーション形式のいずれかを選択: (i) 左上 LED 最初 (ii) 左下最初 (iii) 右上 LED に最初に、または (iv) 右下の LED は最初。</li>
		<li>2.2.2 のステップを繰り返して、各モダリティを 2 回、合計 8 回の実行の結果実行は。 注: 各実行は同じ長さである、自動的に完了します。</li>
	</ol>
</li>
</ol>3. データ分析
<ol><li>単一の TDT 値<ol>
<li>ステアケース法からデータを使用して、各 8 回の実行の最後の 3 つの「別の」応答の最初を強調表示します。これらは、それぞれの実行のしきい値です。</li>
		<li>撮影から彼らの 8 回の実行の各閾値の中央値によって各参加者の時間弁別閾 (TDT) を計算します。個人ごとの単一の TDT 値 (単位はミリ秒) の結果。</li>
		<li>各参加者の Zスコアを計算します。年齢をマッチさせた対照人口から参加者の TDT と TDT の平均の差として Zスコアを定義 (<img alt="Equaiton 1" src="/files/ftp_upload/56310/56310eq1.jpg">、制御の人口の TDT 値の標準偏差で割った値、 <img alt="Equaiton 2" src="/files/ftp_upload/56310/56310eq2.jpg"> </img>。 <img alt="Equaiton 3" src="/files/ftp_upload/56310/56310eq3.jpg">
</li>
		<li>TDT の正常または異常であるかどうかを決定します。Zスコア≥ 2.5 は異常 TDT を反映するようにみなされます。</li>
	</ol>
</li>
	<li>分布解析<ol>
<li>「同じ」に対応する '0' と '1' は「異なる」、表 1に対応するよう、応答データをエンコード ステアケース法からデータを使用して、します。</li>
		<li>Http://www.dystoniaresearch.ie/temporal-discrimination-threshold/ から下記分布解析を実行する無料 MATLAB.exe をダウンロードします。執事らを参照してください。このメソッドの完全な説明のための16 。また、下記のとおり進んでください。</li>
		<li>すべての実行が最長の長さと同じことを確認するデータを埋めます。これは次の実行の終了すべてのそれに続く応答が"different"と仮定すると、テーブルの 1(b)。</li>
		<li>各参加者は、表 1(c)の試験で平均応答は。これは、刺激の非同期の関数としてプロットできます。</li>
		<li>累積的なガウス関数でこの平均値または代表的なデータをフィットします。この分布の平均は、参加者が「同じ」または「別の」応答するしくするポイントを表します。この点を「主観的等価点」と呼びます (PSE)。ガウス分布の標準偏差に 'ちょうど顕著な違い' とも呼ばれます (JND)、どのように敏感な参加者を示す時間的不一致性の平均の周りに変化が。</li>
		<li>TDT と PSE と心理、累積的なガウス関数の JND の 95% 信頼区間を推定するために非パラメトリック ブートス トラップ プロシージャにデータを提出することにより分析を拡張します。これを行うには、交換元の応答からテーブル 1(b)、時間ステップごとにランダム サンプリングによって新しい代表的なデータのセットを生成します。TDT を計算し、それぞれの代表的なデータセットの16の新しい心理機能に合わせてください。</li>
		<li>対数尤度比、16,17を使用して各参加者のフィット、または逸脱 (D) の良さを計算します。 <img alt="Equaiton 4" src="/files/ftp_upload/56310/56310eq4.jpg"> Kはタイム ポイントの数、 nは私が時点、(4 つの権利・ 4 左) 一般に 8 つの繰返し、 yは私の繰り返しの数は、非同期応答の観測の割合p私は、非同期応答の近似曲線を予測の割合です。逸脱値 0 を意味完璧にフィットします。</li>
		<li>結果をプロットします。 注: 階段表示方法から生じるデータの上記のセクション 3 で説明したように単一または分散 TDT を決定するランダムなプレゼンテーションのアプローチからのデータを分析できます。しかし、刺激間間隔のランダム順序は、ためこれらのデータする必要があります (最大最小刺激間間隔) から注文する最初、分析を開始する前に上記、表 2。さらに、次のランダムなプレゼンテーションとして、既定では、すべての実行が等しい長さのデータを埋め込む必要はありません。</li>
	</ol>
</li>
</ol>

