이 프로젝트는 NIH 교부금 DA19112 (DGW)와 DA026994 (CMO)에 의해 지원되었다. 일러스트 레이션은 캐서린 Louderback에 의해 제공되었다. 실험은 밴더빌트 Murine Neurobehavioral 연구실에서 수행되었다.

1. reinforcer로 다양한 시각과 청각 자극을 사용하여 operant 테스트 세션을 실행하는 프로그램을 작성 <ol><li> 고정 비율 (FR) 세션 : 주택 조명 및 팬 세션 동안 켜져와 길이 세션을 한 시간을 확인하십시오. 진보 비율 세션, 세션 이시간 길이합니다. 양쪽 레버는 레버가 동물 (각 동물에 대한 레버 할당 전혀 변경)를 통해 &quot;활성&quot;대 &quot;비활성&quot;지정 세션과 보상 기간 연장했습니다. </li><li> 각 reinforcer은 다음 매개 변수에 따라 다양합니다 그러한 방식으로 프로그램을 코드 : <ul><li> 2, 4, 6, 또는 8 초 : 각 r​​einforcer 무작위로 선택한 다음 서비스 기간이 중 하나입니다. </li><li> 50 % 듀티 사이클과 0.625, 1.25, 2.5, 또는 5 Hz에서 각 각 reinforcer 무작위로 선택한 다음 자극 램프 플래시 요금 중 하나입니다. </li><li> 각 자극 램프 플래시가 왼쪽 또는 챔버의 오른쪽 하나를 임의로 있습니다. </li><li> reinforcer 기간 동안 청각 자극을 제공, 우리 연구실에, 우리는 챔버의 배경 소음 사운드 위에 약 3dB를 제공하는 주입 펌프를 실행. </li></ul></li><li> 1 : 실시간으로 다음과 같은 값을 표시하는 프로그램을 코드입니다. 활성 레버 프레스, 2의 개수입니다. 비활성 레버 프레스 3의 개수입니다. reinforcers 4의 개수입니다. 시간 (0.1 초 단위). </li></ol> 2. 동물 (3 일 과정)를 처리할 <ol><li> 동물 시설에 acclimation 후 동물을 처리 시작합니다. 이것은 뭔가를 집어 들어서 이송될 수있는 동물을 길들 것입니다. </li><li> 케이지에 장갑 낀 손을 넣어하고 90 초위한 앉아셔서하여 시작하십시오. 모든 마우스가 그 시간에 손을 조사하지 않은 경우 부드럽게 쥐를 향해 손을 이동하고 각 냄새를 맡고 및 / 또는 진행하기 전에 손을 연락을 기다립니다. </li><li> 조심스럽게 꼬리의 기반 한 각 마우스 하나를 선택하여 손에 배치, 신속하게 그것을 올려서와 마우스가 케이지에 다시 손을의에서 도보 수 있도록 다시 아래로 그것을 가져올 수있을 것이다. </li><li> 마우스의 행동에 따라 각각의 마우스를 50-10 회 반복합니다. 이것이 완료 최종 시간, 날짜에 따라 일정 기간 동안 (이것은 당신의 손에 서)를 마우스 높은시오. 1 일 : 5 초, 일 2 : 10 초, 3 일 : 15 초. 각 마우스 그날이 기준을 충족하는지 확인하십시오. 1 일에, 새장 사이에 장갑을 변경합니다. </li><li> 마우스가 손에있는 동안 주 2 스트로크 동물의 뒷면에 시작. 또한 2 일, 매일 동물을 무게 시작합니다. 제목 번호를 나타내는 수있는 샤피 각 동물의 꼬리를 표시합니다. </li><li> 주사는 실험 기간 동안 제공됩니다면, 주 2 주사로 쥐 habituating 시작합니다. 새장의 모든 마우스 처리와 하루 기준을 충족 후에이 완료되어야합니다. </li></ol> 3. 클린 및 테스트 장비 <ol><li> 온수 바닥 냄비를 씻으십시오. </li><li> 30 % 에탄올로 operant 챔버 벽 및 바닥 청소. </li><li> , 주택 조명, 팬, 그리고 자극 조명 켜지 레버를 확장하고, 기록 레버 프레스 테스트 프로그램을 실행합니다. </li><li> 모든 조명과 팬들이 제대로 작동하는지 확인하고 모든 레버 프레스가 기록되는 것을 보장하기 위해 프로그램을 테스트합니다. </li><li> 30 % 에탄올로 청소 레버스. </li></ol> 4. operant 세션 (세션은 하루 중 같은 시간에 5-6일 / 주한다)를 수행 <ol><li> 각 마우스의 무게를. </li><li> 각각의 챔버로 프로그램을로드하고 적절하게 실험을 주석. 