Name: behavioral assessment of manual dexterity in non-human primates
Uploaded: 2011-11-11T13:00:00
Duration: 16 min
Description: Watch this Scientific Journal Video about Behavioral Assessment of Manual Dexterity in Non-Human Primates at JoVE.com

המחברים מבקשים להודות פרופ &#39;שוואב ME, ד&quot;ר פ&#39; פרוינד, ד&quot;ר א Wyss, ד&quot;ר ס &#39;בשיר, ד&quot;ר א&#39; מיר, ד&quot;ר י בלוך, ד&quot;ר JF ברונה, ד&quot;ר ג&#39;יי Aebischer, ד&quot;ר א Meszaros, ד&quot;ר ו &#39;Goetschman על תרומתם ניסויים וניתוחים קודמים. הניסוי בחר קופצים נבנו על ידי אנדרה גיילרד, ברנרד Aebischer ולורן Monney. במתקן בעלי החיים, הקופים הושמו תחת פיקוח של מטפלים מקצועיים בעלי חיים: יוסף Corpataux, לורן שתלטנית ז&#39;אק מיילארד. בדיקות התנהגותיות ניתוח הנתונים, וכן היסטולוגיה, נערכו עם תרומות יקר מאוד של לבורנטים: ורוניק Moret (גם באינטרנט אב), פרנסואז Tinguely, כריסטין רולין, מוניקה Bennefeld, כריסטיאן Marti ו ג&#39;ורג&#39;ט פישר. עבודה זו נתמכה על ידי השוויצרי הקרן הלאומית למדע, מענקים לא 31-61857.00, 310000-110005, 31003A-132465 (EMR), 310,030-118,357, 31003A-104061 (TW), 310030-120,411 (ABS), PZ00P3_121646 (ES), נוברטיס קרן, המרכז הלאומי של יכולת מחקר (NCCR) על &quot;פלסטיות עצבית תיקון ו -&quot;.

