Name: paw-dragging: a novel, sensitive analysis of the mouse cylinder test
Uploaded: 2015-04-29T16:00:00
Description: Watch this Scientific Journal Video about Paw-Dragging: a Novel, Sensitive Analysis of the Mouse Cylinder Test at JoVE.com

Vi tackar John Crowell och Mr Terry Upshall för sin tekniska expertis och hjälp med fotografering och filmning. Detta arbete stöddes av verksamhetsbidrag till JLV från den kanadensiska Institutes of Health Research och forskning och utveckling AB i Newfoundland och en hjärta &amp; Stroke Foundation of Canada Canadian Partnerskap för stroke Recovery Catalyst bidrag. RBR var mottagare av en Keith Griffiths Memorial hjärta &amp; Stroke Foundation Graduate Scholarship.

Etik uttalande: Alla experiment har godkänts av Memorial University of Newfoundland Animal Care etikkommitté enligt riktlinjerna i den kanadensiska rådet om Animal Care. 1. Möss <ol><li> Använd vuxna möss. I denna studie var vuxna manliga FVBN möss (n = 10) mellan 2-4 månader användes. House möss på en 12:12 h omvänd ljus-mörker cykel och ge standard gnagarfoder och vatten efter behag. </li></ol> 2. Material som krävs för cylindern Test <ol><li> Skaffa ett bord...

<ol>
	<li>Schallert, T., Fleming, S. M., Leasure, J. L., Tillerson, J. L., Bland, S. T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=CNS+plasticity+and+assessment+of+forelimb+sensorimotor+outcome+in+unilateral+rat+models+of+stroke,+cortical+ablation,+parkinsonism+and+spinal+cord+injury.">CNS plasticity and assessment of forelimb sensorimotor outcome in unilateral rat models of stroke, cortical ablation, parkinsonism and spinal cord injury.</a> Neuropharmacology. 39, 777-787 (2000).</li><li>Kolb, B., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Growth+factor-stimulated+generation+of+new+cortical+tissue+and+functional+recovery+after+stroke+damage+to+the+motor+cortex+of+rats.">Growth factor-stimulated generation of new cortical tissue and functional recovery after stroke damage to the motor cortex of rats.</a> J Cereb Blood Flow Metab. 27 (5), 983-997 (2007).</li><li>Windle, V., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=An+analysis+of+four+different+methods+of+producing+focal+cerebral+ischemia+with+endothelin-1+in+the+rat.">An analysis of four different methods of producing focal cerebral ischemia with endothelin-1 in the rat.</a> Exp Neurol. 201 (2), 324-334 (2006).</li><li>Roome, R. B., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+reproducible+Endothelin-1+model+of+forelimb+motor+cortex+stroke+in+the+mouse.">A reproducible Endothelin-1 model of forelimb motor cortex stroke in the mouse.</a> J Neurosci Methods. 233, 34-44 (2014).</li><li>Tennant, K. A., Jones, T. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Sensorimotor+behavioral+effects+of+endothelin-1+induced+small+cortical+infarcts+in+C57BL/6+mice.">Sensorimotor behavioral effects of endothelin-1 induced small cortical infarcts in C57BL/6 mice.</a> J Neurosci Methods. 181 (1), 18-26 (2009).</li><li>Wang, Y., Jin, K., Greenberg, D. