金融衍生工具是支持由美国国家精神分裂症和抑郁症研究联盟和俄共从加拿大精神病学研究基金会奖的青年研究者奖。

一，任务设计，刺激，实验协议<ol><li>此协议的基本任务是一个延迟响应WM的任务，新任务无关的情绪和中性分心之间的备忘录和探头（见图1图说明原来的任务）的延迟间隔期间。事件相关的fMRI数据记录，而参与者执行此任务。作为感性的控制，具有相同的基本属性（例如，空间频率和亮度），也可以用来炒的实际分心版本。 </li></ol><img src="/files/ftp_upload/2434/2434fig1.jpg" alt="图1" /> 图1。总图的延迟响应工作记忆任务与牵引 （6日 ，经许可）。三面在备忘录，以强烈的参与背的行政系统，和对小说分心用于以增加IMPACWM性能和大脑活动的情感分心吨。情感分心的影响，也可以增加呈现彩色照片（未显示），并通过配对类似的情感和语义内容分心。在这种情况下，小心应重视，也符合基本属性，如亮度和空间频率 15，情绪和中性图片，以避免可能的混淆。与会者指示保持其对WM任务的重点，而仍在处理中的分心，并按下响应按钮（1 = 2，旧=新）探针快速而准确的答复。对于刺激呈现，我们使用CIGAL（ <a href="http://www.nitrc.org/projects/cigal/">http://www.nitrc.org/projects/cigal/</a> ）。备忘录和探头可呈现在彩色或黑白。 <ol start="2"><li>这是建议在备忘录的面孔的性别平衡的男性比例（50％）和Females（50％）。类似的平衡的比例也建议为老（50％） 和新（50％）探针。通过改变这些比例和/或不同的其他因素 - 例如，从相同的备忘录和他们的相似性与探针和/或存在/不存在通过操纵面之间的面部特征的相似性，可以是多种多样的WM任务的难度额外的面部特征，在备忘录（见影片）。除了 ​​到面，也可以用于其他刺激如备忘录和探头9。 </li><li>建议每30-40试验条件6，11用于这种设计，虽然其作为一个"慢节奏"设计强大的fMRI信号的稳定，也可以用较少的试验获得（见补充材料从6 ）。这允许〜1.5-2小时fMRI数据的收集，这是可行的健康和临床的参与者使用的。尽管其轻微的缺点，由于相对较低的试验可以参与"快节奏"的设计相比，这种设计已获得更稳定的审单的fMRI信号，并更好地与个别试验相关的信号分离试验刺激/阶段内的优势和功能，这也是有利连通性分析。 </li><li>分心类型的变化，也有助于这种设计的多功能性，根据调查和目标人群的目标适应。 6在原设计的情感和中性分心是从国际情感图片系统 16，但类似的效果可与其他新的刺激是有效的分心 12，和/或操作，增加的WM任务的敏感性检测行为上的差异（例如，通过评估参与者的信心，他们的反应）11。 </li><li>例如，在最近的一项研究在战后已经有或无创伤后应激障碍（PTSD）12 terans，情感IAPS图片诱导一般负面情绪与战斗有关的图片取代。诱发情绪，更具体的联系，以打击有关的创伤，从而更有效地打击暴露的同伙分心，特别是在创伤后应激障碍组，预计这些照片。此外，刺激，诱导特异性的负面情绪（如焦虑）或情绪积极的刺激也可能是因为分心使用。举例来说，面临着显示可怕的表达式可能会引起社会焦虑，从而有效地调查的瞬态诱发焦虑分心的影响在WM 11。此外，类似的效果，可以发现 17个积极的分心。 </li><li>最后，联同其他措施（例如，行为和个性有关）这个范式也可以用来研究大脑活动和个人之间的关系不同<html> ences在这个任务8，10，11，影响认知能力的各个方面。 </li></ol>二。准备扫描的主题所有参加者须提供书面知情同意书之前，运行实验的协议，这应该是一个伦理委员会批准。 在进入扫描室<ol><li>在一天的扫描，目前参与者的情感状态进行评估，控制的心情与分心西医任务的影响。与扫描后评估，初步评估也可用于情绪的变化，以屏幕作为参与这项研究11的结果。 </li><li>扫描之前，参与者被告知详细的扫描程序，是行为的工作给予了具体的指示。与会者还完成了一个简短的练习，熟悉任务。 </li></ol>e_step"&gt;进入扫描室<ol start="3"><li>参与者仰卧扫描床，额外的缓冲头，以确保在扫描过程中的舒适性，并尽量减少运动。为了进一步减少头部运动，非粘合面的磁带的长度可围绕这一主题的额头轻轻包裹。科目耳保护以及隔离耳机与沟通在MRI扫描实验者。 </li><li>主题的右手响应中的定位舒适。开始收集数据之前，关键是确保响应按钮的正常工作，主体可以看到刺激呈现屏幕投影明确。紧急停止按钮也置于附近，使这个问题可能表明任何迫切需要停止扫描仪。 </li></ol>扫描会话<ol start="5"><li>额外的任务，可用于进一步的行为assessmenTS - 例如，以确定参与者的评级灵敏度的分心，分心和/或主观感知的分心分心的情感价/强度。可以使用这些评级，以确保在扫描过程中使用的情绪刺激的主观感知，复制以前在文学的影响，并在收视率的个体差异，可用于调查调解认知6情感的不利影响的神经机制影响8。 </li><li>人格特质（例如，特质焦虑，情绪反应）的评估，也可以进行MRI扫描后，如果不执行扫描前11。 </li></ol>三。数据记录和分析扫描参数 6在原有的研究，我们使用核磁共振录音4特斯拉的通用电气扫描器收集的MRI资料，但更多RECENT版本的任务，我们还成功地MRI数据收集与1.5 T 扫描仪11。 4T扫描仪，30个功能片系列（体素大小= 4 × 4 × 4毫米）收购轴向使用逆螺旋脉冲序列（TR = 2000 ms时，TE = 31毫秒;领域的角度= 256 ×256毫米） ，从而使覆盖全脑。同样，在1.5扫描仪，28个功能片系列（体素大小= 4 × 4 × 4毫米），获得轴向使用echoplanar序列（TR = 2000 ms时，TE = 40毫秒;查看= 256 × 256毫米领域）。高分辨率结构图像，还获得了在轴向方向（平面分辨率= 1毫米2;解剖功能比= 4:1）。 数据分析我们使用统计参数图（SPM: <a href="http://www.fil.ion.ucl.ac.uk/spm/">http://www.fil.ion.ucl.ac.uk/spm/</a> ）与内部基于Matlab工具组合。前处理涉及的典型步骤:质量保证，TR一个lignment，修正的议案，共同登记，正常化，和平滑（使用8 × 8 × 8 mm内核）; *基本的质量保证数据的视觉检验，检测的参与者和运动有关的文物，在总变动数据，以及作为确定MR信号的不寻常尖峰卷。根据分心类型（情感与中性分心），个人和组级统计分析涉及的大脑活动进行比较。此外，脑成像数据与主观或客观的措施，注意力不集中（例如，情绪和注意力不集中的收视率和工作内存性能）6,8,11和/或分数索引的个性措施的相关性（ 例如 ，特质焦虑） 11也可以进行，调查大脑活动的合作随着这些措施的个体差异。在所有使用此协议，我们的研究分析通常集中在延迟间隔，WHE观察活动n的分心，但活动时间锁定到其他事件（如探测器）也可以进行调查。 四。代表性的成果<img src="/files/ftp_upload/2434/2434fig2.jpg" alt="图2" /> 图2。相反的模式活动中存在的情感牵引 （6日 ，经许可） 在腹与背脑神经系统 。情绪分心生产，如腹外侧前额叶皮层（vlPFC）和杏仁核（未显示），腹侧情感的大脑区域（红色斑点）活性增强，同时产生如背外侧前额叶皮层，背执行的大脑区域（蓝色斑点）活性下降（dlPFC）和外侧顶叶皮层（LPC）。中央图像显示激活的地图至少分心条件与大多数（即情感与炒）之间的直接对比，横向显示的高分辨率的脑图像上叠加查看右半球。在脑图像的底部颜色横条显示激活地图的 t值的梯度。线图显示，在具有代表性的背，腹的大脑区域（颜色编码的箭头表示）的活动时间课程。 x轴以上的灰色矩形框表示备忘录的发作和持续时间，分心，和探针，分别。护卫舰=梭状回。