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למרות משימות התנהגותיות הנוכחי נחשבו עד כה במעבדה שלנו בהקשר של מחקרים הקשורים הנגע של חוט צוואר הרחם או נגעים של הקורטקס המוטורי במטרה לבחון טיפולים שונים (ראה 14,15,17 ו <a href="http://www.unifr.ch/neuro/rouiller">http:/ / www.unifr.ch / נוירו / rouiller</a> &gt; בחר &quot;מחקר&quot; בתפריט בבר העליון, אז&gt; &quot;מנוע מערכת&quot;&gt; &quot;התאוששות לאחר פגיעה&quot;), הם עשויים להיות גם יישומים רחב, כמו מיומנות ידנית גם היבט לשקול פתולוגיות אחרות, כגון מחלת פרקינסון (קופים MPTP) או במקרה של הפרופריוספציה דה afferentation חושית להשפיע ו / או את חוש המישוש (במיוחד במבחן 2 בהעדר שליטה חזותית). בדיקות התנהגותיות המוצע כאן מתאים לחקור את השליטה המוטורית של תנועות הדיסטלי של forelimb, כפי מעורב מיומנות ידנית. הספציפיות של הבדיקות באה לידי ביטויהעדרו של הגירעון (למעט כמה ימים) במקרה של נגע אשר אינו פוגע המרכיבים הרלבנטיים של מערכת הבקרה: אכן, במקרה של נגע להציב הזנב יותר motoneurons השליטה שרירי היד, היה הגירעון לא. הרלוונטיות של מבחן 1 יכול להיות מוערך על ידי השוואת רצפי וידאו שצולמו בשתי נקודות זמן של עקומת שלאחר הנגע התאוששות, אשר שונה על ידי שיפור של התאוששות תפקודית של 25%, ואולי אף ביחס לטיפול תא טיפול 17. למרות בשלב מסוים, התחלתי הכשרה קצר יחסית בהתחלה (שנמשך בדרך כלל 2-3 חודשים), בדיקות התנהגותיות המוצעים כאן הם יחסית &quot;טבעי&quot; וישיר, לעומת (למשל מותנה) משימות מורכבות עבורו האימונים של הקוף עשוי להימשך כמעט שנה או יותר. חיזוק חיובי מבוססת על מזון מוצק, אשר רגיש פחות על נקודת מבט אתית יותר מאשר מחסור במים, משמש בדרך כלל com יותרPlex משימות 23. אין צורך לשלול את הקופים ממזון להשיג תוצאות יציבה ועקבית. כדורי שהתקבלו במהלך משימות מייצגים את הגישה הראשונה האוכל ביום הפגישה התנהגותיות (בהנחה הקוף לא אוכלת במהלך הלילה הקודם, אך מזון נוסף יכול להינתן עד סוף אחר הצהריים של היום הקודם) . זה חיוני כי כל קוף מבצעת את הפגישה התנהגותי באותו זמן של יום, כמו גם כיבוד בסדר רציף זהה בין קופים שונים ויצרו קבוצה בחדר הדיור. כמו הקופים רגישים לאירועים מטריד חיצוני, משימות התנהגותיות צריכה להתנהל בנוכחות של מוסיקת רקע, מיסוך הרעש המטריד הפוטנציאלי מגיע חדרים או במעבדות שכנות. זה חיוני כי במהלך כל תקופת הניסוי (מ ההכשרה הראשונית עד הפגישה האחרונה הניסוי מדי יום, תקופה של חודשים אם לא שנים מספר), קוף נתוןלהציב מדי יום תחת פיקוחו של הנסיין אותו. בדיקות התנהגותיות הנוכחי, משמש מאז כמה שנים במעבדה שלנו לכמת מיומנות ידנית, הם במידה מסוימת דומה בדיקות נוספות של מיומנות ידנית לאחרונה דווח בספרות 24-28. יש לעומת זאת צורך חיוני לתקנן בדיקות במעבדות ברחבי שונים (לצורך השוואה טובה יותר), המהווה יעד סופי של הדו&quot;ח הנוכחי. על פי דרישה, את המאפיינים מפורט של מערכת קופצים מאויר כאן לבדיקות 1-4 יכול להיות מסופק על ידי המחבר המתאים, כדי לשכפל אותם. מעבר לנושא של רפואה רגנרטיבית (ההתאוששות מן הנגע של חוט השדרה או קליפת המוח), בלוח הנוכחי של המבחנים עשוי להיות מתאים כתובת אי - אדם נורמלי פרימטים בעיות התפתחותיות (למשל כמובן זמן של התפתחות מוטורית של תנועות מיומנות), כדי לחקור lateralization היבטים (יד העדפה / דומיננטיות) ו לשאלות לפענח אבולוציוני על ידי גomparing את יכולות המנוע של מינים שונים של פרימטים, כולל בבני אדם. הערה זאת כי ממדי מנגנוני צריך להיות מותאם לפי גודל &quot;ספרות (עובי ואורך) של מין הפרימטים, מכיוון שהוא עלול להשפיע על ביצועי המשימות. במחקר הנוכחי, הבדיקות נערכו על קופים macaca fascicularis, החל 2.5-8 שנים ומשקלו בין 2.5 ו - 8 ק&quot;ג. אורך האצבע המורה (בשימוש לראשונה כדי לתפעל את כדורי) נע בין 32 ל 35 מ&quot;מ, ואילו היקף הפלנקס הדיסטלי (טיפ) של האצבע המורה היה בין 22 ו 25 מ&quot;מ הקופים כלל במחקרים שלנו. נבדק כמו בניסויים קודמים, בדיקות לתפוס אותו מתאימים macaca המולאטית גם כן. כל הניסויים נערכו בהתאם מדריך לטיפול ושימוש בחיות מעבדה (1996) ואושרה על ידי (שוויץ), הרשויות המקומיות וטרינרי. כל הפרוצדורות על הקוףים, כמו גם את תנאי המעצר במתקן בעלי חיים, תוארו בהרחבה בדו&quot;חות האחרונים מהמעבדה שלנו: לראות הפניות 12-18.

