この研究のための資金は、ガーネットパスとロドニー·ウィリアムズ記念財団とラ·トローブ大学によって提供されました。

<ol>
	<li>Mauger, S. J., Shivdasani, M. N., Rathbone, G. D., Argent, R. E., Paolini, A. G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=An+in+vivo+investigation+of+first+spike+latencies+in+the+inferior+colliculus+in+response+to+multichannel+penetrating+auditory+brainstem+implant+stimulation.">An in vivo investigation of first spike latencies in the inferior colliculus in response to multichannel penetrating auditory brainstem implant stimulation.</a> Journal of Neural Engineering. 7, 036004-036004 (2010).</li><li>Shivdasani, M. N., Mauger, S. J., Argent, R. E., Rathbone, G. D., Paolini, A. G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Inferior+colliculus+responses+to+dual-site+intralamina+stimulation+in+the+ventral+cochlear+nucleus.">Inferior colliculus responses to dual-site intralamina stimulation in the ventral cochlear nucleus.</a> J. Comp. Neurol. 518, 4226-4242 (2010).</li><li>Shivdasani, M. N., Mauger, S. J., Rathbone, G. D., Paolini, A. G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Inferior+colliculus+responses+to+multichannel+microstimulation+of+the+ventral+cochlear+nucleus:+Implications+for+auditory+brain+stem+implants.">Inferior colliculus responses to multichannel microstimulation of the ventral cochlear nucleus: Implications for auditory brain stem implants.</a> Journal of Neurophysiology. 99, 1-13 (2007).</li><li>Lenarz, M., Lim, H. H., Patrick, J. F., Anderson, D. J., Lenarz, T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Electrophysiological+Validation+of+a+Human+Prototype+Auditory+Midbrain+Implant+in+a+Guinea+Pig+Model.">Electrophysiological Validation of a Human Prototype Auditory Midbrain Implant in a Guinea Pig Model.</a> JARO. 7, 383-398 (2006).</li><li>Lim, H. H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Auditory+Cortical+Responses+to+Electrical+Stimulation+of+the+Inferior+Colliculus:+Implications+for+an+Auditory+Midbrain+Implant.">Auditory Cortical Responses to Electrical Stimulation of the Inferior Colliculus: Implications for an Auditory Midbrain Implant.</a> Journal of Neurophysiology. 96, 975-988 (2006).</li><li>Otto, K. J., Rousche, P. J., Kipke, D. R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Microstimulation+in+auditory+cortex+provides+a+substrate+for+detailed+behaviors.">Microstimulation in auditory cortex provides a substrate for detailed behaviors.</a> Hearing research. 210, 112-117 (2005).</li><li>Gai, Y. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Detection+of+Tones+in+Reproducible+Noise+Maskers+by+Rabbits+and+Comparison+to+Detection+by+Humans.">Detection of Tones in Reproducible Noise Maskers by Rabbits and Comparison to Detection by Humans.</a> JARO. 8, 522-538 (2007).</li><li>Miller, C. A., Woodruff, K. E., Pfingst, B. E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Functional+responses+from+guinea+pigs+with+cochlear+implants.+I.+Electrophysiological+and+psychophysical+measures.">Functional responses from guinea pigs with cochlear implants. I. Electrophysiological and psychophysical measures.</a> Hearing Research. 92, 85-99 (1995).</li><li>Beitel, R. E., Vollmer, M., Snyder, R. L., Schreiner, C. E., Leake, P. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Behavioral+and+neurophysiological+thresholds+for+electrical+cochlear+stimulation+in+the+deaf+cat.">Behavioral and neurophysiological thresholds for electrical cochlear stimulation in the deaf cat.</a> Audiology &#38; Neurotology. 5, 31-38 (2000).</li><li>Beitel, R. E., Snyder, R. L., Schreiner, C. E., Raggio, M. W., Leake, P. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Electrical+cochlear+stimulation+in+the+deaf+cat:+comparisons+between+psychophysical+and+central+auditory+neuronal+thresholds.">Electrical cochlear stimulation in the deaf cat: comparisons between psychophysical and central auditory neuronal thresholds.</a> J. Neurophysiol. 83, 2145-2162 (2000).</li><li>Vollmer, M., Beitel, R. E., Snyder, 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=Auditory+detection+and+discrimination+in+deaf+cats:+Psychophysical+and+neural+thresholds+for+intracochlear+electrical+signals.">Auditory detection and discrimination in deaf cats: Psychophysical and neural thresholds for intracochlear electrical signals.</a> Journal of Neurophysiology. 86, 2330-2343 (2001).</li><li>LeDoux, J. E., Cicchetti, P., Xagoraris, A., Romanski, L. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+lateral+amygdaloid+nucleus:+sensory+interface+of+the+amygdala+in+fear+conditioning.">The lateral amygdaloid nucleus: sensory interface of the amygdala in fear conditioning.</a> Journal of Neuroscience. 10, 1062-1069 (1990).</li><li>McCreery, D. B., Yuen, T. G., Agnew, W. F., Bullara, L. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+characterization+of+the+effects+on+neuronal+excitability+due+to+prolonged+microstimulation+with+chronically+implanted+microelectrodes.">A characterization of the effects on neuronal excitability due to prolonged microstimulation with chronically implanted microelectrodes.</a> IEEE Transactions on Biomedical Engineering. 44, 931-939 (1997).</li><li>Liu, X., McPhee, G., Seldon, H. L., Clark, G. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Histological+and+physiological+effects+of+the+central+auditory+prosthesis:+surface+versus+penetrating+electrodes.">Histological and physiological effects of the central auditory prosthesis: surface versus penetrating electrodes.</a> Hearing Research. 114, 264-274 (1997).</li><li>Polikov, V. S., Tresco, P. A., Reichert, W. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Response+of+brain+tissue+to+chronically+implanted+neural+electrodes.">Response of brain tissue to chronically implanted neural electrodes.</a> Journal of Neuroscience Methods. 148, 1-18 (2005).</li></ol>