<ol>
	<li>Dolcos, F., Iordan, A. D., Dolcos, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Neural+correlates+of+emotion-cognition+interactions:+A+review+of+evidence+from+brain+imaging+investigations.">Neural correlates of emotion-cognition interactions: A review of evidence from brain imaging investigations.</a> J. Cogn. Psychol. 23, 669-694 (2011).</li><li>Shafer, A., Iordan, A., Cabeza, R., Dolcos, F. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Brain+imaging+investigation+of+the+memory-enhancing+effect+of+emotion.">Brain imaging investigation of the memory-enhancing effect of emotion.</a> J. Vis. Exp. (51), (2011).</li><li>Dolcos, F., LaBar, K. S., Cabeza, R., Uttl, B., Ohta, N., Siegenthaler, A. 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Y. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Stress+shifts+brain+activation+towards+ventral+'affective'+areas+during+emotional+distraction.">Stress shifts brain activation towards ventral 'affective' areas during emotional distraction.</a> Soc. Cogn. Affect. Neurosci. [Epub ahead of. , (2011).</li><li>Dolcos, F., Miller, B., Kragel, P., Jha, A., McCarthy, G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Regional+brain+differences+in+the+effect+of+distraction+during+the+delay+interval+of+a+working+memory+task.">Regional brain differences in the effect of distraction during the delay interval of a working memory task.</a> Brain Res. 1152, 171-181 (2007).</li><li>Morey, R. 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没有利益冲突的声明。

这个实验设计提供了最初的脑成像的证据表明，对正在进行的认知过程，情感分心的不利影响带来HotEmo腹侧神经系统和ColdEx背系统之间的相互调制。这种背腹的分解与西医受损表现在情感分心 6的存在，一直在正常8-11，12-14临床系统复制，并改变其他条件，如睡眠剥夺10和18压力。更重要的是，它也证明是特定的情绪，正面和负面的 17?...

brain imaging investigation of the impairing effect of emotion on cognition

情绪可以影响施加既提高 （例如，更好地为情绪事件的记忆 ），损害（例如，增加情感分心） 的影响（1审查）的认知。补充我们最近的协议 2描述的方法，让情感的记忆增强作用（ 见1，3-5）的神经关联的调查，在这里我们提出了一个协议，允许调查的不利影响神经关联情感对认知。这种方法的主要特点是，它允许之间的互惠调制腹侧神经系统活动的参与，参与更高层次的"冷""热"情绪加工 （HotEmo系统），和背侧系统的鉴定认知/行政处理（ColdEx系统），这是与认知表现和个人行为的变化（1审查） 。由于其初始introduction 6已经证明，这种设计在澄清关于对认知的情感分心造成的不利影响神经关联的各方面，特别是通用和有影响力的的，与工作记忆（WM）为重点， 并由此应对7,11 ，既健康8-11和临床参与者12-14。

Watch this Scientific Journal Video about Brain Imaging Investigation of the Impairing Effect of Emotion on Cognition at JoVE.com

Brain Imaging Investigation of the Impairing Effect of Emotion on Cognition

我们提出了一个协议，允许调解的情感对认知的不利影响，使用功能磁共振成像的神经机制的调查。该协议可用于健康和临床的参与者。

脑成像的情感对认知损害的影响调查

Emotions can impact cognition by exerting both enhancing (e.g., better memory for emotional events) and impairing (e.g., increased emotional ...

brain-imaging-investigation-impairing-effect-emotion-on

Universidad de Cartagena UDEC

Research

JoVE Journal

Neuroscience

16.0K 次观看.  University of Alberta. 我们提出了一个协议，允许调解的情感对认知的不利影响，使用功能磁共振成像的神经机制的调查。该协议可用于健康和临床的参与者。

视频: Brain Imaging Investigation of the Impairing Effect of Emotion on Cognition

State-Dependency Effects on TMS:  A Look at Motive Phosphene Behavior

Transcranial magnetic stimulation (TMS) is a non-invasive neurostimulatory and neuromodulatory technique that can transiently or lastingly modulate cortical excitability (either increasing or decreasing it) via the application of localized magnetic field pulses.1,2 Within the field of TMS, the term state dependency refers to the initial, baseline condition of the particular neural region targeted for stimulation. As can be inferred, the effects of TMS can (and do) vary according to this primary susceptibility and responsiveness of the targeted cortical area.3,4,5

In this experiment, we will examine this concept of state dependency through the elicitation and subjective experience of motive phosphenes. Phosphenes are visually perceived flashes of small lights triggered by electromagnetic pulses to the visual cortex. These small lights can assume varied characteristics depending upon which type of visual cortex is being stimulated. In this particular study, we will be targeting motive phosphenes as elicited through the stimulation of V1/V2 and the V5/MT+ complex visual regions.6

In this article, we examine the effects of visually relevant state dependency on TMS induced motive phosphenic presentations.