활성 레버는 동물 (즉, 활성 레버가 생쥐의 절반은 왼쪽 레버에 할당되며 오른쪽 레버는 다른 반쪽에 대한 활성) 사이 counterbalanced해야하지만, 마우스 마우스가되면 활성 레버 사이드 변경 절대 할당. </li><li> 그 지정된 챔버 각 마우스를 전송 챔버를 닫고하고, 세션을 시작합니다. </li><li> 세션이 끝나면 즉시 마우스를 제거하고 꼬리를 다시 표시합니다. </li><li> 클린 챔버 스는 제 3의 설명. </li><li> 활성 및 비활성 레버 프레스의 개수에 대한 데이터를 분석합니다. reinforcers 및 / 또는 레버 정밀도 (% 활성 레버 프레스)의 개수도보고 있습니다. 생쥐는 OSS에 대한 치료의 효과에 대한 검사가 될 경우, 테스트하는 모든 마우스 (예 : 인수 기준을 충족했는지 확인&gt; 마지막 3 FR - 1 세션 20 활성 레버 프레스 및&gt; 65% 활성 레버 프레스 ) 전에 치료를 시작합니다. </li><li> 취득 후 FR - 1 강화의 일정은 (예를 들어, 높은 고정 비율, 진보적인 비율, 임의의 비율 등)을 변경할 수 있습니다, 응답. </li></ol> 5. 대표 결과 남성 C57Bl/6J 마우스로 OSS 수집의 예제는 그림 1 (23 복제)에 표시됩니다. 컨트롤 마우스는 동일한 조건을 받았습니다 중 레버 그 레버 프레스를 제외하고 아무 conse 없었다quence. 생쥐의 다른 일대는 그림 2에 표시됩니다. 다른 그룹은 식품 보강을받은 반면 본 실험에서는 생쥐 한 그룹은 OSS 보강을 받았습니다. 우리는 식품 광고 libitum 액세스 조건 하에서 응답을 모두 고정하고 진취적인 비율은 OSS와 (그림 2, A와 B) 확인 10 % 응답 사이의 유사 것으로 나타났습니다. 이것은 기아 상태 또는 반응 속도의 차이로 인한 잠재적인 confounds를 피할 두 가지 보강 유형 (감각 및 식품)에 대한 조작의 효과 비교를위한 수 있습니다. <img src="/files/ftp_upload/2292/2292fig1.jpg" alt="그림 1" /> 그림 1 :. OSS의 마우스 및 제어에 의해 레버 프레스 비활성 레버 프레스 아무런 결과도 없었하면서 OSS 마우스는 각 활성 레버 프레스 (강화의 FR - 1 일정) 다음과 같은 다양한 시각과 청각 자극을 받았습니다. 컨트롤 마우스는 동일한 조건을 받았습니다하지만, 어느 레버를 (레버은 활성 및 비활성 레버가 OSS의 마우스에 대한 counterbalanced되는 동일한 방식으로 동물에 걸쳐 1과 2를 표시된하고 counterbalanced 있습니다) 누르면 아무런 결과가 없었다. OSS 마우스로 눌러 활성 레버가 눌러 비활성 레버에 상대적으로 증가되었다 (* P &lt;0.05, ** P &lt;0.01)와 컨트롤 키를 눌러 아닌 철근 레버로 (N = 7 8, $ P &lt;0.05, $ $ P &lt;0.01 ). 23 재현 그림. <img src="/files/ftp_upload/2292/2292fig2.jpg" alt="그림 2" /> 그림 2. 음식에 대한 응답 OSS의 마우스 및 마우스에 의해 레버 프레스 A.) 마우스는 OSS의 자극이나 음식 reinforcer (10 % 보장)에 대한 강화의 FR - 1 일정에 응답했습니다. 모든 생쥐는 실험 기간 동안 식품 광고 libidum 액세스를했다. B.)는 FR - 1 세션 후, 생쥐는 5 일 동안 강화의 진보적인 비율 (PR) 일정을 고급되었습니다. 데이터는 일 사 각 동물하기위한 다섯 가지의 값의 의미를 나타냅니다. 완료 최종 비율은 Y 축 오른쪽에보고하고 해당 reinforcer (예 : 30 응답는 이전에 다음 ID로 구 reinforcers를 취득한 후 10 번째 reinforcer를 얻을 필요합니다)을 구하는 데 필요한 응답의 수를 의미합니다.