博士アントニオパオリーニは、タッカーデービステクノロジーズとNeuroNexusプローブのオーストラリア代理店のためのオーストラリア代表であるBioengenesis技術Pty Ltdのディレクターです。

テクニックは、このようにデータ処理に必要な研究時間を最小限に抑え、短いトレーニング時間で、急速に差別タスクの範囲をテストし、実質的な自動化を可能にするための手段を提供するここで説明する。移植心電図から得られたデータを、刺激提示のタイミングで心拍数（HR）の変化の計算を自動化することができます使用します。彼らは非常に短い期間のために明らかに心拍数の見かけ上大きな変化を生成し、そのような簡単なエラー検出は、時間のかかる手動のデータのレビューのために要件を最小限に抑えることがECG処理中にエラー（例えば、単一のハートビートの欠落など）を容易に識別することができます。 ECGテレメトリ装置の注入のために説明する手法は一貫してほとんど、あるいは全く干渉の録音を（ 図1＆2を参照）を生成します。しかし、縦隔地域でのリードの配置は比較的小さなバリエーションが近くの筋肉からの干渉につながることができますsおよび特定の呼吸に関連したノイズ。特に場所にリードを縫合した後、注入プロセスの間にリード線の正しい配置を確認し、リード配置の微調整は、干渉を最小限に抑えることができます。 蝸牛神経核への脳移植のプロセスは困難である。バンドパスフィルタをいくつかの周波数範囲のノイズではなく、広帯域ノイズとして、以前に3を使用されているのシリアルプレゼンテーションを使用することにより、電極部位での細胞集団の応答は急速に周波数応答ではなく、以下の固有のノイズの観点から検討することができます応答。周波数同調細胞集団の十分な範囲にアクセスできる場合に迅速に識別する能力は、電気刺激の弁別がテストされている研究において重要である。不十分な周波数分布が得られる場合には、異なる周波数域の刺激間の比較は単純にはできません。それにもかかわらず、長いプロセス周波数 - 振幅応答マッピングの細胞集団のチューニングの広に関する詳細を提供するために重要なままで、代わりに電極を固定する前に実行する必要があります。 行動訓練とテストでは、刺激開始前に試験の間の非刺激（またはサイレント）の期間を含めると、初期刺激の発症への対応を検討することができます。電気的神経刺激を使用する場合は、刺激の発症への応答は、刺激の単純な検出のための証拠を提供しています。したがって、どんな刺激開始応答、2回目の交互刺激が導入された応答が存在しない場合、それは後者のみ刺激を検出することができる推定することができます。このようなサイレント期間を含めることなく、元の刺激が検出されなかったことを決定する方法はありません。 この行動試験法の制限は、フットショックの不在がneuraのプレゼンテーション後に配信することです。音響刺激が提示されたときにLの刺激が恐怖条件で特異性の開発につながる可能性があり、そのような恐怖にのみ発現している。つまり、動物は、神経刺激の特定の感覚の影響が足の衝撃を受けていないに関連付けられていることを学ぶことができます。対照的に、神経刺激の提示後、足の衝撃を提供することは神経の刺激が持つかもしれない音のような特性とは異なる神経刺激自体の恐怖条件につながる可能性があります。神経刺激後のフットショックを除いたときに得られた結果は確かに恐怖条件はアコースティックから神経刺激に一般化されている前者の場合のように、神経刺激後のフットショックを使っている人よりも音のようである神経刺激のための強力な証拠を提供しています。それにもかかわらず、アコースティックではなく、神経刺激に特異性を発症するリスクが存在しています。音響刺激ではなく、純粋なトーンバーストとしてバンドパスフィルタされるノイズを使用し、そのうちの前者開発などの特異性のリスクを減らすことができる優れた、神経刺激の知覚経験を反映するかもしれません。しかし、このような手順では、差別のタスクに影響を与えるフィルタの帯域幅の追加の変数が導入されています。 そのような行動テストのために必要に応じて、任意の慢性的な神経移植に関連付けられた追加の制限は、時間の経過とともに電極または関連する神経組織の機能の変化である。神経組織の刺激は、細胞の損失14と電極への直接の脳組織の応答として、神経活動の13組織変更の一時的な抑制の両方につながることができます15。 注入に説明したアプローチと行動テストは簡単な訓練、試験周波数の制御を行使する能力を音と電気刺激の検出と識別の両方をテストする手段を提供します。 measurとHRの変化を用いる手法恐怖条件付けの電子は、聴覚検査のみならず、しかし、より一般的に刺激を任意の離散期間のために提示することができ、どの感覚で差別の検出が望まれる任意の官能検査にも適用可能である。