behavioral assessment of manual dexterity in non-human primates

בדרכי (CS) corticospinal היא תמיכה אנטומי של יכולת מוטורית מעולה במיומנות כדי לתפעל אובייקטים קטנים, בעיקר זכותו של פרימטים 1. במקרה של פגיעה המשפיעות על מערכת הקרנה CS על מקורו (הנגע של אזורים בקליפת המוח המוטורית) או לאורך מסלולו (פגיעה בחוט צוואר הרחם), קיים הפסד דרמטי של מיומנות ידנית (שיתוק ביד), כפי שראינו אצל חלק מהחולים tetraplegic או משותק ומחוסר . למרות שיש התאוששות ספונטנית לאחר פגיעה תפקודית כזה, הוא נותר מוגבל מאוד מבוגר. אסטרטגיות טיפוליות שונים מוצעים כיום (טיפול בתא למשל, נטרול מולקולות מעכבות צמיחה axonal, היישום של גורמי גדילה, וכו &#39;), אשר מפותחים בעיקר מכרסמים. עם זאת, לפני יישום קליני, מומלץ לעתים קרובות כדי לבדוק את הכדאיות, היעילות והביטחון של הטיפול ב פרימטים שאינם בני אדם. הדבר נכון במיוחד כאשר המטרה היא לשחזר מיומנות ידנית לאחרפגיעה של מערכת העצבים המרכזית, כמו הארגון של מערכת התנועה של מכרסמים שונה מזו של פרימטים 1,2. קופי מקוק מומחשים כאן כמודל התנהגותי מתאים לכמת מיומנות ידנית אצל הפרימטים, כדי לשקף את הגירעונות הנובעים הנגע של הקורטקס המוטורי או בחוט צוואר הרחם למשל, למדוד את מידת ההחלמה התפקודית ספונטנית, כאשר הטיפול מיושם, להעריך כמה זה יכול לשפר את ההחלמה התפקודית. ההערכה ההתנהגותית של מיומנות ידנית מבוססת על ארבע ברורים, משלימים משימות להגיע ולתפוס ידנית (שימוש אחיזה דיוק לתפוס כדורי), הדורשים הכשרה ראשונית של קופי מקוק מבוגר. הכנה של בעלי החיים הוא הוכיח, כמו גם המיצוב ביחס התנהגותיים הגדרת. המופע של קוף טיפוסי מודגמת עבור כל משימה. איסוף וניתוח של הפרמטרים הרלוונטיים המשקף manipula יד מדויקתtion, כמו גם את השליטה על כוח, הם הסבירו והדגימו עם תוצאות נציג. נתונים אלה ממוקמים אז בהקשר רחב יותר, מראה כיצד נתונים התנהגותיים ניתן לנצל כדי לחקור את ההשפעה של פגיעה בחוט השדרה או של נגע של הקורטקס המוטורי ועד כמה הטיפול יכול לשפר את תפקודי התאוששות ספונטנית, על ידי השוואת קבוצות שונות של קופים (טיפול דמה לעומת מטופלים למשל). יתרונות ומגבלות של בדיקות התנהגותיות הם דנו. הגישה ההתנהגותית הנוכחי עולה בקנה אחד עם דיווחים קודמים תוך שימת דגש על הרלוונטיות של המודל הלא האדם הפרימטים בהקשר של מחלות מערכת העצבים 2,3.

Watch this Scientific Journal Video about Behavioral Assessment of Manual Dexterity in Non-Human Primates at JoVE.com

Behavioral Assessment of Manual Dexterity in Non-Human Primates

כפי מיומנות ידנית היא בעיקר זכותו של פרימטים, משימות התנהגותיות פותחו קופי מקוק. ארבעה להגיע ולתפוס משימות prehension, מדידה מניפולציה מצד היכולת והכוח, לאפשר להקים התאוששות לאחר פגיעה תפקודית של מערכת העצבים המרכזית ועל מנת לבחון את ההשפעה של הטיפול.