<ol>
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C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Multivariate+analyses+reveal+common+and+drug-specific+genetic+influences+on+responses+to+four+drugs+of+abuse.">Multivariate analyses reveal common and drug-specific genetic influences on responses to four drugs of abuse.</a> Trends Pharmacol Sci. 29, 537-543 (2008).</li><li>Mozhui, K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Strain+differences+in+stress+responsivity+are+associated+with+divergent+amygdala+gene+expression+and+glutamate-mediated+neuronal+excitability.">Strain differences in stress responsivity are associated with divergent amygdala gene expression and glutamate-mediated neuronal excitability.</a> J Neurosci. 30, 5357-5367 (2010).</li><li>Hefner, K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Impaired+fear+extinction+learning+and+cortico-amygdala+circuit+abnormalities+in+a+common+genetic+mouse+strain.">Impaired fear extinction learning and cortico-amygdala circuit abnormalities in a common genetic mouse strain.</a> J Neurosci. 28, 8074-8085 (2008).</li><li>Elmer, G. I., Pieper, J. O., Hamilton, L. R., Wise, R. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Qualitative+differences+between+C57BL/6J+and+DBA/2J+mice+in+morphine+potentiation+of+brain+stimulation+reward+and+intravenous+self-administration.">Qualitative differences between C57BL/6J and DBA/2J mice in morphine potentiation of brain stimulation reward and intravenous self-administration.</a> Psychopharmacology (Berl). 208, 309-321 (2010).</li></ol>

관심 없음 충돌 선언하지 않습니다.

원하는 Operant 감각은 마우스가 선택의 동물이다 정맥 주사 약물 자기 관리에 유용한 대안입니다. 수술이나 카테터 유지도가 필요하다는 사실은 이것이 마우스에서 중요한 기술적 장애물 있으므로, 유리한 것입니다. 이 같은 음식 등 다른 자연 reinforcers와는 강화의 측면을 측정하는 수 있기 때문에 OSS도 매력적입니다. 이것은 마우스의 행동 조치가 다른 환경 조건 24에</sup...

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		<th>Material Name</th>
		<th>Type</th>
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		<th>Catalogue Number</th>
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<td>Drug self-administration test package for mouse: extra-wide chamber and retractable levers</td>
<td>&nbsp;</td>
<td><a href="http://www.med-associates.com/">Med Associates, Inc</a></td>
<td>MED-307W-CT-D1</td>
<td>Levers are ultra-sensitive (require ~2 grams force) and are mounted 2.2 cm above the floor. Yellow stimulus lamps are mounted 2 cm above each lever.</td>
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<tr>
<td>Interface and software package</td>
<td>&nbsp;</td>
<td><a href="http://www.med-associates.com/">Med Associates, Inc</a></td>
<td>MED-SYST-16</td>
<td>This is the package for up to 16 chambers.</td>
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operant sensation seeking in the mouse