依赖国家对TMS的:一看动机幻视行为

Transcranial magnetic stimulation (TMS) is a non-invasive neurostimulatory and neuromodulatory technique that can transiently or lastingly modulate ...

科研

神经科学

Brain Imaging Investigation of the Neural Correlates of Observing Virtual Social Interactions

The ability to gauge social interactions is crucial in the assessment of others&#x2019; intentions. Factors such as facial expressions and body language affect our decisions in personal and professional life alike 1. These "friend or foe" judgements are often based on first impressions, which in turn may affect our decisions to "approach or avoid". Previous studies investigating the neural correlates of social cognition tended to use static facial stimuli 2. Here, we illustrate an experimental design in which whole-body animated characters were used in conjunction with functional magnetic resonance imaging (fMRI) recordings. Fifteen participants were presented with short movie-clips of guest-host interactions in a business setting, while fMRI data were recorded; at the end of each movie, participants also provided ratings of the host behaviour. This design mimics more closely real-life situations, and hence may contribute to better understanding of the neural mechanisms of social interactions in healthy behaviour, and to gaining insight into possible causes of deficits in social behaviour in such clinical conditions as social anxiety and autism 3.

This article demonstrates an experimental design in which whole-body animated characters are used in conjunction with functional magnetic resonance imaging (fMRI) to investigate the neural correlates of observing virtual social interactions.

观察虚拟社会交往中的神经关联的脑成像研究

The ability to gauge social interactions is crucial in the assessment of others&#x2019; intentions. Factors such as facial expressions and body language ...

Brain Imaging Investigation of the Neural Correlates of Emotional Autobiographical Recollection

Recollection of emotional autobiographical memories (AMs) is important to healthy cognitive and affective functioning 1 - remembering positive AMs is associated with increased personal well-being and self-esteem 2, whereas remembering and ruminating on negative AMs may lead to affective disorders 3. Although significant progress has been made in understanding the brain mechanisms underlying AM retrieval in general (reviewed in 4, 5), less is known about the effect of emotion on the subjective re-experience of AMs and the associated neural correlates. This is in part due to the fact that, unlike the investigations of the emotion effect on memory for laboratory-based microevents (reviewed in 6, 7-9), often times AM studies do not have a clear focus on the emotional aspects of remembering personal events (but see 10). Here, we present a protocol that allows investigation of the neural correlates of recollecting emotional AMs using functional magnetic resonance imaging (fMRI). Cues for these memories are collected prior to scanning by means of an autobiographical memory questionnaire (AMQ), therefore allowing for proper selection of emotional AMs based on their phenomenological properties (i.e., intensity, vividness, personal significance). This protocol can be used in healthy and clinical populations alike.

We present a protocol that allows investigation of the neural correlates of recollecting emotional autobiographical memories, using functional magnetic resonance imaging. This protocol can be used with both healthy and clinical participants.

情感自传回忆的神经关联的脑成像研究

Recollection of emotional autobiographical memories (AMs) is important to healthy cognitive and affective functioning 1 - remembering positive AMs is ...

Brain Imaging Investigation of the Neural Correlates of Emotion Regulation

The ability to control/regulate emotions is an important coping mechanism in the face of emotionally stressful situations. Although significant progress has been made in understanding conscious/deliberate emotion regulation (ER), less is known about non-conscious/automatic ER and the associated neural correlates. This is in part due to the problems inherent in the unitary concepts of automatic and conscious processing1. Here, we present a protocol that allows investigation of the neural correlates of both deliberate and automatic ER using functional magnetic resonance imaging (fMRI). This protocol allows new avenues of inquiry into various aspects of ER. For instance, the experimental design allows manipulation of the goal to regulate emotion (conscious vs. non-conscious), as well as the intensity of the emotional challenge (high vs. low). Moreover, it allows investigation of both immediate (emotion perception) and long-term effects (emotional memory) of ER strategies on emotion processing. Therefore, this protocol may contribute to better understanding of the neural mechanisms of emotion regulation in healthy behaviour, and to gaining insight into possible causes of deficits in depression and anxiety disorders in which emotion dysregulation is often among the core debilitating features.