<ol>
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レベッカ B ベック、イーバン ・ M Mc 支配、ジョン ・ バトラー、dorina 上 Birsanu、ブレンダン ・ キリンヴァン、イネスのバイザー、シュルティ ナラシムハム資金調達、財務情報開示または宣言する利害の衝突があるないです。マイケル ・ ハッチンソンは、ジストニア アイルランド、健康研究委員会の (CSA-2012-5)、ジストニア研究 (ベルギー) とアイルランド臨床神経科学研究所の財団から研究助成金を受け取ります。ショーン O'リオーダン報告受信スピーカー'Abbvie から s 謝礼。リチャード ・ ライリーがエンタープライズ アイルランド科学財団から資金を受け取るとアイルランドの健康研究会。

TDT 測定と解析
刺激の提示に使用する装置 (テーブル トップとヘッドセット) 2 つの方法の 2 つのフォーム (階段とランダム) とデータ分析に 2 つのアプローチ (伝統的なと分布) が提案されている測定し、人を数値化する方法の時間を示すために弁別能力。携帯用のヘッドセットは、ながら、任意の便利な場所で収集するデータの距離と参加者と LED 光源の角度...

時間弁別課題では、差別、または彼らの環境の急速な変化を感知する人の能力について説明します。時間弁別閾 (TDT) は、個人が 2 つの連続した感覚刺激が非同期を認識できる最短の時間間隔です。大脳基底核は、ジストニア1,2,3,4,5,6などに影響を与える疾患に延長される異常時間弁別課題が示されています。,7。
ジストニアは三番目ほとんどの共通の神経学的な運動障害 -'パーキンソン病と本態性振戦です。それは持続的または断続的な筋肉の収縮異常、しばしば反復的な動きやポーズ8原因が特徴です。ジストニア、体のどの部分に影響を与えることができます。1 つの身体の部分に影響を与える場合は、ジストニア8と呼ばれます。ジストニア首の筋肉に影響を与える頚部ジストニアと呼ばれる、成人発症特発性分離ジストニアの最も一般的な表現です。9,10頸部ジストニアの病態は不明で。それは優性遺伝と著しく減らされた浸透遺伝的疾患であると見なされます。環境要因はまた病気の浸透度と表現に関連して重要であると見なされます。
丘、背側の中脳にある感覚構造秘密注意配向2,11,12過程で環境刺激の迅速な検出が重要です。視覚は、網膜蓋経路を通じて急速に丘をアクセスします。TDT は、上丘の浅層における視覚 (と他の感覚刺激) の処理を表すと考えられている単純な客観的指標です。TDT は頸部ジストニアは、影響を受けない親戚や健常者の参加者を持つ個人で研究されています。年齢と性別をマッチさせたコントロール群と比較して、異常な TDT は高感度 (97%、37 例の 36) と頸部ジストニア1の特異性 (98-100%)。常染色体優性遺伝13,と浸透度を年齢と性差を示す (14 25、48 歳またはより古い) 頸部ジストニア患者の影響を受けない第一女性親族の 50% に発見されて異常 TDT14. (通常 TDTs と親戚に比較して) 頸部ジストニア患者の影響を受けない親戚の異常 TDT (ボクセル ベース形態) によって増大した被殻15に関連付けられ、(fMRI) による被殻の活動の低下4.上丘は、頸部ジストニア12の機能不全は、神経細胞のネットワークの重要なノードと見なされます。時間弁別課題の評価は、その基になる頸部ジストニアの重要な手がかりを提供するとみなされます。
この記事の目的は、測定時間弁別課題の分析と頸部ジストニアの病態生理を研究するこのメソッドのアプリケーションを示す 2 つの方法を提示することです。