Operant 방법은 동기를 행동의 연구를위한 강력한 행동 도구입니다. 이러한 &#39;자기 관리&#39;방식은 높은 건설의 타당성에 의한 약물 중독 연구에 광범위하게 사용되었습니다. Operant 연구는 연구자에게 중독 과정의 여러 측면의 잠복기 조사를위한 도구를 제공합니다. 예를 들어, 급성 보강 (약물과 비 약물 모두)의 메커니즘은 자기 관리 행동 1-6 영향을 분자 표적의 능력을 결정하는 약리 또는 유전 도구를 사용하여 테스트하실 수 있습니다. 또한, 약물 또는 음식을 추구하는 행동은 기본 reinforcer의 부재에서 공부하고,이 과정을 방해하는 약리 물질의 능력은 중독 3의 치료에 유용할 수 있습니다 분자 표적과 화합물의 발견 잠복기 모델입니다 수 있습니다 7-9. 마우스에 정맥 주사 약물 자기 관리 연구를 수행하는 하나의 문제가 카테 테르의 명백을 유지의 기술적인 어려움이다. 이 실험에서 마찰 속도가 높다 40 % 또는 10-15 이상에 도달할 수 있습니다. 약물 자기 관리와 함께 또 다른 일반적인 문제는 reinforcer의 pharmacologically 유발 효과가 특정 동작을 생산하는 통찰력이다. 예를 들어, 강화 및 psychostimulants의 신경 효과 측정들은 psychomotor 효과에 의해 실마리를 못찾고 수 있습니다. 약물 중독을 공부 그들의 유틸리티가 마약 자기 관리를 변경 일부 조작 음식 자기 관리에 미치는 영향을 최소화있다는 사실에 의해 제한되지만 식품 보강을 사용 Operant 방법은 이러한 함정을 피할 수 있습니다. 예를 들어, D1의 도파민 수용체의 mesolimbic 도파민의 병변이나 한방 음식 자체 관리 12,16에 큰 영향을하지 않고 코카인 자기 관리를 줄일 수 있습니다. 감각 자극은 기본 reinforcers (예 : 에어컨하지 reinforcers) 17-22로 응답 operant 지원 능력에 대해 설명했습니다. 청각 및 시각 자극은 자기 관리 놀라울 정도로 작은이 보강 기본 신경 메커니즘에 대해 알고 있지만, 여러 종류 18,21,23로. (OSS) 모델을 추구 operant 센세이션이 감각 강화 24 신경 메커니즘의 연구가 중요 있도록 마우스의 감각 자기 관리를위한 강력한 모델입니다. OSS의 추가 장점은 중독과 관련이있을 수 있습니다 operant 행동의 차이에 대한 돌연변이 쥐를 화면에있는 능력입니다. 우리는 이전에 psychostimulant 자기 관리의 결함으로 표시 도파민 D1 수용체 녹아웃 마우스는, 또한 OSS 24를 얻기 실패보고있다. 이것은 이들 쥐가 음식 reinforcer로 사용하는 경우 operant 작업을 학습 할 수있다의 독특한 찾는 것입니다. 식품 보강을 사용 operant 연구는 일반 동기 행동과 위에서 언급한 메커니즘을 기본 식품 강화, 연구에 유용하게 사용될 수 있지만 이러한 연구는 약물 중독의 분자 메커니즘을 연구하기 위해 응용 프로그램에 제한됩니다. 따라서, OSS 약물 중독 프로세스의 연구에 특히 매력적인 모델이되도록 식품 강화에서 구분되는 감각과 psychostimulant 보강을 중재 유사한 신경 기판이있을 수 있습니다. OSS 및 약물 reinforcers의 다른 분자 표적 사이의 중복의 정도는 불분명하지만, 우리가 현재 추구하는 주제이다. 이러한 멸종에 대한 저항과 같은 중독의 일부 측면은 OSS와 관찰 수 있지만, 우리는 상승 25이 모델 24 관찰하고 있지 않은 것으로 나타났습니다. 흥미롭게도, 섭취량 및 중독의 다른 측면의 상승은 자당 26 자기 관리와 관찰됩니다. 따라서 비 약물 operant 절차 중독과 관련된 프로세스를 연구하기 위해 원하는 때, 음식이나 감각 reinforcers이 가장 요구되는 특정 질문에 맞게 선택할 수 있습니다. 결론적으로, 음식 자체 관리 및 마우스의 OSS 모두 높은 처리량 동기 부여에 관련된 신경 타겟의 약리 또는 유전자 조작의 효과를 연구하기 위해 의미있게 정맥 ​​카테터를 필요하지 않는 장점이 있습니다. reinforcer로 음식을 사용하는 operant 테스트는 음식 섭취의 규제에 관한 연구에 특히 유용하지만, OSS는 감각 자극의 강화 메커니즘을 연구하고 특히 APT하고 추구 참신하고 중독에 광범위한 적용가있을 수 있습니다.

Watch this Scientific Journal Video about Operant Sensation Seeking in the Mouse at JoVE.com

Operant Sensation Seeking in the Mouse

이 프로토콜에서는 마우스의 reinforcer으로 감각 자극을 사용하여 operant 학습하는 방법을 설명합니다. 이것은 사전에 훈련이나 음식 제한을 필요로하지 않으며 그것은 같은 음식으로 약리 또는 자연 reinforcer를 사용하지 않고 동기 행동의 연구를 수 있습니다.

마우스의 추구 Operant 감각

Operant methods are powerful behavioral tools for the study of motivated behavior.  These 'self-administration' methods have been used extensively in drug ...