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Neurogenesis+associated+with+endothelin-induced+cortical+infarction+in+the+mouse.">Neurogenesis associated with endothelin-induced cortical infarction in the mouse.</a> Brain Res. 1167, 118-122 (2007).</li><li>Baskin, Y. K., Dietrich, W. D., Green, E. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Two+effective+behavioral+tasks+for+evaluating+sensorimotor+dysfunction+following+traumatic+brain+injury+in+mice.">Two effective behavioral tasks for evaluating sensorimotor dysfunction following traumatic brain injury in mice.</a> J Neurosci Methods. 129 (1), 87-93 (2003).</li><li>Li, X., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Chronic+behavioral+testing+after+focal+ischemia+in+the+mouse:+functional+recovery+and+the+effects+of+gender.">Chronic behavioral testing after focal ischemia in the mouse: functional recovery and the effects of gender.</a> Exp Neurol. 187 (1), 94-104 (2004).</li><li>Clarke, J., Ploughman, M., Corbett, D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+qualitative+and+quantitative+analysis+of+skilled+forelimb+reaching+impairment+following+intracerebral+hemorrhage+in+rats.">A qualitative and quantitative analysis of skilled forelimb reaching impairment following intracerebral hemorrhage in rats.</a> Brain Res. , 204-212 (2007).</li><li>Montoya, C. P., Campbell-Hope, L. J., Pemberton, K. D., Dunnett, S. B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+'staircase+test':+a+measure+of+independent+forelimb+reaching+and+grasping+abilities+in+rats.">The 'staircase test': a measure of independent forelimb reaching and grasping abilities in rats.</a> J Neurosci Methods. 36 (2-3), 219-228 (1991).</li><li>Farr, T. D., Whishaw, I. Q. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Quantitative+and+qualitative+impairments+in+skilled+reaching+in+the+mouse+(Mus+musculus)+after+a+focal+motor+cortex+stroke.">Quantitative and qualitative impairments in skilled reaching in the mouse (Mus musculus) after a focal motor cortex stroke.</a> Stroke. 33 (7), 1869-1875 (2002).</li><li>Tennant, K. A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+vermicelli+and+capellini+handling+tests:+simple+quantitative+measures+of+dexterous+forepaw+function+in+rats+and+mice.">The vermicelli and capellini handling tests: simple quantitative measures of dexterous forepaw function in rats and mice.</a> J Vis Exp. (41), (2010).</li><li>Clarkson, A. N., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=AMPA+receptor-induced+local+brain-derived+neurotrophic+factor+signaling+mediates+motor+recovery+after+stroke.">AMPA receptor-induced local brain-derived neurotrophic factor signaling mediates motor recovery after stroke.</a> J Neurosci. 31 (10), 3766-3775 (2011).</li><li>Clarkson, A. N., Huang, B. S., Macisaac, S. E., Mody, I., Carmichael, S. T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Reducing+excessive+GABA-mediated+tonic+inhibition+promotes+functional+recovery+after+stroke.">Reducing excessive GABA-mediated tonic inhibition promotes functional recovery after stroke.</a> Nature. 468 (7321), 305-309 (2010).</li></ol>