<table border="1"><tbody><tr><td> 名 </td><td> 会社 </td><td> モデル </td><td> コメント </td></tr><tr><td> PowerLab </td><td> ADInstruments </td><td> ML880 </td><td>データが移植TR40送信機から受信したレコード</td></tr><tr><td> SmartCtrlコントローラカード</td><td> MEDアソシエイツ</td><td> DIG-716B </td><td>フットショックを含む、行動試験チャンバーを制御</td></tr><tr><td>モジュラー行動試験室</td><td> MEDアソシエイツ</td><td> ENV-009 </td><td>試験室のサイズ：30.5センチメートルX 39.4センチメートル</td></tr><tr><td>嫌悪刺激発生器</td><td> MEDアソシエイツ</td><td> ENV-410B </td><td>ソリッド·ステート·スクランブラーユニットを介してケージの金属バーの床に嫌悪フットショックを提供</td></tr><tr><td>プログラマブル·アッテネータ</td><td> TDT </td><td> PA5 </td><td> AMPLを制御する周波数にわたって安定した振幅を確保するために配信音響信号のitude </td></tr><tr><td>静電スピーカドライバ</td><td> TDT </td><td> ED1 </td><td>静電スピーカー（EC1、ES1）を駆動</td></tr><tr><td>フリーフィールドの静電スピーカー</td><td> TDT </td><td> ES1 </td><td>音は行動試験室にこのスピーカーを使用して表示されます</td></tr><tr><td>結合静電スピーカー</td><td> TDT </td><td> EC1 </td><td>音は、神経インプラント手術中にこのスピーカーを使用して表示されます</td></tr><tr><td>刺激ベースステーション</td><td> TDT </td><td> RX7 </td><td> （MS16と一緒に使用）電気神経刺激の配信を制御</td></tr><tr><td> Microstimulator </td><td> TDT </td><td> MS16 </td><td>マルチチャンネル電気神経刺激を提供します</td></tr><tr><td>加工基地局</td><td> TDT </td><td> RZ2 </td><td>脳の移植時にレコード神経活動を（PZ2プリアンプを使用） </td></tr><tr><td>プリアンプ</td><td> TDT </td><td> PZ2-256 </td><td> 256チャネル、高インピーダンスプリアンプ</td></tr><tr><td>遠隔測定装置の受信機</td><td>テレメトリ研究</td><td> TR162 </td><td> TR40からのデジタル信号を受信し、増幅したアナログ出力に変換</td></tr><tr><td>植込み型心電図遠隔測定装置</td><td>テレメトリ研究</td><td> TR40 </td><td>移植トランスミッタ·デバイス、2kHzのサンプリング</td></tr><tr><td>多機能プロセッサ</td><td>タッカーデービステクノロジーズ（TDT） </td><td> RX6 </td><td>音響刺激を生成するために使用</td></tr><tr><td>頂点Castavaria </td><td>頂点歯科</td><td></td><td>場所に電極を固定するために使用する歯科用アクリル</td></tr><tr><td>クイック·シル接着剤、 低粘度</td><td>世界の精密機器</td><td></td><td>コー​​ト電極シャンクに使用されるシリコンエラストマー</td></tr><tr><td>マルチチャネル電極</td><td> NeuroNexus </td><td> a2x16-10ミリメートル 100-500-413 </td><td> 2シャンク32チャンネル細胞外電極アレイは、注入に使用されます。電極部位は、刺激の準備のために酸化イリジウムのコーティングを生成するためにアクティブ化されています。 </td></tr></tbody></table>

