Bu proje NIH hibe DA19112 (DGW) ve DA026994 (CMO) tarafından desteklenmiştir. İllüstrasyon Katherine Louderback tarafından sağlanmıştır. Vanderbilt murin nörodavranışsal Laboratuvar deneyler yapıldı.

1. Bir güçlendiricidir gibi çeşitli görsel ve işitsel uyaranlara kullanarak edimsel test oturumlarını çalıştırmak için program yazınız. <ol><li> Sabit oranı (FR) oturumları için oturumu sırasında evin ışık ve fan açık oturumları bir saat uzunluğunda yapmak. Ilerici oranı oturumları için, uzunluğu iki saat oturumları olun. Iki kolu kolu hayvanlar (her bir hayvan için kolu atama asla değişmez) arasında &quot;aktif&quot; karşı &quot;aktif değil&quot; olarak belirlenmiş ve oturum dengelemek süresi uzatılmıştır. </li><li> Her güçlendiricidir aşağıdaki parametrelere göre çeşitlilik olduğunu böyle bir şekilde program kodu: <ul><li> 2, 4, 6 veya 8 sn: Her güçlendiricidir rastgele seçilen aşağıdaki süreler. </li><li> % 50 görev döngüsü ile 0.625, 1.25, 2.5, 5 Hz, her: her güçlendiricidir rastgele seçilen aşağıdaki uyarı lambası yanıp oranları. </li><li> her uyaran lamba flaş sol ya da odasının sağ tarafında ya da rastgele. </li><li> güçlendiricidir süresi için bir işitsel uyaran sağlamak; Laboratuvarımızda, biz odasında arka plan gürültü yukarıdaki ses yaklaşık 3 dB sağlayan bir infüzyon pompası tetikler. </li></ul></li><li> 1: gerçek zamanlı olarak aşağıdaki değerleri görüntülemek için program kodu. Aktif kolu presler, 2 sayısı. Inaktif kolu presler, 3 sayısı. Reinforcers, 4 sayısı. Zaman (0.1 saniye aralıklarla). </li></ol> 2. Hayvanlar (3 gün prosedürü) dikkatli <ol><li> Hayvan tesis aklimasyonundan sonra, hayvanların işleme başlar. Bu kaldırdı ve taşınmaları hayvanları alıştırarak. </li><li> Kafes içine eldivenli ellerini koyarak ve bunları 90 saniye boyunca oturup izin başlayın. Her fare o zaman ellerini araştırılmıştır değilse, farelerin doğru yavaşça elleri hareket ettirmek ve her biri sniff ve / veya devam etmeden önce ellerinizi iletişim için bekleyin. </li><li> Kuyruk tabanı tarafından tek her bir fare dikkatlice pick up ve elinizi koyun, hızlı bir şekilde yukarı kaldırarak ve fare kafes içine elinizi geri yürümeye izin geri getiren. </li><li> Fare tavır bağlı olarak, her bir fare 5-10 kez tekrarlayın. Bu yapıldığında son kez, günün bağlı olarak, belli bir süre için (elinize ayakta) fare yüksek tutun. 1. Gün: 5 saniye, 2 Gün: 10 sn, 3. Gün: 15 sn. Farenin her gün için bu kriter karşıladığından emin olun. Gün 1, kafesler arasında eldiven değiştirmek. </li><li> 2. Gün, inme hayvanın arka başlayarak fare eliniz açıkken. Ayrıca 2. Gün, hayvanların günlük ağırlığında başlar. Konu sayısını belirtmek için bir Sharpie her bir hayvanın kuyruk işaretleyin. </li><li> Enjeksiyonları deney sırasında verilecek ise, 2. Gün enjeksiyon fareler habituating başlar. Kafes tüm fareler ele gün için kriter yerine getirilmiş sonra yapılmalıdır. </li></ol> 3. Temiz ve test cihazları <ol><li> Alt pan sıcak su ile yıkayın. </li><li> Edimsel odasının duvar ve zeminler,% 30 etanol ile temizleyin. </li><li> , Ev ışık, fan ve uyarı ışıkları yanar kolları uzanır ve kayıtları kolu presler bir test programı çalıştırın. </li><li> Tüm ışıklar ve fanlar doğru çalıştığından emin olun ve tüm kolu presler kaydedilmesini sağlamak için programı test. </li><li> % 30 etanol ile temizleyin kolları. </li></ol> 4. Edimsel