<table border="0" cellpadding="0" cellspacing="0" width="1057">
	<tbody>
		<tr height="86">
			<td height="86" style="height:87px;width:216px;">TDT head set</td>
			<td style="width:555px;">Can be supplied by Trinity Centre for Bioengineering, Trinity College Dublin.&#160; Alternatively full instructions are available for free download from http://www.dystoniaresearch.ie/temporal-discrimination-threshold/</td>
			<td style="width:119px;">1</td>
			<td style="width:167px;">A custom-built, portable device for the presentation of visual stimuli.</td>
		</tr>
		<tr height="82">
			<td height="82" style="height:83px;width:216px;">TDT table top LED box</td>
			<td style="width:555px;">Can be supplied by Trinity Centre for Bioengineering, Trinity College Dublin.&#160; Alternatively full instructions are available for free download from http://www.dystoniaresearch.ie/temporal-discrimination-threshold/</td>
			<td style="width:119px;">2</td>
			<td>A custom-built, table-top device for the presentation of visual stimuli.</td>
		</tr>
		<tr height="88">
			<td height="88" style="height:89px;width:216px;">Microcontroller</td>
			<td style="width:555px;">Can be supplied by Trinity Centre for Bioengineering, Trinity College Dublin.&#160; Alternatively full instructions are available for free download from http://www.dystoniaresearch.ie/temporal-discrimination-threshold/</td>
			<td style="width:119px;">3</td>
			<td>A custom-built microcontroller for the delivery of visual stimuli in staircase or random order, with precise inter-stimulus intervals.</td>
		</tr>
	</tbody>
</table>

measurement &amp; analysis of the temporal discrimination threshold applied to cervical dystonia

時間弁別閾 (TDT) は、オブザーバーは、2 つ連続の刺激として非同期 (通常 30-50 ms) を識別できる最短の時間間隔です。(長期) の頸部ジストニア、成人発症特発性分離ジストニアの表現型を含む神経の疾患には異常に示されています。TDT は急激な環境の変化を察知する能力の定量化、丘、ひそかな注意定位でキー ノードの視覚ニューロンの動作を示すものであります。この記事は、TDT の (刺激提示の 2 つのモード、2 つのハードウェア オプションなど) を測定する方法を設定します。また、データ分析と TDT 計算の 2 つのアプローチを探ります。頸部ジストニアと成人発症特発性分離ジストニアの病態に関する理解に時間弁別行動評価尺度の活用、また説明します。

事例いっぱいスコアリング ・ シートはテーブル 1 と 2、これらはそれぞれ次の階段とランダムな刺激呈示方法の結果を表す提供されます。各実行のしきい値 (のタイミング刺激の 3 つのペアの最初の' '異なるとみなされる) が強調表示されます。テーブル 1TDT は 25 ms (すなわち40、25、25、25、45、25、40、10 ms の?...

Watch this Scientific Journal Video about Measurement & Analysis of the Temporal Discrimination Threshold Applied to Cervical Dystonia at JoVE.com

Measurement & Analysis of the Temporal Discrimination Threshold Applied to Cervical Dystonia

測定の時間弁別閾値の解析方法、示され、頸部ジストニアの病態に関する研究への応用については、説明します。

測定・頸部ジストニアに適用される時間の弁別閾値の解析

The temporal discrimination threshold (TDT) is the shortest time interval at which an observer can discriminate two sequential stimuli as being ...

measurement-analysis-temporal-discrimination-threshold-applied-to

Research

JoVE Journal

Neuroscience

Measurement &amp; Analysis of the Temporal Discrimination Threshold Applied to Cervical Dystonia

9.7K ビュー.  Trinity College Dublin, The University of Dublin. 測定の時間弁別閾値の解析方法、示され、頸部ジストニアの病態に関する研究への応用については、説明します。

ビデオ: Measurement & Analysis of the Temporal Discrimination Threshold Applied to Cervical Dystonia

T-maze Forced Alternation and Left-right Discrimination Tasks for Assessing Working and Reference Memory in Mice