We present a protocol that allows investigation of the neural correlates of deliberate and automatic emotion regulation, using functional magnetic resonance imaging. This protocol can be used in healthy participants, both young and older, as well as in clinical patients.

情绪调节的神经关联的脑成像研究

The ability to control/regulate emotions is an important coping mechanism in the face of emotionally stressful situations. Although significant progress ...

Brain Imaging Investigation of the Memory-Enhancing Effect of Emotion

Emotional events tend to be better remembered than non-emotional events1,2. One goal of cognitive and affective neuroscientists is 
to understand the neural mechanisms underlying this enhancing effect of emotion on memory. A method that has proven particularly influential in the 
investigation of the memory-enhancing effect of emotion is the so-called subsequent memory paradigm (SMP). This method was originally used to investigate the 
neural correlates of non-emotional memories3, and more recently we and others also applied it successfully to studies of emotional memory (reviewed in4, 5-7). 
Here, we describe a protocol that allows investigation of the neural correlates of the memory-enhancing effect of emotion using the SMP in conjunction with 
event-related functional magnetic resonance imaging (fMRI). An important feature of the SMP is that it allows separation of brain activity specifically 
associated with memory from more general activity associated with perception. Moreover, in the context of investigating the impact of emotional stimuli, 
SMP allows identification of brain regions whose activity is susceptible to emotional modulation of both general/perceptual and memory-specific processing. 
This protocol can be used in healthy subjects8-15, as well as in clinical patients where there are alterations in the neural correlates of emotion perception 
and biases in remembering emotional events, such as those suffering from depression and post-traumatic stress disorder (PTSD)16, 17.

We present a protocol that uses functional magnetic resonance imaging to investigate the neural correlates of the memory-enhancing effect of emotion. This protocol allows identification of brain activity specifically linked to memory-related processing, contrary to more general perceptual processing, and can be used with healthy and clinical populations.

脑成像的情感记忆的促进作用调查

Emotional events tend to be better remembered than non-emotional events1,2. One goal of cognitive and affective neuroscientists is 
to understand the ...

Enabling High Grayscale Resolution Displays and Accurate Response Time Measurements on Conventional Computers

Display systems based on conventional computer graphics cards are capable of generating images with 8-bit gray level resolution. However, most experiments in vision research require displays with more than 12 bits of luminance resolution. Several solutions are available. Bit++ 1 and DataPixx 2 use the Digital Visual Interface (DVI) output from graphics cards and high resolution (14 or 16-bit) digital-to-analog converters to drive analog display devices. The VideoSwitcher 3 described here combines analog video signals from the red and blue channels of graphics cards with different weights using a passive resister network 4 and an active circuit to deliver identical video signals to the three channels of color monitors. The method provides an inexpensive way to enable high-resolution monochromatic displays using conventional graphics cards and analog monitors. It can also provide trigger signals that can be used to mark stimulus onsets, making it easy to synchronize visual displays with physiological recordings or response time measurements.
Although computer keyboards and mice are frequently used in measuring response times (RT), the accuracy of these measurements is quite low. The RTbox is a specialized hardware and software solution for accurate RT measurements. Connected to the host computer through a USB connection, the driver of the RTbox is compatible with all conventional operating systems. It uses a microprocessor and high-resolution clock to record the identities and timing of button events, which are buffered until the host computer retrieves them. The recorded button events are not affected by potential timing uncertainties or biases associated with data transmission and processing in the host computer. The asynchronous storage greatly simplifies the design of user programs. Several methods are available to synchronize the clocks of the RTbox and the host computer. The RTbox can also receive external triggers and be used to measure RT with respect to external events. 
Both VideoSwitcher and RTbox are available for users to purchase. The relevant information and many demonstration programs can be found at <a href="http://lobes.usc.edu/">http://lobes.usc.edu/</a>.

Conventional computer hardware can not generate visual stimuli with sufficiently high grayscale resolution and measure response times with sufficient accuracy. We describe how to use the VideoSwitcher to produce high-resolution monochromatic displays, and the RTbox to measure response times with high accuracy on conventional computer hardware.