oturumu (oturumları günün aynı zamanda 5-6 gün / hafta) yapın <ol><li> Her fare tartılır. </li><li> Her odasına programı yükleyin ve deney uygun bir açıklama. Aktif kolu hayvanlar (yani aktif kolu, sol kolu farelerin yarısı için atanır; sağ kolu, diğer yarısı için aktif) arasında dengeli olmalıdır, ancak fare bir fare edildikten sonra aktif kolu yan asla değişmez atanır. </li><li> , Farenin her odaya Ulaştırma odasına yakın ve oturumu başlatmak. </li><li> Oturumu sona erdikten sonra, fareyi derhal kaldırmak ve kuyruk yeniden işareti. </li><li> Temizlik odaları Bölüm 3 olarak nitelendirdi. </li><li> Aktif ve etkin kolu presler sayısı için verileri analiz edin. Reinforcers ve / veya kolu doğruluğu (% aktif kolu presler) sayısı da rapor edilebilir. Fareler OSS bir tedavi etkisi için test olacak iseniz, test edilecek tüm fareler (örneğin satın alma kriterleri yerine getirdiğine dair sağlamak&gt; son üç FR-1 seans için 20 aktif kolu presler ve&gt;% 65 aktif kolu presler ) tedavi öncesinde başlamadan. </li><li> Edinimi sonra FR-1 donatı programı (örneğin, daha yüksek bir sabit oran, ilerici oran, rastgele oranı, vb) değiştirilebilir yanıt. </li></ol> 5. Temsilcisi Sonuçlar Şekil 1 (23 çoğaltılamaz), erkek C57Bl/6J fareler tarafından ÖSS satın alma bir örnek gösterilmiştir . Kontrol fare, aynı koşullar uygulanan iki kolu bu kolu presler hariç herhangi bir vergi politi vardısonucudur. Ni- Farelerin diğer kohort Şekil 2&#39;de gösterilmiştir. Başka bir grup, gıda takviye alırken bu deneyde, farelerin bir grup, ÖSS takviye aldı. Biz gıda ad libitum erişim koşulları altında, hem sabit ve ilerleyici oranı yanıt OSS ve emin olun (Şekil 2, A ve B)% 10 yanıt arasında benzer olduğunu buldular. Bu bir manipülasyon etkili karşılaştırmalar için açlık devlet ya da yanıt oranı farklılıklardan kaynaklanan potansiyel boşa önler iki farklı takviye türleri (duyusal ve gıda) sağlar. <img src="/files/ftp_upload/2292/2292fig1.jpg" alt="Şekil 1" /> Şekil 1: ÖSS fareler ve kontroller Kol presler inaktif kolu presler sonucu varken ÖSS fareler, her aktif kola basın (takviye FR-1 programı) sonra çeşitli görsel ve işitsel uyaranlar aldı. Kontrol fareler aynı şartlarda yapıldı ancak iki kolu (kolları hayvanlar boyunca aktif ve pasif ÖSS fareler için kolları dengeli olduğunu aynı şekilde 1 ve 2 belirtilir ve karşı dengeli) tuşuna basarak herhangi bir sonucu vardı. ÖSS fareler basarak Aktif kolu basarak inaktif kolu göre artmıştır (p &lt;0.05, ** p &lt;0.01) ve kontrolleri ile güçlendirilmiş olmayan kolu basarak (n = 7 8 $ p &lt;0.05, $ p &lt;0.01 .) 23 çoğaltılamaz Şekil. <img src="/files/ftp_upload/2292/2292fig2.jpg" alt="Şekil 2" /> Şekil 2: gıda için yanıt ÖSS fareler ve fareler tarafından Kol presler A.) Fareler ÖSS uyaran ya da gıda güçlendiricidir (% 10 sağlayın) için takviye bir FR-1 programı cevap verdi. Tüm fareler deneylerin süresi boyunca gıda reklam libidum erişim vardı. B.) FR-1 seans sonra, fareler beş gün boyunca ilerici bir takviye oranı (PR) yapılmaktadır ileri gitmişlerdi. Veriler, her bir hayvan için günde dört ve beş değerleri anlamına gelir temsil eder. Tamamlanmış nihai oranı sağ Y ekseni üzerinde rapor ve ilgili güçlendiricidir (yani 30 tepkiler daha önce dokuz reinforcers aldıktan sonra 10. güçlendiricidir elde etmek için gereklidir) elde etmek için gerekli yanıtların sayısı anlamına gelir.