De viktigaste punkterna för att fastställa när kvantifiera tass-dra beteende i cylinder testet är följande: i) kvantifiera antalet tass-drar kontra totala tass handen för varje tass före hjärnskada att etablera en baslinje; ii) kvantifiera antalet tass-laggar kontra totala tass handen för varje tass efter ischemisk skada; och iii) skilja mellan en tass-dra och den laterala rörelsen hos tassen längs cylinderväggen under sidovridning av musen torso. Paw-släp är en ny beteende som...

Målet med neurala föryngringsstrategier är att visa både vävnad reparera och funktionell återhämtning. Funktionell återhämtning typiskt utvärderas med beteendetester som mäter funktionella brister, i detta fall med motorik som är förknippade med skador på specifika delar av hjärnan. Traumatisk hjärnskada eller ischemisk skada på sensorimotor forelimb området av hjärnbarken kan påvisas genom ett antal beteendetester. Ett sådant test är cylinder testet används flitigt i råttor för att bedöma funktionella brister i frambensaktivitet 1. Testet har en låg set-up kostnad som endast kräver en cylinder, kamera och bord med en transparent topp. Det är lätt att administrera eftersom den är baserad på den naturliga undersökande beteende hos gnagare, så pre-utbildning och brist på mat eller belöningar behövs inte. Trots dessa många fördelar, är cylindertestet underutnyttjade att bedöma forelimb underskott i möss efter brännskador till forelimb sensorimotor cortex, som vi tillskriver den analys av mus beteende i cylindertest. Forelimb asymmetri är den klassiska måttet på analys för cylindertest. När den placeras i cylindern, gnagare utforska naturligtvis väggarna i cylindern genom uppfödning på sina bakben och vidrör cylinderväggarna med sina forelimb tassar för postural balans. Antalet tass handen med väggen med varje forelimb lätt kvantifieras genom att filma gnagare under denna utforskning av cylindern. Forelimb asymmetri uppstår när påverkade frambens tassen gör färre handen med väggen än den opåverkade frambens tassen och är en indikation på skador på det kontra sensorimotorisk kortex. Hos råttor, intra-kortikala injektioner av kärlsammandragande medel, Endotelin (ET-1), i forelimb sensorimotor cortex orsakar en fokal ischemisk skada, vilket resulterar i beteendestörningar i den kontralaterala forelimb. Brister i kontra forelimb användning lätt detekteras som förändringar i forelimb asymmetri i cylinder-testet på råttor 1-3. I motsats till råttor dock förändringar i forelimb asymmetri är rörlig och mindre konsekventa i möss efter jämförbara ET-1 injektioner 4-6. Här visar vi en ny analys av forelimb beteende i cylindertestet - analys av tass-dra beteende. Vi har tidigare visat att tass-drar analys är ett mer känsligt mått på skada på forelimb sensorimotor kortex i möss än den klassiska frambens asymmetri analys och därför kan tillämpas på en mängd olika fokala kortikala skademodeller. Undersökning av hur framtassarna i kontakt med cylinderväggen efter ischemisk skada forelimb sensorimotor cortex avslöjade en ny beteende hos möss - tass-dra 4. En tass-dra inträffar när en mus står på bakbenen för att utforska cylinderväggen då drar dess påverkade (kontra lesional) tass längs cylinderväggen mot dess mittlinje eller nedåt väggen medandess opåverkade tassarna ger postural stöd mot väggen. Paw-laddar sällan förekommer i oskadade möss därför utseendet på en tass-dra är en positiv indikator för skador på forelimb sensorimotor cortex 4. Vi har tidigare kvantifierats tass-dra beteende hos möss efter ET-1 ischemisk skada forelimb sensorimotor cortex och har visat ihållande tass-dra beteende hos möss upp till två veckor efter stroke 4. Här visar vi att tass-dra beteende upprätthålls upp till fyra veckor efter stroke. Analys av tass-dra beteende ger en ny och känslig verktyg för att bedöma fokal ischemisk skada forelimb sensorimotor cortex hos möss. Dess billiga set-up, enkel administration och scoring gör detta till en enkel, men ändå användbart verktyg för att snabbt bedöma forelimb beteendestörningar hos möss.

<table border="0" cellpadding="0" cellspacing="0">
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		<tr>
			<td>Plexi-glass cylinder</td>
			<td>N/A</td>
			<td>N/A</td>
			<td>17.5cm high, 9.5cm outer diameter, 8.8cm inner diameter, wall thickness 0.35cm (or 3.5 mm)</td>
		</tr>
		<tr>
			<td>viewing table</td>
			<td>N/A</td>
			<td>N/A</td>
			<td>54x56x66.5cm (width x length x height), top of table is a 51x51cm sheet of plexiglass.</td>
		</tr>
		<tr>
			<td>mirror</td>
			<td>N/A</td>
			<td>N/A</td>
			<td>34x58cm mirror</td>
		</tr>
		<tr>
			<td>video camera</td>
			<td>Sony</td>
			<td>DCR-SR42</td>
			<td>Video camera with onboard storage, SD functionality, 40x optical zoom</td>
		</tr>
		<tr>
			<td>computer</td>
			<td>Dell</td>
			<td>Optiplex 760</td>
			<td>Processor: Intel, 3.0 GHz, Memory 4.00GB (RAM)&#160;</td>
		</tr>
		<tr>
			<td>computer monitor</td>
			<td>Samsung</td>
			<td>S22C350H</td>
			<td></td>
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		<tr>
			<td>Excel (Microsoft Office Professional Plus)</td>
			<td>Microsoft</td>
			<td>v14.0.7106.5003</td>
			<td></td>
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			<td>VLC Media Player</td>
			<td>Video LAN</td>
			<td>v2.1.2</td>
			<td>Media player with playback speed modulation and video support</td>
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		<tr>
			<td>External Hard Drive</td>
			<td>Western Digital</td>
			<td>WDBAAU0020HBK-01</td>
			<td>2 TB</td>
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paw-dragging: a novel, sensitive analysis of the mouse cylinder test