הערכה התנהגותית של מיומנות ידני יונקים לא אנושיים

The corticospinal (CS) tract is the anatomical support of the exquisite motor ability to skillfully manipulate small objects, a prerogative mainly of ...

behavioral-assessment-of-manual-dexterity-in-non-human-primates

Research

JoVE Journal

Neuroscience

A General Method for Evaluating Incubation of Sucrose Craving in Rats

For someone on a food-restricted diet, food craving in response to food-paired cues may serve as a key behavioral transition point between abstinence and relapse to food taking 1. Food craving conceptualized in this way is akin to drug craving in response to drug-paired cues. A rich literature has been developed around understanding the behavioral and neurobiological determinants of drug craving; we and others have been focusing recently on translating techniques from basic addiction research to better understand addiction-like behaviors related to food 2-4.
As done in previous studies of drug craving, we examine sucrose craving behavior by utilizing a rat model of relapse. In this model, rats self-administer either drug or food in sessions over several days. In a session, lever responding delivers the reward along with a tone+light stimulus. Craving behavior is then operationally defined as responding in a subsequent session where the reward is not available. Rats will reliably respond for the tone+light stimulus, likely due to its acquired conditioned reinforcing properties 5. This behavior is sometimes referred to as sucrose seeking or cue reactivity. In the present discussion we will use the term "sucrose craving" to subsume both of these constructs.
In the past decade, we have focused on how the length of time following reward self-administration influences reward craving. Interestingly, rats increase responding for the reward-paired cue over the course of several weeks of a period of forced-abstinence. This "incubation of craving" is observed in rats that have self-administered either food or drugs of abuse 4,6. This time-dependent increase in craving we have identified in the animal model may have great potential relevance to human drug and food addiction behaviors.
Here we present a protocol for assessing incubation of sucrose craving in rats. Variants of the procedure will be indicated where craving is assessed as responding for a discrete sucrose-paired cue following extinction of lever pressing within the sucrose self-administration context (Extinction without cues) or as responding for sucrose-paired cues in a general extinction context (Extinction with cues).

Responding for food or drug-paired cues increases over the course of a period of abstinence and this may relate to an increased susceptibility to relapse behaviors. Here we detail a procedure for evaluating this "incubation of craving" in rats that have self-administered sucrose.

שיטה כללית להערכת דגירה של השתוקקות סוכרוז בחולדות

For someone on a food-restricted diet, food craving in response to food-paired cues may serve as a key behavioral transition point between abstinence and ...

Recording and Analysis of Circadian Rhythms in Running-wheel Activity in Rodents

When rodents have free access to a running wheel in their home cage, voluntary use of this wheel will depend on the time of day1-5. Nocturnal rodents, including rats, hamsters, and mice, are active during the night and relatively inactive during the day. Many other behavioral and physiological measures also exhibit daily rhythms, but in rodents, running-wheel activity serves as a particularly reliable and convenient measure of the output of the master circadian clock, the suprachiasmatic nucleus (SCN) of the hypothalamus. In general, through a process called entrainment, the daily pattern of running-wheel activity will naturally align with the environmental light-dark cycle (LD cycle; e.g. 12 hr-light:12 hr-dark). However circadian rhythms are endogenously generated patterns in behavior that exhibit a ~24 hr period, and persist in constant darkness. Thus, in the absence of an LD cycle, the recording and analysis of running-wheel activity can be used to determine the subjective time-of-day. Because these rhythms are directed by the circadian clock the subjective time-of-day is referred to as the circadian time (CT). In contrast, when an LD cycle is present, the time-of-day that is determined by the environmental LD cycle is called the zeitgeber time (ZT).
Although circadian rhythms in running-wheel activity are typically linked to the SCN clock6-8, circadian oscillators in many other regions of the brain and body9-14 could also be involved in the regulation of daily activity rhythms. For instance, daily rhythms in food-anticipatory activity do not require the SCN15,16 and instead, are correlated with changes in the activity of extra-SCN oscillators17-20. Thus, running-wheel activity recordings can provide important behavioral information not only about the output of the master SCN clock, but also on the activity of extra-SCN oscillators. Below we describe the equipment and methods used to record, analyze and display circadian locomotor activity rhythms in laboratory rodents.

Circadian rhythms in voluntary wheel-running activity in mammals are tightly coupled to the molecular oscillations of a master clock in the brain. As such, these daily rhythms in behavior can be used to study the influence of genetic, pharmacological, and environmental factors on the functioning of this circadian clock.