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Arayan Edimsel hissi, fare, seçim hayvan intravenöz ilaç öz-yönetim için kullanışlı bir alternatif. Ne cerrahi ne de kateter bakım gerekli olduğunu aslında bu önemli teknik engellerin fare gibi avantajlıdır. Gıda gibi diğer doğal reinforcers ayrı takviye yönlerini ölçmek olabilir, çünkü ÖSS de çekici. Bu fare davranış önlemler, farklı çevre koşulları 24 arasında oldukça değişken olabilir not etmek yararlı olur . Bu sorun, ÖSS ile kendi labor...

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		<th>Material Name</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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<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

Edimsel yöntemler motive davranış çalışma için güçlü davranışsal araçlardır. Bu &#39;öz-yönetim&#39; yöntemleri yüksek yapı geçerliliği nedeniyle uyuşturucu bağımlılığı araştırma yaygın olarak kullanılmaktadır. Edimsel çalışmalar, bağımlılık sürecinin çeşitli yönleri preklinik araştırma için bir araç sağlar. Örneğin, akut takviye (ilaç ve ilaç dışı) mekanizmaları, öz-yönetim davranışı 1-6 etkilemek için bir moleküler hedef yeteneği belirlemek için farmakolojik veya genetik araçları kullanılarak test edilebilir . Ayrıca, ilaç veya yiyecek arayan davranışları, birincil güçlendiricidir yokluğunda okudu ve bu süreci bozmak için farmakolojik bileşikler yeteneği 3 bağımlılığı tedavisi için yararlı olabilir moleküler hedefleri ve bileşiklerin, keşif için bir preklinik model olabilir 7-9. Bir sorun fare intravenöz ilaç öz-yönetim çalışmaları gerçekleştirirken, teknik zorluk kateter açıklık sürdürmenin. Bu deneylerde Aşınma oranları yüksektir ve% 40 veya daha yüksek 10-15 ulaşabilirsiniz. Öz-yönetim ile ilgili başka bir ilaç genel bir sorun, güçlendiricidir farmakolojik kaynaklanan etkileri belirli davranışlar üretmek seçici. Örneğin, takviye ve nörolojik etkiler psikostimülanların ölçümü, psikomotor etkileri eleştirilmiştir olabilir. Gıda takviye Edimsel yöntemler kullanarak, uyuşturucu madde bağımlılığı eğitimi kendi programını ilaç öz-yönetim değiştiren bazı manipülasyonlar gıda öz-yönetim üzerinde çok az etkisi olduğu gerçeğini ile sınırlı olmasına rağmen, bu tuzaklar önleyebilirsiniz. Örneğin, mezolimbik dopamin D1 dopamin reseptör lezyon veya bayıltıcı gıda öz-yönetim 12,16 üzerinde önemli bir etkiye sahip olmadan kendi kendini idare kokain azaltır. Duyusal uyaranların birincil reinforcers (yani şartlandırılmış değil reinforcers) 17-22 olarak yanıt edimsel destek yeteneklerini için tarif edilmiştir. İşitsel ve görsel uyaranlara kendi kendini idare şaşırtıcı bu takviye altında yatan nöral mekanizmalar hakkında çok az bilinmesine rağmen, birkaç tür 18,21,23 . (ÖSS) modeli arayan edimsel hissi, duyusal takviye 24 nöral mekanizmaların çalışma sağlayan önemli, fare duyusal öz-yönetim elde etmek için sağlam bir model . ÖSS ek bir avantajı bağımlılığı ile ilgili olabilir edimsel davranış farklılıkları mutant fareler ekrana yeteneğidir. Biz daha önce psikostimülan öz-yönetim eksikliği olduğu gösterilmiştir dopamin D1 reseptörü knockout farelerde, ÖSS 24 elde etmek için başarısız olduğunu bildirdin . Bu, bu farelerin bir güçlendiricidir gıda olarak kullanıldığında, bir edimsel görev öğrenme yeteneğine sahip olduğu benzersiz bir bulgudur. Gıda takviye kullanarak edimsel çalışmalar, genel motive davranış ve yukarıda da belirtildiği gibi, altta yatan gıda takviye, çalışmada kullanışlı olabilir, ancak bu çalışmalar, uyuşturucu bağımlılığı moleküler mekanizmalar eğitim uygulama sınırlıdır. Böylece, ÖSS uyuşturucu bağımlılığı süreçlerin çalışma için özellikle çekici bir model yapacak gıda takviye, farklı duyusal ve psikostimülan takviye aracılık benzer nöral substratlar olabilir. OSS ve ilaç reinforcers diğer moleküler hedefleri arasında örtüşme derecesi belli değildir, ama şu anda peşinde olduğu bir konudur. Bağımlılığı yok direnç gibi bazı yönlerini, ÖSS ile birlikte görülebilir, eskalasyon 25 24 Bu model gözlenen olmadığını bulduk . İlginçtir, sakaroz 26 öz-yönetimi ile alımı ve bağımlılığının diğer bazı yönlerini tırmanması görülmektedir. Böylece, ilaç dışı edimsel prosedürler bağımlılığı ile ilgili süreçlerde çalışma istenen, gıda ya da duyusal reinforcers soruluyor belirli bir soruyu en iyi uyacak şekilde seçilmiş olabilir. Sonuç olarak, gıda öz-yönetim ve fare ÖSS hem de yüksek verim, motivasyon katılan nöral hedefleri farmakolojik veya genetik manipülasyon etkilerini incelemek amacıyla gelir sağlayan bir intravenöz kateter gerektirmeyen bir avantaja sahip. Bir güçlendiricidir gibi gıda kullanarak edimsel test gıda alımının düzenlenmesi çalışmalarında özellikle yararlı olsa da, ÖSS, özellikle duyusal uyaranlar takviye mekanizmaları çalışmak için apt ve yenilik arayan ve bağımlılığı geniş uygulanabilirliği olabilir.