Cylindern testet rutinmässigt används för att förutsäga fokal ischemisk skada forelimb motor cortex hos gnagare. När den placeras i cylindern, gnagare utforska med uppfödning och vidrör väggarna i cylindern med sina forelimb tassar för postural stöd. Efter ischemisk skada forelimb sensorimotor cortex, råttor förlita sig mer tungt på deras opåverkade forelimb tass för postural stöd resulterar i färre handen med sin påverkade tassen som kallas frambens asymmetri. Däremot fokal ischemisk skada i mushjärna inte resultera i jämförbara konsekvent underskott i forelimb asymmetri. Medan frambens asymmetri underskott sällan observeras, inte möss visar en ny beteende efter stroke kallas &quot;tass-släp&quot;. Paw-släp är tendensen för en mus för att dra sitt påverkade tassen längs cylinderväggen snarare än direkt skjuta ifrån från väggen när demontering från en bakre till en fyrbent hållning. Vi har tidigare visat atttass-dra beteende är mycket känslig för små kortikala ischemiska skador på forelimb motoriska cortex. Här ger vi ett detaljerat protokoll för tass-dra analys. Vi definierar vad en tass-dra är och visa hur man kvantifiera tass-dra beteende. Cylindern testet är ett enkelt och billigt test för att administrera och inte kräver förberedande utbildning eller livsmedels utsatthet strategier. Vid användning av tass-dra analys med cylinderprovningen, fyller en nisch för att förutsäga kortikala ischemiska skador såsom photothrombosis och endotelin-1 (ET-1) inducerad ischemi - två modeller som ständigt ökar i popularitet och producerar mindre brännskador än arteria cerebri media ocklusion. Slutligen kommer mäta tass-dra beteende i cylindertestet tillåta studier av funktionell återhämtning efter kortikal skada med en bred kohort av transgena musstammar där tidigare frambens asymmetri analys har misslyckats med att upptäcka konsekvent underskott.

Vi har tidigare visat att tass-dra beteende visas efter en fokal ischemisk skada forelimb sensorimotor cortex och är en positiv indikator på skada 4. Intra-kortikala injektioner av ET-1 i forelimb sensorimotor cortex användes för att framkalla en ischemisk skada (Figur 8A, B). Denna studie undersökte huruvida tass-dra beteende förlängas längre än 14 dagar efter skada för dess potentiella användning för att bedöma funktionell återhämtning. Möss testades i cylinder test på dag ...

Watch this Scientific Journal Video about Paw-Dragging: a Novel, Sensitive Analysis of the Mouse Cylinder Test at JoVE.com

Paw-Dragging: a Novel, Sensitive Analysis of the Mouse Cylinder Test

Klassisk frambens asymmetri analys av cylinder testet rutinmässigt används för att bedöma beteendestörningar hos råttor efter hjärnskada eller stroke; men misslyckas att upptäcka konsekvent underskott i möss. Denna studie visar att kvantifiera tass-släp beteende är en känsligare analys av hjärnskada hos möss.

Tafsa-dra: en roman, känslig analys av mus Cylinder Test

The cylinder test is routinely used to predict focal ischemic damage to the forelimb motor cortex in rodents. When placed in the cylinder, rodents explore ...

paw-dragging-a-novel-sensitive-analysis-of-the-mouse-cylinder-test

Research

JoVE Journal

Behavior

Inchworming: A Novel Motor Stereotypy in the BTBR T+ Itpr3tf/J Mouse Model of Autism