Forced alternation and left-right discrimination tasks using the T-maze have been widely used to assess working and reference memory, respectively, in rodents. In our laboratory, we evaluated the two types of memory in more than 30 strains of genetically engineered mice using the automated version of this apparatus. Here, we present the modified T-maze apparatus operated by a computer with a video-tracking system and our protocols in a movie format. The T-maze apparatus consists of runways partitioned off by sliding doors that can automatically open downward, each with a start box, a T-shaped alley, two boxes with automatic pellet dispensers at one side of the box, and two L-shaped alleys. Each L-shaped alley is connected to the start box so that mice can return to the start box, which excludes the effects of experimenter handling on mouse behavior. This apparatus also has an advantage that in vivo microdialysis, in vivo electrophysiology, and optogenetics techniques can be performed during T-maze performance because the doors are designed to go down into the floor. In this movie article, we describe T-maze tasks using the automated apparatus and the T-maze performance of &alpha;-CaMKII+/- mice, which are reported to show working memory deficits in the eight-arm radial maze task. Our data indicated that &alpha;-CaMKII+/- mice showed a working memory deficit, but no impairment of reference memory, and are consistent with previous findings using the eight-arm radial maze task, which supports the validity of our protocol. In addition, our data indicate that mutants tended to exhibit reversal learning deficits, suggesting that &alpha;-CaMKII deficiency causes reduced behavioral flexibility. Thus, the T-maze test using the modified automatic apparatus is useful for assessing working and reference memory and behavioral flexibility in mice.

This article presents the protocol of T-maze tests using a modified automated apparatus for assessing the learning and memory functions in mice.

マウスで作業していて、メモリの参照を評価するためのT-迷路強制交替と左右弁別課題

Forced alternation and left-right discrimination tasks using the T-maze have been widely used to assess working and reference memory, respectively, in ...

神経科学

Rapid Determination of the Thermal Nociceptive Threshold in Diabetic Rats

Painful diabetic neuropathy (PDN) is characterized by hyperalgesia i.e., increased sensitivity to noxious stimulus, and allodynia i.e., hypersensitivity to normally innocuous stimuli1. Hyperalgesia and allodynia have been studied in many different rodent models of diabetes mellitus2. However, as stated by B&ouml;lcskei et al, determination of "pain" in animal models is challenging due to its subjective nature3. Moreover, the traditional methods used to determine behavioral responses to noxious thermal stimuli usually lack reproducibility and pharmacological sensitivity3. For instance, by using the hot-plate method of Ankier4, flinch, withdrawal and/or licking of either hind- and/or fore-paws is quantified as reflex latencies at constant high thermal stimuli (52-55 &deg;C). However, animals that are hyperalgesic to thermal stimulus do not reproducibly show differences in reflex latencies using those supra-threshold temperatures3,5. As the recently described method of B&ouml;lcskei et al.6, the procedures described here allows for the rapid, sensitive and reproducible determination of thermal nociceptive thresholds (TNTs) in mice and rats. The method uses slowly increasing thermal stimulus applied mostly to the skin of mouse/rat plantar surface. The method is particularly sensitive to study anti-nociception during hyperalgesic states such as PDN. The procedures described bellow are based on the ones published in detail by Alm&aacute;si et al 5 and B&ouml;lcskei et al 3. The procedures described here have been approved the Laboratory Animal Care and Use Committee (LACUC), Wright State University.

Here, we describe a rapid reliable and simple procedure to determine the lowest temperature at which rats or mice show nocifensive behavior, i.e. the thermal nociceptive threshold (TNT). This method applies a slowly increasing thermal stimulus allowing precise and reproducible estimation of TNTs with minimum, if any, stress to the animals.

糖尿病ラットの熱侵害受容閾値の迅速定量

Painful diabetic neuropathy (PDN) is characterized by hyperalgesia i.e., increased sensitivity to noxious stimulus, and allodynia i.e., hypersensitivity ...