behavioral determination of stimulus pair discrimination of auditory acoustic and electrical stimuli using a classical conditioning and heart-rate approach

急性動物製剤は前向きにそのような聴性脳幹インプラント1-3と聴覚中脳インプラント4,5のような神経聴覚義肢に電極の設計と統合のための刺激技術を調査研究に使用されている。急性実験では、インプラントの有効性に最初の洞察力を与えることができますが、慢性的に移植し、覚醒動物をテストすることは感覚の心理物理学的特性を調べることの利点は、移植デバイスの6,7を使用して誘導しています。 そのような報酬ベースのオペラント条件6-8、条件回避9-11、または古典的な恐怖条件付け12などのいくつかの技術は、関連する刺激属性の検出の行動確認を提供するために使用されている。技術の選択は、時間効率（多くの場合、貧しい報酬ベースのアプローチ）で、複数のテストをする機能など、バランスの側面が含まれます刺激（条件回避に限る。）同時に属性、繰り返し刺激（生理的な措置が採用されている潜在的な制約）の尺度の信頼性。 ここでは、古典的な恐怖条件付け行動の方法は、同時に刺激の検出、および2つの刺激の間に差別の両方をテストするために使用されるかもしれない提示されます。心拍数は、凍結の動作や他のそのような対策のためのコーディング時間のかかるビデオの必要性を低減または排除する恐怖反応の指標として使用されます（そのような措置が収束の証拠を提供するために含まれている可能性がありますが）。動物はそれぞれ48刺激試験を提供し、3つの2時間のコンディショニングセッションでこれらの技術を使用して調整した。その後の48試行のテストセッションは、その後提示ペアで各刺激の検出、および各ペアのメンバーの刺激の間にテストの弁別をテストするために使用されました。 この行動のメソッドは、で表示されます聴覚補綴研究におけるその活用のコンテキスト。心電図テレメトリ装置の注入が表示されます。慢性的な使用のための所定の位置に音響刺激に対する神経応答のモニタリングによって導か蝸牛神経核、および電極の固定に脳電極のそれ以降の注入は、同様に表示されます。

Watch this Scientific Journal Video about Behavioral Determination of Stimulus Pair Discrimination of Auditory Acoustic and Electrical Stimuli Using a Classical Conditioning and Heart-rate Approach at

Behavioral Determination of Stimulus Pair Discrimination of Auditory Acoustic and Electrical Stimuli Using a Classical Conditioning and Heart-rate Approach

ラットの聴覚補綴研究のための古典的な恐怖条件付け行動パラダイムのアプリケーションが記述されています。このパラダイムは、検出、およびアウトカム指標として心拍数を使用して別個の音響および電気刺激の間の差別の両方を識別するためのメカニズムを提供します。

古典的条件とハートレート·アプローチを用いた聴覚の音響および電気刺激の刺激ペアの差別の行動決定

Acute animal preparations have been used in research prospectively investigating electrode designs and stimulation techniques for integration into neural ...

behavioral-determination-stimulus-pair-discrimination-auditory

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14.4K ビュー.  La Trobe University. ラットの聴覚補綴研究のための古典的な恐怖条件付け行動パラダイムのアプリケーションが記述されています。このパラダイムは、検出、およびアウトカム指標として心拍数を使用して別個の音響および電気刺激の間の差別の両方を識別するためのメカニズムを提供します。