Autism Spectrum Disorder (ASD) is a behaviorally defined neurodevelopmental disorder characterized by decreased reciprocal social interaction, abnormal communication, and repetitive behaviors with restricted interest. As diagnosis is based on clinical criteria, any potentially relevant rodent models of this heterogeneous disorder should ideally recapitulate these diverse behavioral traits. The BTBR T+ Itpr3tf/J (BTBR) mouse is an established animal model of ASD, displaying repetitive behaviors such as increased grooming, as well as cognitive inflexibility. With respect to social interaction and interest, the juvenile play test has been employed in multiple rodent models of ASD. Here, we show that when BTBR mice are tested in a juvenile social interaction enclosure containing sawdust bedding, they display a repetitive synchronous digging motion. This repetitive motor behavior, referred to as &#34;inchworming,&#34; was named because of the stereotypic nature of the movements exhibited by the mice while moving horizontally across the floor. Inchworming mice must use their fore- and hind-limbs in synchrony to displace the bedding, performing a minimum of one inward and one outward motion. Although both BTBR and C56BL/6J (B6) mice exhibit this behavior, BTBR mice demonstrate a significantly higher duration and frequency of inchworming and a decreased latency to initiate inchworming when placed in a bedded enclosure. We conclude that this newly described behavior provides a measure of a repetitive motor stereotypy that can be easily measured in animal models of ASD.

Inchworming: A Novel Motor Stereotypy in the BTBR T+ Itpr3tf/J Mouse Model of Autism

Inchworming is a highly repetitive synchronous digging motion displayed by BTBR T+ Itpr3tf/J (BTBR) mice when placed in a testing cage with sufficient sawdust bedding. The procedure is a modification of the juvenile social interaction protocol and is used here to assess repetitive motor stereotypies relevant to Autism Spectrum Disorder.

Inchworming: A Novel Motor stereotypi i BTBR<em&gt; T<sup&gt; +</sup&gt; Itpr3<sup&gt; Tf</sup</em&gt; / J musmodell av Autism

Autism Spectrum Disorder (ASD) is a behaviorally defined neurodevelopmental disorder characterized by decreased reciprocal social interaction, abnormal ...

Contextual and Cued Fear Conditioning Test Using a Video Analyzing System in Mice

The contextual and cued fear conditioning test is one of the behavioral tests that assesses the ability of mice to learn and remember an association between environmental cues and aversive experiences. In this test, mice are placed into a conditioning chamber and are given parings of a conditioned stimulus (an auditory cue) and an aversive unconditioned stimulus (an electric footshock). After a delay time, the mice are exposed to the same conditioning chamber and a differently shaped chamber with presentation of the auditory cue. Freezing behavior during the test is measured as an index of fear memory. To analyze the behavior automatically, we have developed a video analyzing system using the ImageFZ application software program, which is available as a free download at http://www.mouse-phenotype.org/. Here, to show the details of our protocol, we demonstrate our procedure for the contextual and cued fear conditioning test in C57BL/6J mice using the ImageFZ system. In addition, we validated our protocol and the video analyzing system performance by comparing freezing time measured by the ImageFZ system or a photobeam-based computer measurement system with that scored by a human observer. As shown in our representative results, the data obtained by ImageFZ were similar to those analyzed by a human observer, indicating that the behavioral analysis using the ImageFZ system is highly reliable. The present movie article provides detailed information regarding the test procedures and will promote understanding of the experimental situation.

This article presents a protocol for a contextual and cued fear conditioning test using a video analyzing system to assess fear learning and memory in mice.

Kontextuell och cued rädsla Conditioning Test Med hjälp av en videoanalyssystem hos möss

The contextual and cued fear conditioning test is one of the behavioral tests that assesses the ability of mice to learn and remember an association ...

The Forced Swim Test as a Model of Depressive-like Behavior

The goal of the present protocol is to describe the forced swim test (FST), which is one of the most commonly used assays for the study of depressive-like behavior in rodents. The FST is based on the assumption that when placing an animal in a container filled with water, it will first make efforts to escape but eventually will exhibit immobility that may be considered to reflect a measure of behavioral despair. This test has been extensively used because it involves the exposure of the animals to stress, which was shown to have a role in the tendency for major depression. Additionally, the FST has been shown to share some of the factors that are influenced or altered by depression in humans, including changes in food consumption, sleep abnormalities and drug-withdrawal-induced anhedonia. The main advantages of this procedure are that it is relatively easy to perform and that its results are easily and quickly analyzed. Moreover, its sensitivity to a broad range of antidepressant drugs that makes it a suitable screening test is one of the most important features leading to its high predictive validity. Despite its appeal, this model has a number of disadvantages. First, the issue of chronic augmentation is problematic in this test because in real life patients need to be treated for at least several weeks before they experience any relief from their symptoms. Last, due to the aversiveness of the FST, it is important to take into account possible influences it might have on brain structure/function if brain analyses are to be carried out following this procedure.