הקלטה וניתוח של מקצבי יממה בריצת גלגל פעילות במכרסמים

When rodents have free access to a running wheel in their home cage, voluntary use of this wheel will depend on the time of day1-5. Nocturnal rodents, ...

Assessment of Dendritic Arborization in the Dentate Gyrus of the Hippocampal Region in Mice

Dendritic arborization has been shown to be a reliable marker for examination of structural and functional integrity of neurons. Indeed, the complexity and extent of dendritic arborization correlates well with the synaptic plasticity in these cells. A reliable method for assessment of dendritic arborization is needed to characterize the deleterious effects of neurological disorders on these structures and to determine the effects of therapeutic interventions. However, quantification of these structures has proven to be a formidable task given their complex and dynamic nature. Fortunately, sophisticated imaging techniques can be paired with conventional staining methods to assess the state of dendritic arborization, providing a more reliable and expeditious means of assessment. Below is an example of how these imaging techniques were paired with staining methods to characterize the dendritic arborization in wild type mice. These complementary imaging methods can be used to qualitatively and quantitatively assess dendritic arborization that span a rather wide area within the hippocampal region.

We describe two methods for visualization and quantification of dendritic arborization in the hippocampus of mouse models: real-time and extended depth of field imaging. While the former method allows sophisticated topographical tracing and quantification of the extent of branching, the latter allows speedy visualization of the dendritic tree.

הערכה של דנדריטים arborization ברכס המשונן של האזור בהיפוקמפוס של עכברים

Dendritic arborization has been shown to be a reliable marker for examination of structural and functional integrity of neurons. Indeed, the complexity ...

Quantification of Filamentous Actin (F-actin) Puncta in Rat Cortical Neurons

Filamentous actin protein (F-actin) plays a major role in spinogenesis, synaptic plasticity, and synaptic stability. Changes in dendritic F-actin rich structures suggest alterations in synaptic integrity and connectivity. Here we provide a detailed protocol for culturing primary rat cortical neurons, Phalloidin staining for F-actin puncta, and subsequent quantification techniques. First, the frontal cortex of E18 rat embryos are dissociated into low-density cell culture, then the neurons grown in vitro for at least 12-14 days. Following experimental treatment, the cortical neurons are stained with AlexaFluor 488 Phalloidin (to label the dendritic F-actin puncta) and microtubule-associated protein 2 (MAP2; to validate the neuronal cells and dendritic integrity). Finally, specialized software is used to analyze and quantify randomly selected neuronal dendrites. F-actin rich structures are identified on second order dendritic branches (length range 25-75 &#181;m) with continuous MAP2 immunofluorescence. The protocol presented here will be a useful method for investigating changes in dendritic synapse structures subsequent to experimental treatments.

Quantification of Filamentous Actin F-actin Puncta in Rat Cortical Neurons

Filamentous actin (F-actin) plays an important role in spinogenesis, synaptic plasticity, and synaptic stability. Quantification of F-actin puncta is therefore a useful tool to study the integrity of synaptic structures. This protocol describes the procedures of quantifying F-actin puncta labeled with Phalloidin in low-density primary cortical neuronal cultures.

כימות פילמנטיות אקטין (F- אקטין) puncta ב עכברוש נוירונים קליפתיים

Filamentous actin protein (F-actin) plays a major role in spinogenesis, synaptic plasticity, and synaptic stability. Changes in dendritic F-actin rich ...

Identification of Dopamine D1-Alpha Receptor Within Rodent Nucleus Accumbens by an Innovative RNA In Situ Detection Technology

In the central nervous system, the D1-alpha subtype receptor (Drd1&#945;) is the most abundant dopamine (DA) receptor, which plays a vital role in regulating neuronal growth and development. However, the mechanisms underlying Drd1&#945; receptor abnormalities mediating behavioral responses and modulating working memory function are still unclear. Using a novel RNA in situ hybridization assay, the current study identified dopamine Drd1&#945; receptor and tyrosine hydroxylase (TH) RNA expression from DA-related circuitry in the nucleus accumbens (NAc) area and substantia nigra region (SNR), respectively. Drd1&#945; expression in the NAc shows a &#34;discrete dot&#34; staining pattern. Clear sex differences in Drd1&#945; expression were observed. In contrast, TH shows a &#34;clustered&#34; staining pattern. Regarding TH expression, female rats displayed a higher signal expression per cell relative to male animals. The methods presented here provide a novel in situ hybridization technique for investigating changes in dopamine system dysfunction during the progression of central nervous system diseases.