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

Operant Sensation Seeking in the Mouse

Bu protokolde güçlendiricidir bir fare gibi duyusal uyaranlar kullanılarak edimsel öğrenme yöntemi açıklar. Bu, önceden herhangi bir eğitim ya da gıda kısıtlama gerektirir ve onu motive davranış, gıda olarak farmakolojik veya doğal bir güçlendiricidir kullanımı olmadan çalışma sağlar.

Fare Aradığınız Edimsel Sensation

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 Görüntüleme.  Vanderbilt University Medical Center. Bu protokolde güçlendiricidir bir fare gibi duyusal uyaranlar kullanılarak edimsel öğrenme yöntemi açıklar. Bu, önceden herhangi bir eğitim ya da gıda kısıtlama gerektirir ve onu motive davranış, gıda olarak farmakolojik veya doğal bir güçlendiricidir kullanımı olmadan çalışma sağlar.

Video: 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.

Laboratuar Farelerinde Aradığınız Kokain Footshock Bağlı Yürürlüğe Girmesi incelenmesi için Usulü

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

Nörobilim

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.

Çoklu-fare nöroanatomik Manyetik Rezonans Görüntüleme

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.

Nöritik plaklar Alzheimer Hastalığı Fare Modeli Algılama

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.

Fare Zorla Swim Testi

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.

Gaz kromatografisi ile operant etanol kendi kendine uygulama ve etanol belirleme sırasında etanol mikrodivaliz

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.

Kullanımı Ödül arayan davranış değişiklikleri Tedbir Basit Yolu<em&gt; Drosophila melanogaster</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.

Kemirgenler tarafından güçlendirilmiş karar verme sırasında maliyet-fayda analizi değerlendirmek için operant protokolleri

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.

Transpupiller İki Foton Fare Retinasının In vivo Görüntülenmesi

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.

In vivo Fare Kalitesiz Zeytinde Kalsiyum Görüntüleme

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.