This protocol describes the forced swim test, which is used for the study of depressive-like behavior in rodents. This procedure involves placing an animal in a container filled with water that eventually will lead to the exhibition of immobility behavior, which is considered to reflect behavioral despair.

Den Tvingad Simma Test som en modell för Depressiva liknande beteende

The goal of the present protocol is to describe the forced swim test (FST), which is one of the most commonly used assays for the study of depressive-like ...

Morris Water Maze Test: Optimization for Mouse Strain and Testing Environment

The Morris water maze (MWM) is a commonly used task to assess hippocampal-dependent spatial learning and memory in transgenic mouse models of disease, including neurocognitive disorders such as Alzheimer&#8217;s disease. However, the background strain of the mouse model used can have a substantial effect on the observed behavioral phenotype, with some strains exhibiting superior learning ability relative to others. To ensure differences between transgene negative and transgene positive mice can be detected, identification of a training procedure sensitive to the background strain is essential. Failure to tailor the MWM protocol to the background strain of the mouse model may lead to under- or over- training, thereby masking group differences in probe trials. Here, a MWM protocol tailored for use with the F1 FVB/N x 129S6 background is described. This is a frequently used background strain to study the age-dependent effects of mutant P301L tau (rTg(TauP301L)4510 mice) on the memory deficits associated with Alzheimer&#8217;s disease. Also described is a strategy to re-optimize, as dictated by the particular testing environment utilized.

This manuscript describes a Morris water maze (MWM) protocol tailored for use with a commonly used mouse model of Alzheimer's disease. The MWM is widely used in transgenic mouse models. Implementation of a procedure sensitive to the background strain of the mouse model is essential for detecting group differences.

Morris Water Maze Test: Optimering för musstammen och Testmiljö

 The Morris water maze (MWM) is a commonly used task to assess hippocampal-dependent spatial learning and memory in transgenic mouse models of disease, ...

A Novel Approach to Assess Motor Outcome of Deep Brain Stimulation Effects in the Hemiparkinsonian Rat: Staircase and Cylinder Test

Deep brain stimulation of the subthalamic nucleus is an effective treatment option for Parkinson&#39;s disease. In our lab we established a protocol to screen different neurostimulation patterns in hemiparkinsonian (unilateral lesioned) rats. It consists of creating a unilateral Parkinson&#39;s lesion by injecting 6-hydroxydopamine (6-OHDA) into the right medial forebrain bundle, implanting chronic stimulation electrodes into the subthalamic nucleus and evaluating motor outcomes at the end of 24 hr periods of cable-bound external neurostimulation. The stimulation was conducted with constant current stimulation. The amplitude was set 20% below the individual threshold for side effects. The motor outcome evaluation was done by the assessment of spontaneous paw use in the cylinder test according to Shallert and by the assessment of skilled reaching in the staircase test according to Montoya. This protocol describes in detail the training in the staircase box, the cylinder test, as well as the use of both in hemiparkinsonian rats. The use of both tests is necessary, because the staircase test seems to be more sensitive for fine motor skill impairment and exhibits greater sensitivity to change during neurostimulation. The combination of the unilateral Parkinson model and the two behavioral tests allows the assessment of different stimulation parameters in a standardized way.

Deep brain stimulation (DBS) is an effective treatment option for Parkinson's disease. We established a study design to screen novel stimulation paradigms in rats. The protocol describes the use of the staircase test and cylinder test for motor outcome assessment in DBS treated hemiparkinsonian rats.

En ny metod för att bedöma Motor Resultat av Deep Brain Stimulation effekter i Hemiparkinsonian Rat: Trappa och Cylinder Test

Deep brain stimulation of the subthalamic nucleus is an effective treatment option for Parkinson&#39;s disease. In our lab we established a protocol to ...