Research

JoVE Journal

Neuroscience

12.9K 조회수.  Vanderbilt University Medical Center. 이 프로토콜에서는 마우스의 reinforcer으로 감각 자극을 사용하여 operant 학습하는 방법을 설명합니다. 이것은 사전에 훈련이나 음식 제한을 필요로하지 않으며 그것은 같은 음식으로 약리 또는 자연 reinforcer를 사용하지 않고 동기 행동의 연구를 수 있습니다.

비디오: Operant Sensation Seeking in the Mouse

A Procedure for Studying the Footshock-Induced Reinstatement of Cocaine Seeking in Laboratory Rats

The most insidious aspect of drug addiction is the high propensity for relapse. Animal models of relapse, known as reinstatement procedures, have been used extensively to study the neurobiology and phenomenology of relapse to drug use. Although procedural variations have emerged over the past several decades, the most conventional reinstatement procedures are based on the drug self-administration (SA) model. In this model, an animal is trained to perform an operant response to obtain drug. Subsequently, the behavior is extinguished by withholding response-contingent reinforcement. Reinstatement of drug seeking is then triggered by a discrete event, such as an injection of the training drug, re-exposure to drug-associated cues, or exposure to a stressor 1.
Reinstatement procedures were originally developed to study the ability of acute non-contingent exposure to the training drug to reinstate drug seeking in rats and monkeys 1, 2. Reinstatement procedures have since been modified to study the role of environmental stimuli, including drug-associated cues and exposure to various forms of stress, in relapse to drug seeking 1, 3, 4.
Over the past 15 years, a major focus of the reinstatement literature has been on the role of stress in drug relapse. One of the most commonly used forms of stress for studying this relationship is acute exposures to mild, intermittent, electric footshocks. The ability of footshock stress to induce reinstatement of drug seeking was originally demonstrated by Shaham and colleagues (1995) in rats with a history of intravenous heroin SA5. Subsequently, the effect was generalized to rats with histories of intravenous cocaine, methamphetamine, and nicotine SA, as well as oral ethanol SA 3, 6.
Although footshock-induced reinstatement of drug seeking can be achieved reliably and robustly, it is an effect that tends to be sensitive to certain parametrical variables. These include the arrangement of extinction and reinstatement test sessions, the intensity and duration of footshock stress, and the presence of drug-associated cues during extinction and testing for reinstatement. Here we present a protocol for footshock-induced reinstatement of cocaine seeking that we have used with consistent success to study the relationship between stress and cocaine seeking.

Animal models of relapse, known as reinstatement procedures, have been used extensively to study the role of stress in relapse to drug seeking. Here, we report on a method for inducing the reinstatement of cocaine seeking in laboratory rats via acute exposures to mild, intermittent electric footshock.

실험실 쥐의 추구 코카인 Footshock 유발 복직을 유학을위한 절차

The most insidious aspect of drug addiction is the high propensity for relapse.  Animal models of relapse, known as reinstatement procedures, have been ...

연구

신경과학

Multiple-mouse Neuroanatomical Magnetic Resonance Imaging

The field of mouse phenotyping with magnetic resonance imaging (MRI) is rapidly growing, motivated by the need for improved tools for characterizing and evaluating mouse models of human disease. MRI is an excellent modality for investigating genetically altered animals. It is capable of whole brain coverage, can be used in vivo, and provides multiple contrast mechanisms for investigating different aspects of neuranatomy and physiology. The advent of high-field scanners along with the ability to scan multiple mice simultaneously allows for rapid phenotyping of novel mutations.
Effective mouse MRI studies require attention to many aspects of experiment design. In this article, we will describe general methods to acquire quality images for mouse phenotyping using a system that images mice concurrently in shielded transmit/receive radio frequency (RF) coils in a common magnet (Bock et al., 2003). We focus particularly on anatomical phenotyping, an important and accessible application that has shown a high potential for impact in many mouse models at our imaging centre. Before we can provide the detailed steps to acquire such images, there are important practical considerations for both in vivo brain imaging (Dazai et al., 2004) and ex vivo brain imaging (Spring et al., 2007) that should be noted. These are discussed below.

Magnetic resonance imaging (MRI) has become an increasingly popular tool for examining the phenotype of genetically altered mice. This article illustrates the methods necessary to achieve high-throughput phenotyping of genetically altered mice using multiple-mouse MRI.