ビデオ: Behavioral Determination of Stimulus Pair Discrimination of Auditory Acoustic and Electrical Stimuli Using a Classical Conditioning and Heart-rate Approach

Behavioural Pharmacology in Classical Conditioning of the Proboscis Extension Response in Honeybees (Apis mellifera)

Honeybees (Apis mellifera) are well known for their communication and orientation skills and for their impressive learning capability1,2. Because the survival of a honeybee colony depends on the exploitation of food sources, forager bees learn and memorize variable flower sites as well as their profitability. Forager bees can be easily trained in natural settings where they forage at a feeding site and learn the related signals such as odor or color. Appetitive associative learning can also be studied under controlled conditions in the laboratory by conditioning the proboscis extension response (PER) of individually harnessed honeybees3,4. This learning paradigm enables the study of the neuronal and molecular mechanisms that underlie learning and memory formation in a simple and highly reliable way5-12. A behavioral pharmacology approach is used to study molecular mechanisms. Drugs are injected systemically to interfere with the function of specific molecules during or after learning and memory formation13-16.
Here we demonstrate how to train harnessed honeybees in PER conditioning and how to apply drugs systemically by injection into the bee flight muscle.

Behavioural Pharmacology in Classical Conditioning of the Proboscis Extension Response in Honeybees Apis mellifera

We demonstrate how to implement a behavioral pharmacology method in an appetitive olfactory conditioning paradigm in honeybees (Apis mellifera) by systemic application of drugs. This method allows investigation of the mechanisms underlying learning and memory formation in a simple and reliable way.

ミツバチのテングザルの拡張レスポンスの古典的条件における行動薬理学（セイヨウミツバチ）

Honeybees (Apis mellifera) are well known for their communication and orientation skills and for their impressive learning capability1,2. Because the ...

神経科学

A Lightweight, Headphones-based System for Manipulating Auditory Feedback in Songbirds

Experimental manipulations of sensory feedback during complex behavior have provided valuable insights into the computations underlying motor control and sensorimotor plasticity1. Consistent sensory perturbations result in compensatory changes in motor output, reflecting changes in feedforward motor control that reduce the experienced feedback error. By quantifying how different sensory feedback errors affect human behavior, prior studies have explored how visual signals are used to recalibrate arm movements2,3 and auditory feedback is used to modify speech production4-7. The strength of this approach rests on the ability to mimic naturalistic errors in behavior, allowing the experimenter to observe how experienced errors in production are used to recalibrate motor output.
Songbirds provide an excellent animal model for investigating the neural basis of sensorimotor control and plasticity8,9. The songbird brain provides a well-defined circuit in which the areas necessary for song learning are spatially separated from those required for song production, and neural recording and lesion studies have made significant advances in understanding how different brain areas contribute to vocal behavior9-12. However, the lack of a naturalistic error-correction paradigm - in which a known acoustic parameter is perturbed by the experimenter and then corrected by the songbird - has made it difficult to understand the computations underlying vocal learning or how different elements of the neural circuit contribute to the correction of vocal errors13.
The technique described here gives the experimenter precise control over auditory feedback errors in singing birds, allowing the introduction of arbitrary sensory errors that can be used to drive vocal learning. Online sound-processing equipment is used to introduce a known perturbation to the acoustics of song, and a miniaturized headphones apparatus is used to replace a songbird's natural auditory feedback with the perturbed signal in real time. We have used this paradigm to perturb the fundamental frequency (pitch) of auditory feedback in adult songbirds, providing the first demonstration that adult birds maintain vocal performance using error correction14. The present protocol can be used to implement a wide range of sensory feedback perturbations (including but not limited to pitch shifts) to investigate the computational and neurophysiological basis of vocal learning.

We describe the design and assembly of miniaturized headphones suitable for replacing a songbird&#x2019;s natural auditory feedback with a manipulated acoustic signal. Online sound processing hardware is used to manipulate song output, introduce real-time errors in auditory feedback via the headphones, and drive vocal motor learning.

鳴禽類には聴覚フィードバックを操作するための軽量、ヘッドフォンベースのシステム

Experimental manipulations of sensory feedback during complex behavior have provided valuable insights into the computations underlying motor control and ...