启用高灰度分辨率的显示器和传统计算机准确的响应时间测量

Display systems based on conventional computer graphics cards are capable of generating images with 8-bit gray level resolution. However, most experiments ...

Co-analysis of Brain Structure and Function using fMRI and Diffusion-weighted Imaging

The study of complex computational systems is facilitated by network maps, such as circuit diagrams. Such mapping is particularly informative when studying the brain, as the functional role that a brain area fulfills may be largely defined by its connections to other brain areas. In this report, we describe a novel, non-invasive approach for relating brain structure and function using magnetic resonance imaging (MRI). This approach, a combination of structural imaging of long-range fiber connections and functional imaging data, is illustrated in two distinct cognitive domains, visual attention and face perception. Structural imaging is performed with diffusion-weighted imaging (DWI) and fiber tractography, which track the diffusion of water molecules along white-matter fiber tracts in the brain (Figure 1). By visualizing these fiber tracts, we are able to investigate the long-range connective architecture of the brain. The results compare favorably with one of the most widely-used techniques in DWI, diffusion tensor imaging (DTI). DTI is unable to resolve complex configurations of fiber tracts, limiting its utility for constructing detailed, anatomically-informed models of brain function. In contrast, our analyses reproduce known neuroanatomy with precision and accuracy. This advantage is partly due to data acquisition procedures: while many DTI protocols measure diffusion in a small number of directions (e.g., 6 or 12), we employ a diffusion spectrum imaging (DSI)1, 2 protocol which assesses diffusion in 257 directions and at a range of magnetic gradient strengths. Moreover, DSI data allow us to use more sophisticated methods for reconstructing acquired data. In two experiments (visual attention and face perception), tractography reveals that co-active areas of the human brain are anatomically connected, supporting extant hypotheses that they form functional networks. DWI allows us to create a "circuit diagram" and reproduce it on an individual-subject basis, for the purpose of monitoring task-relevant brain activity in networks of interest.

We describe a novel approach for simultaneous analysis of brain function and structure using magnetic resonance imaging (MRI). We assess brain structure with high-resolution diffusion-weighted imaging and white-matter fiber tractography. Unlike standard structural MRI, these techniques allow us to directly relate anatomical connectivity to functional properties of brain networks.

使用功能磁共振成像和弥散加权成像脑结构与功能分析

The study of complex computational systems is facilitated by network maps, such as circuit diagrams. Such mapping is particularly informative when ...

In Vivo Two-photon Imaging Of Experience-dependent Molecular Changes In Cortical Neurons

The brain's ability to change in response to experience is essential for healthy brain function, and abnormalities in this process contribute to a variety of brain disorders1,2. To better understand the mechanisms by which brain circuits react to an animal's experience requires the ability to monitor the experience-dependent molecular changes in a given set of neurons, over a prolonged period of time, in the live animal. While experience and associated neural activity is known to trigger gene expression changes in neurons1,2, most of the methods to detect such changes do not allow repeated observation of the same neurons over multiple days or do not have sufficient resolution to observe individual neurons3,4. Here, we describe a method that combines in vivo two-photon microscopy with a genetically encoded fluorescent reporter to track experience-dependent gene expression changes in individual cortical neurons over the course of day-to-day experience. 
One of the well-established experience-dependent genes is Activity-regulated cytoskeletal associated protein (Arc)5,6. The transcription of Arc is rapidly and highly induced by intensified neuronal activity3, and its protein product regulates the endocytosis of glutamate receptors and long-term synaptic plasticity7. The expression of Arc has been widely used as a molecular marker to map neuronal circuits involved in specific behaviors3. In most of those studies, Arc expression was detected by in situ hybridization or immunohistochemistry in fixed brain sections. Although those methods revealed that the expression of Arc was localized to a subset of excitatory neurons after behavioral experience, how the cellular patterns of Arc expression might change with multiple episodes of repeated or distinctive experiences over days was not investigated. 
In vivo two-photon microscopy offers a powerful way to examine experience-dependent cellular changes in the living brain8,9. To enable the examination of Arc expression in live neurons by two-photon microscopy, we previously generated a knock-in mouse line in which a GFP reporter is placed under the control of the endogenous Arc promoter10. This protocol describes the surgical preparations and imaging procedures for tracking experience-dependent Arc-GFP expression patterns in neuronal ensembles in the live animal. In this method, chronic cranial windows were first implanted in Arc-GFP mice over the cortical regions of interest. Those animals were then repeatedly imaged by two-photon microscopy after desired behavioral paradigms over the course of several days. This method may be generally applicable to animals carrying other fluorescent reporters of experience-dependent molecular changes4.