여러 마우스 Neuroanatomical 자기 공명 영상

The field of mouse phenotyping with magnetic resonance imaging (MRI) is rapidly growing, motivated by the need for improved tools for characterizing and ...

Detection of Neuritic Plaques in Alzheimer's Disease Mouse Model

Alzheimer's disease (AD) is the most common neurodegenerative disorder leading to dementia. Neuritic plaque formation is one of the pathological hallmarks of Alzheimer's disease. The central component of neuritic plaques is a small filamentous protein called amyloid &beta; protein (A&beta;)1, which is derived from sequential proteolytic cleavage of the beta-amyloid precursor protein (APP) by &beta;-secretase and &gamma;-secretase. The amyloid hypothesis entails that A&gamma;-containing plaques as the underlying toxic mechanism in AD pathology2. The postmortem analysis of the presence of neuritic plaque confirms the diagnosis of AD. To further our understanding of A&gamma; neurobiology in AD pathogenesis, various mouse strains expressing AD-related mutations in the human APP genes were generated. Depending on the severity of the disease, these mice will develop neuritic plaques at different ages. These mice serve as invaluable tools for studying the pathogenesis and drug development that could affect the APP processing pathway and neuritic plaque formation. In this protocol, we employ an immunohistochemical method for specific detection of neuritic plaques in AD model mice. We will specifically discuss the preparation from extracting the half brain, paraformaldehyde fixation, cryosectioning, and two methods to detect neurotic plaques in AD transgenic mice: immunohistochemical detection using the ABC and DAB method and fluorescent detection using thiofalvin S staining method.

Detection of Neuritic Plaques in Alzheimer&#039;s Disease Mouse Model

One of the pathological characteristics of AD is the formation of Amyloid &#x03B2; protein positive neuritic plaques. In this protocol we describe two methods to detect neuritic plaques in transgenic AD model mice: immunohistochemical detection using the ABC and DAB method and fluorescent detection using thioflavin S staining method.

알츠하이머 질병 마우스 모델에서 Neuritic Plaques의 감지

Alzheimer's disease (AD) is the most common neurodegenerative disorder leading to dementia. Neuritic plaque formation is one of the pathological hallmarks ...

The Mouse Forced Swim Test

The forced swim test is a rodent behavioral test used for evaluation of antidepressant drugs, antidepressant efficacy of new compounds, and experimental manipulations that are aimed at rendering or preventing depressive-like states. Mice are placed in an inescapable transparent tank that is filled with water and their escape related mobility behavior is measured. The forced swim test is straightforward to conduct reliably and it requires minimal specialized equipment. Successful implementation of the forced swim test requires adherence to certain procedural details and minimization of unwarranted stress to the mice. In the protocol description and the accompanying video, we explain how to conduct the mouse version of this test with emphasis on potential pitfalls that may be detrimental to interpretation of results and how to avoid them. Additionally, we explain how the behaviors manifested in the test are assessed.

The forced swim test is validated as an experimental approach to assess potential antidepressant efficacy in rodents. Experimental animals are placed in a tank of water and escape-related mobility behavior is quantified. The common procedures for the mouse version of this test are described.

마우스 강제 수영 시험

The forced swim test is a rodent behavioral test used for evaluation of antidepressant drugs, antidepressant efficacy of new compounds, and experimental ...

Microdialysis of Ethanol During Operant Ethanol Self-administration and Ethanol Determination by Gas Chromatography

Operant self-administration methods are commonly used to study the behavioral and pharmacological effects of many drugs of abuse, including ethanol. However, ethanol is typically self-administered orally, rather than intravenously like many other drugs of abuse. The pharmacokinetics of orally administered drugs are more complex than intravenously administered drugs. Because understanding the relationship between the pharmacological and behavioral effects of ethanol requires knowledge of the time course of ethanol reaching the brain during and after drinking, we use in vivo microdialysis and gas chromatography with flame ionization detection to monitor brain dialysate ethanol concentrations over time. 
Combined microdialysis-behavioral experiments involve the use of several techniques. In this article, stereotaxic surgery, behavioral training and microdialysis, which can be adapted to test a multitude of self-administration and neurochemical centered hypotheses, are included only to illustrate how they relate to the subsequent phases of sample collection and dialysate ethanol analysis. Dialysate ethanol concentration analysis via gas chromatography with flame-ionization detection, which is specific to ethanol studies, is described in detail. Data produced by these methods reveal the pattern of ethanol reaching the brain during the self-administration procedure, and when paired with neurochemical analysis of the same dialysate samples, allows conclusions to be made regarding the pharmacological and behavioral effects of ethanol.