Identification of Dopamine D1-Alpha Receptor Within Rodent Nucleus Accumbens by an Innovative RNA In Situ Detection Technology

Identification of dopamine D1-alpha receptor in the nucleus accumbens is critical for clarifying D1 receptor dysfunction during a central nervous system disease. We performed a novel RNA in situ hybridization assay to visualize single RNA molecules in a specific brain area.

זיהוי של דופמין קולטן D1-אלפא בתוך מכרסמים גרעין האקומבנס על ידי טכנולוגיה חדשנית RNA בחיי עיר זיהוי

In the central nervous system, the D1-alpha subtype receptor (Drd1&#945;) is the most abundant dopamine (DA) receptor, which plays a vital role in ...

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

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

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

הכוח של מרווח Interstimulus להערכה של זמני עיבוד בחולדות

Temporal processing deficits have been implicated as a potential elemental dimension of higher-level cognitive processes, commonly observed in ...

Assessment of Long-term Depression Induction in Adult Cerebellar Slices

Synaptic plasticity provides a mechanism for learning and memory. For cerebellar motor learning, long-term depression (LTD) of synaptic transmissions from parallel fibers (PF) to Purkinje cells (PC) is considered the basis for motor learning, and deficiencies of both LTD and motor learning are observed in various gene-manipulated animals. Common motor learning sets, such as adaptation of the optokinetic reflex (OKR), the vestibular-ocular reflex (VOR), and rotarod test were used for evaluation of motor learning ability. However, results obtained from the GluA2-carboxy terminus modified knock-in mice demonstrated normal adaptation of the VOR and the OKR, despite lacking PF-LTD. In that report, induction of LTD was only attempted using one type of stimulation protocol at room temperature. Thus, conditions to induce cerebellar LTD were explored in the same knock-in mutants using various protocols at near physiological temperature. Finally, we found stimulation protocols, by which LTD could be induced in these gene-manipulated mice. In this study, a set of protocols are proposed to evaluate LTD-induction, which will more accurately allow examination of the causal relationship between LTD and motor learning. In conclusion, experimental conditions are crucial when evaluating LTD in gene-manipulated mice.

In some gene-manipulated animals, using a single protocol may fail to induce LTD in cerebellar Purkinje cells, and there may be a discrepancy between LTD and motor learning. Multiple protocols are necessary to assess LTD-induction in gene-manipulated animals. Standard protocols are shown.

הערכה של האינדוקציה לטווח ארוך של דיכאון פרוסות למבוגרים בלבד

Synaptic plasticity provides a mechanism for learning and memory. For cerebellar motor learning, long-term depression (LTD) of synaptic transmissions from ...

Ballistic Labeling of Pyramidal Neurons in Brain Slices and in Primary Cell Culture

It has been reported that the size and shape of dendritic spines is related to their structural plasticity. To identify the morphological structure of pyramidal neurons and dendritic spines, a ballistic labeling technique can be utilized. In the present protocol, pyramidal neurons are labeled with DilC18(3) dye and analyzed using neuronal reconstruction software to assess neuronal morphology and dendritic spines. To investigate neuronal structure, dendritic branching analysis and Sholl analysis are performed, allowing researchers to draw inferences about dendritic branching complexity and neuronal arbor complexity, respectively. The evaluation of dendritic spines is conducted using an automatic assisted classification algorithm integral to the reconstruction software, which classifies spines into four categories (i.e., thin, mushroom, stubby, filopodia). Furthermore, an additional three parameters (i.e., length, head diameter, and volume) are also chosen to assess alterations in dendritic spine morphology. To validate the potential of wide application of the ballistic labeling technique, pyramidal neurons from in vitro cell culture were successfully labeled. Overall, the ballistic labeling method is unique and useful for visualizing neurons in different brain regions in rats, which in combination with sophisticated reconstruction software, allows researchers to elucidate the possible mechanisms underlying neurocognitive dysfunction.