Functional Imaging of Auditory Cortex in Adult Cats using High-field fMRI

Current knowledge of sensory processing in the mammalian auditory system is mainly derived from electrophysiological studies in a variety of animal models, including monkeys, ferrets, bats, rodents, and cats. In order to draw suitable parallels between human and animal models of auditory function, it is important to establish a bridge between human functional imaging studies and animal electrophysiological studies. Functional magnetic resonance imaging (fMRI) is an established, minimally invasive method of measuring broad patterns of hemodynamic activity across different regions of the cerebral cortex. This technique is widely used to probe sensory function in the human brain, is a useful tool in linking studies of auditory processing in both humans and animals and has been successfully used to investigate auditory function in monkeys and rodents. The following protocol describes an experimental procedure for investigating auditory function in anesthetized adult cats by measuring stimulus-evoked hemodynamic changes in auditory cortex using fMRI. This method facilitates comparison of the hemodynamic responses across different models of auditory function thus leading to a better understanding of species-independent features of the mammalian auditory cortex.

Functional studies of the auditory system in mammals have traditionally been conducted using spatially-focused techniques such as electrophysiological recordings. The following protocol describes a method of visualizing large-scale patterns of evoked hemodynamic activity in the cat auditory cortex using functional magnetic resonance imaging.

ハイフィールドのfMRIを使って大人の猫における聴覚皮質の機能イメージング

Current knowledge of sensory processing in the mammalian auditory system is mainly derived from electrophysiological studies in a variety of animal ...

High Resolution Quantitative Synaptic Proteome Profiling of Mouse Brain Regions After Auditory Discrimination Learning

The molecular synaptic mechanisms underlying auditory learning and memory remain largely unknown. Here, the workflow of a proteomic study on auditory discrimination learning in mice is described. In this learning paradigm, mice are trained in a shuttle box Go/NoGo-task to discriminate between rising and falling frequency-modulated tones in order to avoid a mild electric foot-shock. The protocol involves the enrichment of synaptosomes from four brain areas, namely the auditory cortex, frontal cortex, hippocampus, and striatum, at different stages of training. Synaptic protein expression patterns obtained from trained mice are compared to na&#239;ve controls using a proteomic approach. To achieve sufficient analytical depth, samples are fractionated in three different ways prior to mass spectrometry, namely 1D SDS-PAGE/in-gel digestion, in-solution digestion and phospho-peptide enrichment. 
High-resolution proteomic analysis on a mass spectrometer and label-free quantification are used to examine synaptic protein profiles in phospho-peptide-depleted and phospho-peptide-enriched fractions of synaptosomal protein samples. A commercial software package is utilized to reveal proteins and phospho-peptides with significantly regulated relative synaptic abundance levels (trained/na&#239;ve controls). Common and differential regulation modes for the synaptic proteome in the investigated brain regions of mice after training were observed. Subsequently, meta-analyses utilizing several databases are employed to identify underlying cellular functions and biological pathways.

The identification of molecules and pathways controlling synaptic plasticity and memory is still a major challenge in neuroscience. Here, a workflow is described addressing the relative quantification of synaptic proteins supposedly involved in the molecular reorganization of synapses during learning and memory consolidation in an auditory learning paradigm.

聴覚弁別学習した後、マウス脳領域の高分解能定量的シナプスプロテオームプロファイリング

The molecular synaptic mechanisms underlying auditory learning and memory remain largely unknown. Here, the workflow of a proteomic study on auditory ...

The Use of Trace Eyeblink Classical Conditioning to Assess Hippocampal Dysfunction in a Rat Model of Fetal Alcohol Spectrum Disorders

Neonatal rats were administered a relatively high concentration of ethyl alcohol (11.9% v/v) during postnatal days 4-9, a time when the fetal brain undergoes rapid organizational change and is similar to accelerated brain changes that occur during the third trimester in humans. This model of fetal alcohol spectrum disorders (FASDs) produces severe brain damage, mimicking the amount and pattern of binge-drinking that occurs in some pregnant alcoholic mothers. We describe the use of trace eyeblink classical conditioning (ECC), a higher-order variant of associative learning, to assess long-term hippocampal dysfunction that is typically seen in alcohol-exposed adult offspring. At 90 days of age, rodents were surgically prepared with recording and stimulating electrodes, which measured electromyographic (EMG) blink activity from the left eyelid muscle and delivered mild shock posterior to the left eye, respectively. After a 5 day recovery period, they underwent 6 sessions of trace ECC to determine associative learning differences between alcohol-exposed and control rats. Trace ECC is one of many possible ECC procedures that can be easily modified using the same equipment and software, so that different neural systems can be assessed. ECC procedures in general, can be used as diagnostic tools for detecting neural pathology in different brain systems and different conditions that insult the brain.