A method to determine the time course of ethanol concentration in the brains of rats during operant ethanol self-administration is described. Gas chromatography with flame ionization detection is used to quantify ethanol in the dialysate samples, because it has the sensitivity required for the small volumes that are generated.

가스 크로마토 그래피에 의한 operant 에탄올 자기 관리 및 에탄올 결정시 에탄올의 Microdialysis

Operant self-administration methods are commonly used to study the behavioral and pharmacological effects of many drugs of abuse, including ethanol.  ...

A Simple Way to Measure Alterations in Reward-seeking Behavior Using Drosophila melanogaster

We describe a protocol for measuring ethanol self-administration in fruit flies (Drosophila melanogaster) as a proxy for changes in reward states. We demonstrate a simple way to tap into the fly reward system, modify experiences related to natural reward, and use voluntary ethanol consumption as a measure for changes in reward states. The approach serves as a relevant tool to study the neurons and genes that play a role in experience-mediated changes of internal state. The protocol is composed of two discrete parts: exposing the flies to rewarding and nonrewarding experiences, and assaying voluntary ethanol consumption as a measure of the motivation to obtain a drug reward. The two parts can be used independently to induce the modulation of experience as an initial step for further downstream assays or as an independent two-choice feeding assay, respectively. The protocol does not require a complicated setup and can therefore be applied in any laboratory with basic fly culture tools.

A Simple Way to Measure Alterations in Reward-seeking Behavior Using Drosophila melanogaster

We describe a protocol for inducing rewarding and nonrewarding experiences in fruit flies (Drosophila melanogaster) using voluntary ethanol consumption as a measure for changes in reward states.

사용 보상 추구 행동의 변화를 측정하는 간단한 방법<em&gt; 노랑 초파리</em

We describe a protocol for measuring ethanol self-administration in fruit flies (Drosophila melanogaster) as a proxy for changes in reward states. We ...

Operant Protocols for Assessing the Cost-benefit Analysis During Reinforced Decision Making by Rodents

Reinforcement-guided decision making is the ability to choose between competing courses of action based on the relative value of the benefits and their consequences. This process is integral to the normal human behavior and has been shown to be disrupted by neurological and psychiatric disorders such as addiction, schizophrenia, and depression. Rodents have long been used to uncover the neurobiology of human cognition. To this end, several behavioral tasks have been developed; however, most are non-automated and are labor-intensive. The recent development of the open-source microcontroller has enabled researchers to automate operant-based tasks for assessing a variety of cognitive tasks, standardizing the stimulus presentation, improving the data recording and consequently, improving the research output. Here, we describe an automated delay-based reinforcement-guided decision-making task, using an operant T-maze controlled by custom-written software programs. Using these decision-making tasks, we show the changes in the local field potential activities in the anterior cingulate cortex of a rat whilst it performs a delay-based cost-and-benefit decision-making task.

A cost-benefit analysis is a weighing-scale approach that the brain performs during the course of decision making. Here, we propose a protocol to train rats on an operant-based decision-making paradigm where rats choose higher rewards at the expense of waiting for 15 s to receive them.

설치류에 의해 강화 결정 시 비용-이익 분석을 평가 하기 위한 작동 프로토콜

Reinforcement-guided decision making is the ability to choose between competing courses of action based on the relative value of the benefits and their ...

Transpupillary Two-Photon In Vivo Imaging of the Mouse Retina

The retina transforms light signals from the environment into electrical signals that are propagated to the brain. Diseases of the retina are prevalent and cause visual impairment and blindness. Understanding how such diseases progress is critical to formulating new treatments. In vivo&#160;microscopy in animal models of disease is a powerful tool for understanding neurodegeneration and has led to important progress towards treatments of conditions ranging from Alzheimer&#39;s disease to stroke. Given that the retina is the only central nervous system structure inherently accessible by optical approaches, it naturally lends itself towards in vivo imaging. However, the native optics of the lens and cornea present some challenges for effective imaging access.
This protocol outlines methods for in vivo two-photon imaging of cellular cohorts and structures in the mouse retina at cellular resolution, applicable for both acute- and chronic-duration imaging experiments. It presents examples of retinal ganglion cell (RGC), amacrine cell, microglial, and vascular imaging using a suite of labeling techniques including adeno-associated virus (AAV) vectors, transgenic mice, and inorganic dyes. Importantly, these techniques extend to all cell types of the retina, and suggested methods for accessing other cellular populations of interest are described. Also detailed are example strategies for manual image postprocessing for display and quantification. These techniques are directly applicable to studies of retinal function in health and disease.