The Treadmill Fatigue Test: A Simple, High-throughput Assay of Fatigue-like Behavior for the Mouse

Fatigue is a prominent symptom in many diseases and disorders and reduces quality of life for many people. The lack of clear pathogenesis and failure of current interventions to adequately treat fatigue in all patients leaves a need for new treatment options. Despite the therapeutic need and importance of preclinical research in helping identify promising novel treatments, few preclinical assays of fatigue are available. Moreover, the most common preclinical assay used to assess fatigue-like behavior, voluntary wheel running, is not suitable for use with some strains of mice, may not be sensitive to drugs that reduce fatigue, and has relatively low throughput. The current protocol describes a novel, non-voluntary preclinical assay of fatigue-like behavior, the treadmill fatigue test, and provides evidence of its efficacy in detecting fatigue-like behavior in mice treated with a chemotherapy drug known to cause fatigue in humans and fatigue-like behavior in animals. This assay may be a beneficial alternative to wheel running, as fatigue-like behavior and potential interventions can be assessed in a greater number of mice over a shorter time frame, thus permitting faster discovery of new therapeutic options.

Fatigue is a common, undertreated and frequently poorly-understood symptom in many diseases and disorders. New preclinical assays of fatigue may help to improve current understanding and future treatment of fatigue. To that end, the current protocol provides a novel means of measuring fatigue-like behavior in the mouse.

Löpbandet Trötthet Test: En enkel, med hög kapacitet Analys av trötthet-liknande beteende för musen

Fatigue is a prominent symptom in many diseases and disorders and reduces quality of life for many people. The lack of clear pathogenesis and failure of ...

The 4 Mountains Test: A Short Test of Spatial Memory with High Sensitivity for the Diagnosis of Pre-dementia Alzheimer's Disease

This protocol describes the administration of the 4 Mountains Test (4MT), a short test of spatial memory, in which memory for the topographical layout of four mountains within a computer-generated landscape is tested using a delayed match-to-sample paradigm. Allocentric spatial memory is assessed by altering the viewpoint, colors and textures between the initially presented and target images.
Allocentric spatial memory is a key function of the hippocampus, one of the earliest brain regions to be affected in Alzheimer&#39;s disease (AD) and impairment of hippocampal function predates the onset of dementia. It was hypothesized that performance on the 4MT would aid the diagnosis of predementia AD, which manifests clinically as Mild Cognitive Impairment (MCI).
The 4MT was applied to patients with MCI, stratified further based on cerebrospinal fluid (CSF) AD biomarker status (10 MCI biomarker positive, 9 MCI biomarker negative), and with mild AD dementia, as well as healthy controls. Comparator tests included tests of episodic memory and attention widely accepted as sensitive measures of early AD. Behavioral data were correlated with quantitative MRI measures of the hippocampus, precuneus and posterior cingulate gyrus.
4MT scores were significantly different between the two MCI groups (p = 0.001), with a test score of &#8804;8/15 associated with 100% sensitivity and 78% specificity for the classification of MCI with positive AD biomarkers, i.e., predementia AD. 4MT test scores correlated with hippocampal volume (r = 0.42) and cortical thickness of the precuneus (r = 0.55).
In conclusion, the 4MT is effective in identifying the early stages of AD. The short duration, easy application and scoring, and favorable psychometric properties of the 4MT fulfil the need for a simple but accurate diagnostic test for predementia AD.

The 4 Mountains Test: A Short Test of Spatial Memory with High Sensitivity for the Diagnosis of Pre-dementia Alzheimer&#039;s Disease

This article describes the 4 Mountains Test (4MT), a hippocampus-dependent test of working allocentric spatial memory. The hippocampus is affected early in Alzheimer's disease (AD) and this article outlines the 4MT methodology and results of patient testing, which demonstrates the value of the 4MT in the diagnosis of pre-dementia AD.

Den 4 Berg Test: ett kort test för fysisk minne med hög känslighet för diagnos av Pre-demens Alzheimers sjukdom

This protocol describes the administration of the 4 Mountains Test (4MT), a short test of spatial memory, in which memory for the topographical layout of ...