A Galvanotaxis Assay for Analysis of Neural Precursor Cell Migration Kinetics in an Externally Applied Direct Current Electric Field

The discovery of neural stem and progenitor cells (collectively termed neural precursor cells) (NPCs) in the adult mammalian brain has led to a body of research aimed at utilizing the multipotent and proliferative properties of these cells for the development of neuroregenerative strategies. A critical step for the success of such strategies is the mobilization of NPCs toward a lesion site following exogenous transplantation or to enhance the response of the endogenous precursors that are found in the periventricular region of the CNS. Accordingly, it is essential to understand the mechanisms that promote, guide, and enhance NPC migration. Our work focuses on the utilization of direct current electric fields (dcEFs) to promote and direct NPC migration - a phenomenon known as galvanotaxis. Endogenous physiological electric fields function as critical cues for cell migration during normal development and wound repair. Pharmacological disruption of the trans-neural tube potential in axolotl embryos causes severe developmental malformations1. In the context of wound healing, the rate of repair of wounded cornea is directly correlated with the magnitude of the epithelial wound potential that arises after injury, as shown by pharmacological enhancement or disruption of this dcEF2-3. We have demonstrated that adult subependymal NPCs undergo rapid and directed cathodal migration in vitro when exposed to an externally applied dcEF. In this protocol we describe our lab's techniques for creating a simple and effective galvanotaxis assay for high-resolution, long-term observation of directed cell body translocation (migration) on a single-cell level. This assay would be suitable for investigating the mechanisms that regulate dcEF transduction into cellular motility through the use of transgenic or knockout mice, short interfering RNA, or specific receptor agonists/antagonists.

In this protocol we demonstrate how to construct custom chambers that permit the application of a direct current electric field to enable time-lapse imaging of adult brain derived neural precursor cell translocation during galvanotaxis.

外部から印加された直流電界における神経前駆細胞の移行動態の解析のための走電性アッセイ

The discovery of neural stem and progenitor  cells (collectively termed neural precursor cells) (NPCs) in the adult  mammalian brain has led to a body of ...

The Dig Task: A Simple Scent Discrimination Reveals Deficits Following Frontal Brain Damage

Cognitive impairment is the most frequent cause of disability in humans following brain damage, yet the behavioral tasks used to assess cognition in rodent models of brain injury is lacking. Borrowing from the operant literature our laboratory utilized a basic scent discrimination paradigm1-4 in order to assess deficits in frontally-injured rats. Previously we have briefly described the Dig task and demonstrated that rats with frontal brain damage show severe deficits across multiple tests within the task5. Here we present a more detailed protocol for this task. Rats are placed into a chamber and allowed to discriminate between two scented sands, one of which contains a reinforcer. The trial ends after the rat either correctly discriminates (defined as digging in the correct scented sand), incorrectly discriminates, or 30 sec elapses. Rats that correctly discriminate are allowed to recover and consume the reinforcer. Rats that discriminate incorrectly are immediately removed from the chamber. This can continue through a variety of reversals and novel scents. The primary analysis is the accuracy for each scent pairing (cumulative proportion correct for each scent). The general findings from the Dig task suggest that it is a simple experimental preparation that can assess deficits in rats with bilateral frontal cortical damage compared to rats with unilateral parietal damage. The Dig task can also be easily incorporated into an existing cognitive test battery. The use of more tasks such as this one can lead to more accurate testing of frontal function following injury, which may lead to therapeutic options for treatment. All animal use was conducted in accordance with protocols approved by the Institutional Animal Care and Use Committee.

In this protocol, a novel application of scent discrimination is described. The Dig task is a reasonably inexpensive task that can be used to assess frontally-mediated cognition following brain damage.

ディグタスク：シンプル香り差別は前頭葉脳損傷後の赤字を明かす

Cognitive impairment is the most frequent cause of disability in humans following brain damage, yet the behavioral tasks used to assess cognition in ...

A Comprehensive Protocol for Manual Segmentation of the Medial Temporal Lobe Structures

The present paper describes a comprehensive protocol for manual tracing of the set of brain regions comprising the medial temporal lobe (MTL): amygdala, hippocampus, and the associated parahippocampal regions (perirhinal, entorhinal,&#160;and parahippocampal proper). Unlike most other tracing protocols available, typically focusing on certain MTL areas (e.g., amygdala and/or hippocampus), the integrative perspective adopted by the present tracing guidelines allows for clear localization of all MTL subregions. By integrating information from a variety of sources, including extant tracing protocols separately targeting various MTL structures, histological reports, and brain atlases, and with the complement of illustrative visual materials, the present protocol provides an accurate, intuitive, and convenient guide for understanding the MTL anatomy. The need for such tracing guidelines is also emphasized by illustrating possible differences between automatic and manual segmentation protocols. This knowledge can be applied toward research involving not only structural MRI investigations but also structural-functional colocalization and fMRI signal extraction from anatomically defined ROIs, in healthy and clinical groups alike.