In vivo imaging is a powerful tool for the study of biology in health and disease. This protocol describes transpupillary imaging of the mouse retina with a standard two-photon microscope. It also demonstrates different in vivoimaging methods to fluorescently label multiple cellular cohorts of the retina.

경동공 이광자 마우스 망막의 생체 내 이미징

The retina transforms light signals from the environment into electrical signals that are propagated to the brain. Diseases of the retina are prevalent ...

In vivo Calcium Imaging in Mouse Inferior Olive

Inferior olive (IO), a nucleus in the ventral medulla, is the only source of climbing fibers that form one of the two input pathways entering the cerebellum. IO has long been proposed to be crucial for motor control and its activity is currently considered to be at the center of many hypotheses of both motor and cognitive functions of the cerebellum. While its physiology and function have been relatively well studied on single-cell level in vitro, presently there are no reports on the organization of the IO network activity in living animals. This is largely due to the extremely challenging anatomical location of the IO, making it difficult to subject to conventional fluorescent imaging methods, where an optic path must be created through the entire brain located dorsally to the region of interest.
Here we describe an alternative method for obtaining state-of-the-art -level calcium imaging data from the IO network. The method takes advantage of the extreme ventral location of the IO and involves a surgical procedure for inserting a gradient-refractive index (GRIN) lens through the neck viscera to come into contact with the ventral surface of the calcium sensor GCaMP6s-expressing IO in anesthetized mice. A representative calcium imaging recording is shown to demonstrate the feasibility to record IO neuron activity after the surgery. While this is a non-survival surgery and the recordings must be conducted under anesthesia, it avoids damage to life-critical brainstem nuclei and allows conducting large variety of experiments investigating spatiotemporal activity patterns and input integration in the IO. This procedure with modifications could be used for recordings in other, adjacent regions of the ventral brainstem.

In vivo Calcium Imaging in Mouse Inferior Olive

We present a protocol to expose the brainstem of adult mouse from the ventral side. By using a gradient-refractive index lens with a miniature microscope, calcium imaging can be used to examine the activity of inferior olive neural somata in vivo.

생체 내 마우스 열등올리브의 칼슘 이미징

Inferior olive (IO), a nucleus in the ventral medulla, is the only source of climbing fibers that form one of the two input pathways entering the ...

Using Optogenetics to Reverse Neuroplasticity and Inhibit Cocaine Seeking in Rats

This protocol demonstrates the steps needed to use optogenetic tools to reverse cocaine-induced plasticity at thalamo-amygdala circuits to reduce subsequent cocaine seeking behaviors in the rat. In our research, we had found that when rats self-administer intravenous cocaine paired with an audiovisual cue, synapses formed at inputs from the medial geniculate nucleus of the thalamus (MGN) onto principal neurons of the lateral amygdala (LA) become stronger as the cue-cocaine association is learned. We hypothesized that reversal of the cocaine-induced plasticity at these synapses would reduce cue-motivated cocaine seeking behavior. In order to accomplish this type of neuromodulation in vivo, we wanted to induce synaptic long-term depression (LTD), which decreases the strength of MGN-LA synapses. To this end, we used optogenetics, which allows neuromodulation of brain circuits using light. The excitatory opsin oChiEF was expressed on presynaptic MGN terminals in the LA by infusing an AAV containing oChiEF into the MGN. Optical fibers were then implanted in the LA and 473 nm laser light was pulsed at a frequency of 1 Hz for 15 minutes to induce LTD and reverse cocaine induced plasticity. This manipulation produces a long-lasting reduction in the ability of cues associated with cocaine to induce drug seeking actions.

The methods described here outline a procedure used to optogenetically reverse cocaine-induced plasticity in a behaviorally-relevant circuit in rats. Sustained low-frequency optical stimulation of thalamo-amygdala synapses induces long-term depression (LTD). In vivo optogenetically-induced LTD in cocaine-experienced rats resulted in the subsequent attenuation of cue-motivated drug seeking.