We present a protocol to label and analyze pyramidal neurons, which is critical for evaluating potential morphological alterations in neurons and dendritic spines that may underlie neurochemical and behavioral abnormalities.

בליסטי לתיוג של הנוירונים בתוך המוח בפרוסות ובתרבות התא הראשוני

It has been reported that the size and shape of dendritic spines is related to their structural plasticity. To identify the morphological structure of ...

A Hydrophobic Tissue Clearing Method for Rat Brain Tissue

Hydrophobic tissue clearing methods are easily adjustable, fast, and low-cost procedures that allows for the study of a molecule of interest in unaltered tissue samples. Traditional immunolabeling procedures require cutting the sample into thin sections, which restricts the ability to label and examine intact structures. However, if brain tissue can remain intact during processing, structures and circuits can remain intact for the analysis. Previously established clearing methods take significant time to completely clear the tissue, and the harsh chemicals can often damage sensitive antibodies. The iDISCO method quickly and completely clears tissue, is compatible with many antibodies, and requires no special lab equipment. This technique was initially validated for the use in mice tissue, but the current protocol adapts this method to image hemispheres of control and transgenic rat brains. In addition to this, the present protocol also makes several adjustments to preexisting protocol to provide clearer images with less background staining. Antibodies for Iba-1 and tyrosine hydroxylase were validated in the HIV-1 transgenic rat and in F344/N control rats using the present hydrophobic tissue clearing method. The brain is an interwoven network, where structures work together more often than separately of one another. Analyzing the brain as a whole system as opposed to a combination of individual pieces is the greatest benefit of this whole brain clearing method.

Here we present a hydrophobic tissue clearing method that allows for the viewing of target molecules as part of intact brain structures. This technique has now been validated for F344/N control and HIV-1 transgenic rats of both sexes.

שיטת ניקוי רקמות הידרופובית לרקמת מוח חולדה

Hydrophobic tissue clearing methods are easily adjustable, fast, and low-cost procedures that allows for the study of a molecule of interest in unaltered ...

A Rat Model of EcoHIV Brain Infection

It has been well studied that the EcoHIV infected mouse model is of significant utility in investigating HIV associated neurological complications. Establishment of the EcoHIV infected rat model for studies of drug abuse and neurocognitive disorders, would be beneficial in the study of neuroHIV and HIV-1 associated neurocognitive disorders (HAND). In the present study, we demonstrate the successful creation of a rat model of active HIV infection using chimeric HIV (EcoHIV). First, the lentiviral construct of EcoHIV was packaged in cultured 293 FT cells for 48 hours. Then, the conditional medium was concentrated and titered. Next, we performed bilateral stereotaxic injections of the EcoHIV-EGFP into F344/N rat brain tissue. One week after infection, EGFP fluorescence signals were detected in the infected brain tissue, indicating that EcoHIV successfully induces an active HIV infection in rats. In addition, immunostaining for the microglial cell marker, Iba1, was performed. The results indicated that microglia were the predominant cell type harboring EcoHIV. Furthermore, EcoHIV rats exhibited alterations in temporal processing, a potential underlying neurobehavioral mechanism of HAND as well as synaptic dysfunction eight weeks after infection. Collectively, the present study extends the EcoHIV model of HIV-1 infection to the rat offering a valuable biological system to study HIV-1 viral reservoirs in the brain as well as HAND and associated comorbidities such as drug abuse.

Here, we present a protocol to establish a new rat model of active HIV infection using chimeric HIV (EcoHIV), which is critical for enhancing our understanding of HIV-1 viral reservoirs in the brain and offering a system to study HIV-associated neurocognitive disorders and associated comorbidities (i.e., drug abuse).

מודל עכברוש של זיהום מוחי EcoHIV

It has been well studied that the EcoHIV infected mouse model is of significant utility in investigating HIV associated neurological complications. ...