The present work provides a comprehensive set of guidelines for manually tracing the medial temporal lobe (MTL) structures. This protocol can be applied to research involving structural and/or combined structural-functional magnetic resonance imaging (MRI) investigations of the MTL, in both healthy and clinical groups.

内側側頭葉構造の手動分割のための総合的なプロトコル

The present paper describes a comprehensive protocol for manual tracing of the set of brain regions comprising the medial temporal lobe (MTL): amygdala, ...

High-throughput Analysis of Mammalian Olfactory Receptors: Measurement of Receptor Activation via Luciferase Activity

Odorants create unique and overlapping patterns of olfactory receptor activation, allowing a family of approximately 1,000 murine and 400 human receptors to recognize thousands of odorants. Odorant ligands have been published for fewer than 6% of human receptors1-11. This lack of data is due in part to difficulties functionally expressing these receptors in heterologous systems. Here, we describe a method for expressing the majority of the olfactory receptor family in Hana3A cells, followed by high-throughput assessment of olfactory receptor activation using a luciferase reporter assay. This assay can be used to (1) screen panels of odorants against panels of olfactory receptors; (2) confirm odorant/receptor interaction via dose response curves; and (3) compare receptor activation levels among receptor variants. In our sample data, 328 olfactory receptors were screened against 26 odorants. Odorant/receptor pairs with varying response scores were selected and tested in dose response. These data indicate that a screen is an effective method to enrich for odorant/receptor pairs that will pass a dose response experiment, i.e. receptors that have a bona fide response to an odorant. Therefore, this high-throughput luciferase assay is an effective method to characterize olfactory receptors&#8212;an essential step toward a model of odor coding in the mammalian olfactory system.

Olfactory receptor activation patterns encode odor identity, but the lack of published data identifying odorant ligands for mammalian olfactory receptors hinders the development of a comprehensive model of odor coding. This protocol describes a method to facilitate high-throughput identification of olfactory receptor ligands and quantification of receptor activation.

ルシフェラーゼ活性を介し受容体活性化の測定：哺乳類嗅覚受容体のハイスループット分析

Odorants create unique and overlapping patterns of olfactory receptor activation, allowing a family of approximately 1,000 murine and 400 human receptors ...

Diffusion Imaging in the Rat Cervical Spinal Cord

Magnetic resonance imaging (MRI) is the state of the art approach for assessing the status of the spinal cord noninvasively, and can be used as a diagnostic and prognostic tool in cases of disease or injury. Diffusion weighted imaging (DWI), is sensitive to the thermal motion of water molecules and allows for inferences of tissue microstructure. This report describes a protocol to acquire and analyze DWI of the rat cervical spinal cord on a small-bore animal system. It demonstrates an imaging setup for the live anesthetized animal and recommends a DWI acquisition protocol for high-quality imaging, which includes stabilization of the cord and control of respiratory motion. Measurements with diffusion weighting along different directions and magnitudes (b-values) are used. Finally, several mathematical models of the resulting signal are used to derive maps of the diffusion processes within the spinal cord tissue that provide insight into the normal cord and can be used to monitor injury or disease processes noninvasively.

The goal of this protocol is to obtain high-quality diffusion weighted magnetic resonance imaging (DWI) of the rat spinal cord for noninvasive characterization of tissue microstructure. This protocol describes optimizations of the MRI sequence, radiofrequency coil, and analysis methods to enable DWI images free from artifacts.

ラット頸部脊髄の拡散イメージング

Magnetic resonance imaging (MRI) is the state of the art approach for assessing the status of the spinal cord noninvasively, and can be used as a ...