In Vivo Two-photon Imaging Of Experience-dependent Molecular Changes In Cortical Neurons

Experience-dependent molecular changes in neurons are essential for the brain's ability to adapt in response to behavioral challenges. An in vivo two-photon imaging method is described here that allows the tracking of such molecular changes in individual cortical neurons through genetically encoded reporters.

在体内双光子成像的经验依赖的分子在大脑皮质神经元的变化

The brain's ability to change in response to experience is essential for healthy brain function, and abnormalities in this process contribute to a variety ...

A Dual Tracer PET-MRI Protocol for the Quantitative Measure of Regional Brain Energy Substrates Uptake in the Rat

We present a method for comparing the uptake of the brain&#39;s two key energy substrates: glucose and ketones (acetoacetate [AcAc] in this case) in the rat. The developed method is a small-animal positron emission tomography (PET) protocol, in which&#160;11C-AcAc and 18F-fluorodeoxyglucose (18F-FDG) are injected sequentially in each animal. This dual tracer PET acquisition is possible because of the short half-life of 11C (20.4 min). The rats also undergo a magnetic resonance imaging (MRI) acquisition seven days before the PET protocol. Prior to image analysis, PET and MRI images are coregistered to allow the measurement of regional cerebral uptake (cortex, hippocampus, striatum, and cerebellum). A quantitative measure of 11C-AcAc and 18F-FDG brain uptake (cerebral metabolic rate; &#956;mol/100 g/min) is determined by kinetic modeling using the image-derived input function (IDIF) method. Our new dual tracer PET protocol is robust and flexible; the two tracers used can be replaced by different radiotracers to evaluate other processes in the brain. Moreover, our protocol is applicable to the study of brain fuel supply in multiple conditions such as normal aging and neurodegenerative pathologies such as Alzheimer&#39;s and Parkinson&#39;s diseases.

Small-animal positron emission tomography enables the assessment of the brain&#39;s two main energy substrates:&#160;glucose and ketones. In the present method, 11C-acetoacetate and 18F-fluorodeoxyglucose are injected sequentially in each animal, and their uptake is measured quantitatively in specific brain regions determined from the magnetic resonance images.

We present a method for comparing the uptake of the brain&#39;s two key energy substrates: glucose and ketones (acetoacetate [AcAc] in this case) in the ...

Stereotaxic Infusion of Oligomeric Amyloid-beta into the Mouse Hippocampus

Alzheimer&#8217;s disease is a neurodegenerative disease affecting the aging population. A key neuropathological feature of the disease is the over-production of amyloid-beta and the deposition of amyloid-beta plaques in brain regions of the afflicted individuals. Throughout the years scientists have generated numerous Alzheimer&#8217;s disease mouse models that attempt to replicate the amyloid-beta pathology. Unfortunately, the mouse models only selectively mimic the disease features. Neuronal death, a prominent effect in the brains of Alzheimer&#8217;s disease patients, is noticeably lacking in these mice. Hence, we and others have employed a method of directly infusing soluble oligomeric species of amyloid-beta - forms of amyloid-beta that have been proven to be most toxic to neurons - stereotaxically into the brain. In this report we utilize male C57BL/6J mice to document this surgical technique of increasing amyloid-beta levels in a select brain region. The infusion target is the dentate gyrus of the hippocampus because this brain structure, along with the basal forebrain that is connected by the cholinergic circuit, represents one of the areas of degeneration in the disease. The results of elevating amyloid-beta in the dentate gyrus via stereotaxic infusion reveal increases in neuron loss in the dentate gyrus within 1 week, while there is a concomitant increase in cell death and cholinergic neuron loss in the vertical limb of the diagonal band of Broca of the basal forebrain. These effects are observed up to 2 weeks. Our data suggests that the current amyloid-beta infusion model provides an alternative mouse model to address region specific neuron death in a short-term basis. The advantage of this model is that amyloid-beta can be elevated in a spatial and temporal manner.

Here, we present a protocol for direct stereotaxic brain infusion of amyloid-beta. This methodology provides an alternative in vivo mouse model to address the short-term effects of amyloid-beta on brain neurons.