Trace eyeblink classical conditioning (ECC) was used to assess hippocampal-dependent associative learning in adult rats that were administered a high concentration (11.9% v/v) of alcohol during early neonatal brain development. In general, ECC procedures are sound diagnostic tools for detecting brain dysfunction across many psychological and biomedical settings.

胎児アルコール スペクトルの無秩序のモデルラットにおける海馬機能障害を評価するためにトレース瞬目反射条件づけの使用

Neonatal rats were administered a relatively high concentration of ethyl alcohol (11.9% v/v) during postnatal days 4-9, a time when the fetal brain ...

Drosophila Courtship Conditioning As a Measure of Learning and Memory

Many insights into the molecular mechanisms underlying learning and memory have been elucidated through the use of simple behavioral assays in model organisms such as the fruit fly, Drosophila melanogaster. Drosophila is useful for understanding the basic neurobiology underlying cognitive deficits resulting from mutations in genes associated with human cognitive disorders, such as intellectual disability (ID) and autism. This work describes a methodology for testing learning and memory using a classic paradigm in Drosophila known as courtship conditioning. Male flies court females using a distinct pattern of easily recognizable behaviors. Premated females are not receptive to mating and will reject the male&#39;s copulation attempts. In response to this rejection, male flies reduce their courtship behavior. This learned reduction in courtship behavior is measured over time, serving as an indicator of learning and memory. The basic numerical output of this assay is the courtship index (CI), which is defined as the percentage of time that a male spends courting during a 10 min interval. The learning index (LI) is the relative reduction of CI in flies that have been exposed to a premated female compared to na&#239;ve flies with no previous social encounters. For the statistical comparison of LIs between genotypes, a randomization test with bootstrapping is used. To illustrate how the assay can be used to address the role of a gene relating to learning and memory, the pan-neuronal knockdown of Dihydroxyacetone phosphate acyltransferase (Dhap-at) was characterized here. The human ortholog of Dhap-at, glyceronephosphate O-acyltransferase (GNPT), is involved in rhizomelic chondrodysplasia punctata type 2, an autosomal-recessive syndrome characterized by severe ID. Using the courtship conditioning assay, it was determined that Dhap-at is required for long-term memory, but not for short-term memory. This result serves as a basis for further investigation of the underlying molecular mechanisms.

Drosophila Courtship Conditioning As a Measure of Learning and Memory

This protocol describes a Drosophila learning and memory assay called courtship conditioning. This classic assay is based on a reduction of male courtship behavior after sexual rejection by a non-receptive premated female. This natural form of behavioral plasticity can be used to test learning, short-term memory, and long-term memory.

ショウジョウバエの訓練と記憶の尺度としてのコンディショニング

Many insights into the molecular mechanisms underlying learning and memory have been elucidated through the use of simple behavioral assays in model ...

Quantifying Infra-slow Dynamics of Spectral Power and Heart Rate in Sleeping Mice

Three vigilance states dominate mammalian life: wakefulness, non-rapid eye movement (non-REM) sleep, and REM sleep. As more neural correlates of behavior are identified in freely moving animals, this three-fold subdivision becomes too simplistic. During wakefulness, ensembles of global and local cortical activities, together with peripheral parameters such as pupillary diameter and sympathovagal balance, define various degrees of arousal. It remains unclear the extent to which sleep also forms a continuum of brain states-within which the degree of resilience to sensory stimuli and arousability, and perhaps other sleep functions, vary gradually-and how peripheral physiological states co-vary. Research advancing the methods to monitor multiple parameters during sleep, as well as attributing to constellations of these functional attributes, is central to refining our understanding of sleep as a multifunctional process during which many beneficial effects must be executed. Identifying novel parameters characterizing sleep states will open opportunities for novel diagnostic avenues in sleep disorders.
We present a procedure to describe dynamic variations of mouse non-REM sleep states via the combined monitoring and analysis of electroencephalogram (EEG)/electrocorticogram (ECoG), electromyogram (EMG), and electrocardiogram (ECG) signals using standard polysomnographic recording techniques. Using this approach, we found that mouse non-REM sleep is organized into cycles of coordinated neural and cardiac oscillations that generate successive 25-s intervals of high and low fragility to external stimuli. Therefore, central and autonomic nervous systems are coordinated to form behaviorally distinct sleep states during consolidated non-REM sleep. We present surgical manipulations for polysomnographic (i.e., EEG/EMG combined with ECG) monitoring to track these cycles in the freely sleeping mouse, the analysis to quantify their dynamics, and the acoustic stimulation protocols to assess their role in the likelihood of waking up. Our approach has already been extended to human sleep and promises to unravel common organizing principles of non-REM sleep states in mammals.