A Method to Test the Effect of Environmental Cues on Mating Behavior in Drosophila melanogaster

An individual's sexual drive is influenced by genotype, experience and environmental conditions. How these factors interact to modulate sexual behaviors remains poorly understood. In Drosophila melanogaster, environmental cues, such as food availability, affect mating activity offering a tractable system to investigate the mechanisms modulating sexual behavior. In D. melanogaster, environmental cues are often sensed via the chemosensory gustatory and olfactory systems. Here, we present a method to test the effect of environmental chemical cues on mating behavior. The assay consists of a small mating arena containing food medium and a mating couple. The mating frequency for each couple is continuously monitored for 24 h. Here we present the applicability of this assay to test environmental compounds from an external source through a pressurized air system as well as manipulation of the environmental components directly in the mating arena. The use of a pressurized air system is especially useful to test the effect of very volatile compounds, while manipulating components directly in the mating arena can be of value to ascertain a compound's presence. This assay can be adapted to answer questions about the influence of genetic and environmental cues on mating behavior and fecundity as well as other male and female reproductive behaviors.

A Method to Test the Effect of Environmental Cues on Mating Behavior in Drosophila melanogaster

We demonstrate an assay to analyze the environmental and genetic cues that influence mating behavior in the fruit fly Drosophila melanogaster.

En metod för att testa effekten av miljökanaler på parningsbeteende i<em&gt; Drosophila melanogaster</em

An individual's sexual drive is influenced by genotype, experience and environmental conditions. How these factors interact to modulate sexual behaviors ...

Novel Object Recognition Test for the Investigation of Learning and Memory in Mice

The object recognition test (ORT) is a commonly used behavioral assay for the investigation of various aspects of learning and memory in mice. The ORT is fairly simple and can be completed over 3 days: habituation day, training day, and testing day. During training, the mouse is allowed to explore 2 identical objects. On test day, one of the training objects is replaced with a novel object. Because mice have an innate preference for novelty, if the mouse recognizes the familiar object, it will spend most of its time at the novel object. Due to this innate preference, there is no need for positive or negative reinforcement or long training schedules. Additionally, the ORT can also be modified for numerous applications. The retention interval can be shortened to examine short-term memory, or lengthened to probe long-term memory. Pharmacological intervention can be used at various times prior to training, after training, or prior to recall to investigate different phases of learning (i.e., acquisition, early or late consolidation, or recall). Overall, the ORT is a relatively low-stress, efficient test for memory in mice, and is appropriate for the detection of neuropsychological changes following pharmacological, biological, or genetic manipulations.

The object recognition test (ORT) is a simple and efficient assay for evaluating learning and memory in mice. The methodology is described below.

Nya objekt erkännande Test för utredning av inlärning och minne hos möss

The object recognition test (ORT) is a commonly used behavioral assay for the investigation of various aspects of learning and memory in mice. The ORT is ...

Measuring Active and Passive Tameness Separately in Mice

Domesticated animals such as dogs and laboratory mice show a high level of tameness, which is important for humans to handle them easily. Tameness has two behavioral components: a reluctance to avoid humans (passive tameness) and a motivation to approach humans (active tameness). To quantify these components in mice, we previously developed behavioral tests for active tameness, passive tameness, and the willingness to stay on a human hand, each designed to be completed within 3 min. The data obtained were used for selective breeding, with a large number of mice analyzed per generation. The active tameness test measures the movement of the mouse toward a human hand and the contact it engages in. The passive tameness test measures the duration of time that a mouse tolerates human touch. In the stay-on-hand test, a mouse is placed on a human hand and touched slowly using the thumb of that hand; the duration of time that the animal remains on the hand is measured. Here, we describe the test set-up and apparatus, explain the procedures, and discuss the appropriate data analysis. Finally, we explain how to interpret the results.

Tameness in animals includes a reduction of avoidance responses to humans (passive tameness) and an increase in active approaches to humans (active tameness). Here, we describe detailed protocols for three behavioral tests (active tameness, passive tameness, and stay-on-hand tests) to separately measure the active and passive tameness of mice.

Mätning av aktiv och passiv tamhet separat hos möss

Domesticated animals such as dogs and laboratory mice show a high level of tameness, which is important for humans to handle them easily. Tameness has two ...