In Vitro Modeling of Cancerous Neural Invasion: The Dorsal Root Ganglion Model

One way that solid tumors disseminate is through neural invasion. This route is well-known in cancers of the head and neck, prostate, and pancreas. These neurotropic cancer cells have a unique ability to migrate unidirectionally along nerves towards the central nervous system (CNS). The dorsal root ganglia (DRG)/cancer cell model is a three dimensional (3D) in vitro model frequently used for studying the interaction between neural stroma and cancer cells. In this model, mouse or human cancer cell lines are grown in ECM adjacent to preparations of freshly dissociated cultured DRG. In this article, the DRG isolation protocol from mice, and implantation in petri dishes for co-culturing with pancreatic cancer cells are demonstrated. Five days after implantation, the cancer cells made contact with the DRG neurites. Later, these cells formed bridgeheads to facilitate more extensive polarized, neurotropic migration of cancer cells.

In Vitro Modeling of Cancerous Neural Invasion: The Dorsal Root Ganglion Model

This video article shows the use of the dorsal root ganglia (DRG)/cancer cell model in pancreatic ductal adenocarcinoma.

後根神経節モデル：癌性神経浸潤のin vitroモデルでは

One way that solid tumors disseminate is through neural invasion. This route is well-known in cancers of the head and neck, prostate, and pancreas. These ...

An Objective and Reproducible Test of Olfactory Learning and Discrimination in Mice

Olfaction is the predominant sensory modality in mice and influences many important behaviors, including foraging, predator detection, mating, and parenting. Importantly, mice can be trained to associate novel odors with specific behavioral responses to provide insight into olfactory circuit function. This protocol details the procedure for training mice on a Go/No-Go operant learning task. In this approach, mice are trained on hundreds of automated trials daily for 2&#8211;4 weeks and can then be tested on novel Go/No-Go odor pairs to assess olfactory discrimination, or be used for studies on how odor learning alters the structure or function of the olfactory circuit. Additionally, the mouse olfactory bulb (OB) features ongoing integration of adult-born neurons. Interestingly, olfactory learning increases both the survival and synaptic connections of these adult-born neurons. Therefore, this protocol can be combined with other biochemical, electrophysiological, and imaging techniques to study learning and activity-dependent factors that mediate neuronal survival and plasticity.

Here, we train mice on an associative learning task to test odor discrimination. This protocol also allows for studies on learning-induced structural changes in the brain.

嗅覚学習とマウスにおける差別の客観的かつ再現性のあるテスト

Olfaction is the predominant sensory modality in mice and influences many important behaviors, including foraging, predator detection, mating, and ...

The Power of Interstimulus Interval for the Assessment of Temporal Processing in Rodents

Temporal processing deficits have been implicated as a potential elemental dimension of higher-level cognitive processes, commonly observed in neurocognitive disorders. Despite the popularization of prepulse inhibition (PPI) in recent years, many current protocols promote using a percent of control measure, thereby precluding the assessment of temporal processing. The present study used cross-modal PPI and gap prepulse inhibition (gap-PPI) to demonstrate the benefits of employing a range of interstimulus intervals (ISIs) to delineate effects of sensory modality, psychostimulant exposure, and age. Assessment of sensory modality, psychostimulant exposure, and age reveals the utility of an approach varying the interstimulus interval (ISI) to establish the shape of the ISI function, including increases (sharper curve inflections) or decreases (flattening of the response amplitude curve) in startle amplitude. Additionally, shifts in peak response inhibition, suggestive of a differential sensitivity to the manipulation of ISI, are often revealed. Thus, the systematic manipulation of ISI affords a critical opportunity to evaluate temporal processing, which may reveal the underlying neural mechanisms involved in neurocognitive disorders.

Temporal processing, a preattentive process, may underlie deficits in higher-level cognitive processes, including attention, commonly observed in neurocognitive disorders. Using prepulse inhibition as an exemplar paradigm, we present a protocol for manipulating interstimulus interval (ISI) to establish the shape of the ISI function to provide an assessment of temporal processing.