Here, we present experimental and analytical procedures to describe the temporal dynamics of the neural and cardiac variables of non-REM sleep in mice, which modulate sleep responsiveness to acoustic stimuli.

睡眠中のマウスにおけるスペクトルパワーおよび心拍数の低速ダイナミクスの定量化

Three vigilance states dominate mammalian life: wakefulness, non-rapid eye movement (non-REM) sleep, and REM sleep. As more neural correlates of behavior ...

Desensitization and Recovery of Crayfish Photoreceptors Upon Delivery of a Light Stimulus

A method to study desensitization and recovery of crayfish photoreceptors is presented. We performed intracellular electrical recordings of photoreceptor cells in isolated eyestalks using the discontinuous single electrode-switched voltage-clamp configuration. First, with a razor blade we made an opening in the dorsal cornea to get access to the retina. Thereafter, we inserted a glass electrode through the opening, and penetrated a cell as reported by the recording of a negative potential. Membrane potential was clamped at the photoreceptor's resting potential and a light-pulse was applied to activate currents. Finally, the two light-flash protocol was employed to measure current desensitization and recovery. The first light-flash triggers, after a lag period, the transduction ionic current, which after reaching a peak amplitude decays towards a desensitized state; the second flash, applied at varying time intervals, assesses the state of the light-activated conductance. To characterize the light-elicited current, three parameters were measured: 1) latency (the time elapsed between light flash delivery and the moment in which current achieves 10% of its maximum value); 2) peak current; and 3) desensitization time constant (exponential time constant of the current decay phase). All parameters are affected by the first pulse.
To quantify recovery from desensitization, the ratio p2/p1 was employed versus time between pulses. p1 is the peak current evoked by the first light-pulse, and p2 is the peak current evoked by the second pulse. These data were fitted to a sum of exponential functions. Finally, these measurements were carried out as function of circadian time.

A protocol for the study of desensitization and sensitivity recovery of crayfish photoreceptors as a function of circadian time is presented.

光刺激の送達時のザリガニ光受容体の脱感作と回復

A method to study desensitization and recovery of crayfish photoreceptors is presented. We performed intracellular electrical recordings of photoreceptor ...

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 ...

Cochlear Implant Surgery and Electrically-evoked Auditory Brainstem Response Recordings in C57BL/6 Mice

Cochlear implants (CIs) are neuroprosthetic devices that can provide a sense of hearing to deaf people. However, a CI cannot restore all aspects of hearing. Improvement of the implant technology is needed if CI users are to perceive music and perform in more natural environments, such as hearing out a voice with competing talkers, reflections, and other sounds. Such improvement requires experimental animals to better understand the mechanisms of electric stimulation in the cochlea and its responses in the whole auditory system. The mouse is an increasingly attractive model due to the many genetic models available. However, the limited use of this species as a CI model is mainly due to the difficulty of implanting small electrode arrays. More details about the surgical procedure are therefore of great interest to expand the use of mice in CI research.
In this report, we describe in detail the protocol for acute deafening and cochlear implantation of an electrode array in the C57BL/6 mouse strain. We demonstrate the functional efficacy of this procedure with electrically-evoked auditory brainstem response (eABR) and show examples of facial nerve stimulation. Finally, we also discuss the importance of including a deafening procedure when using a normally hearing animal. This mouse model provides a powerful opportunity to study genetic and neurobiological mechanisms that would be of relevance for CI users.

Animal models of cochlear implants can advance knowledge of the technological bases of treating permanent sensorineural hearing loss with electrical stimulation. This study presents a surgical protocol for acute deafening and cochlear implantation of an electrode array in mice as well as the functional assessment with auditory brainstem response.

人工内耳手術と c57bl/6 マウスに電気的誘発脳幹の応答録音

Cochlear implants (CIs) are neuroprosthetic devices that can provide a sense of hearing to deaf people. However, a CI cannot restore all aspects of ...