이 작품은 캐나다 자연 과학 및 공학 연구 위원회 (NSERC)에서 BDC에 디스커버리 그랜트에 의해 지원됩니다; RGPIN 311680) 및 건강 연구의 캐나다 연구소에서 BDC에 운영 보조금 (CIHR; MOP-93796). RAK는 온타리오 대학원 장학금의 지원을 받았으며, ALC는 NSERC CREATE 보조금의 지원을 받았습니다. 이 원고에 설명된 실험 장치는 캐나다 혁신 재단에 의해 지원되었다. 추가 지원은 캐나다 제1 연구 우수 기금 (BrainsCAN)에서 왔다.

<ol>
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L., Brown, P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Evidence+for+subcortical+involvement+in+the+visual+control+of+human+reaching.">Evidence for subcortical involvement in the visual control of human reaching.</a> Brain A Journal of Neurology. 124, 1832-1840 (2001).</li><li>Pruszynski, A. J., 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=Stimulus-locked+responses+on+human+arm+muscles+reveal+a+rapid+neural+pathway+linking+visual+input+to+arm+motor+output.">Stimulus-locked responses on human arm muscles reveal a rapid neural pathway linking visual input to arm motor output.</a> European Journal of Neuroscience. 32 (6), 1049-1057 (2010).</li><li>Corneil, B. D., Olivier, E., Munoz, D. P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Visual+responses+on+neck+muscles+reveal+selective+gating+that+prevents+express+saccades.">Visual responses on neck muscles reveal selective gating that prevents express saccades.</a> Neuron. 42 (5), 831-841 (2004).</li><li>Wood, D. K., Gu, C., Corneil, B. D., Gribble, P. L., Goodale, M. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Transient+visual+responses+reset+the+phase+of+low-frequency+oscillations+in+the+skeletomotor+periphery.">Transient visual responses reset the phase of low-frequency oscillations in the skeletomotor periphery.</a> European Journal of Neuroscience. 42 (3), 1919-1932 (2015).</li><li>Gu, C., Wood, D. K., Gribble, P. L., Corneil, B. 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+Trial-by-Trial+Window+into+Sensorimotor+Transformations+in+the+Human+Motor+Periphery.">A Trial-by-Trial Window into Sensorimotor Transformations in the Human Motor Periphery.</a> Journal of Neuroscience. 36 (31), 8273-8282 (2016).</li><li>Kozak, R. A., Kreyenmeier, P., Gu, C., Johnston, K., Corneil, B. D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Stimulus-locked+responses+on+human+upper+limb+muscles+and+corrective+reaches+are+preferentially+evoked+by+low+spatial+frequencies.">Stimulus-locked responses on human upper limb muscles and corrective reaches are preferentially evoked by low spatial frequencies.</a> eNeuro. 6 (5), (2019).</li><li>Kowler, E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Cognitive+expectations,+not+habits,+control+anticipatory+smooth+oculomotor+pursuit.">Cognitive expectations, not habits, control anticipatory smooth oculomotor pursuit.</a> Vision Research. 29 (9), 1049-1057 (1989).</li><li>Goonetilleke, S. C., 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=Cross-species+comparison+of+anticipatory+and+stimulus-driven+neck+muscle+activity+well+before+saccadic+gaze+shifts+in+humans+and+nonhuman+primates.">Cross-species comparison of anticipatory and stimulus-driven neck muscle activity well before saccadic gaze shifts in humans and nonhuman primates.</a> Journal of Neurophysiology. 114 (2), 902-913 (2015).</li><li>Franklin, D. W., Reichenbach, A., Franklin, S., Diedrichsen, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Temporal+evolution+of+spatial+computations+for+visuomotor+control.">Temporal evolution of spatial computations for visuomotor control.</a> Journal of Neuroscience. 36 (8), 2329-2341 (2016).</li><li>Krekelberg, B., Vatakis, A., Kourtzi, Z. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Implied+motion+from+form+in+the+human+visual+cortex.">Implied motion from form in the human visual cortex.</a> Journal of Neurophysiology. 94 (6), 4373-4386 (2005).</li><li>Gribble, P. L., Everling, S., Ford, K., Mattar, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Hand-eye+coordination+for+rapid+pointing+movements:+Arm+movement+direction+and+distance+are+specified+prior+to+saccade+onset.">Hand-eye coordination for rapid pointing movements: Arm movement direction and distance are specified prior to saccade onset.</a> Experimental Brain Research. 145 (3), 372-382 (2002).</li><li>Par&#233;, M., Munoz, D. P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Saccadic+reaction+time+in+the+monkey:+advanced+preparation+of+oculomotor+programs+is+primarily+responsible+for+express+saccade+occurrence.">Saccadic reaction time in the monkey: advanced preparation of oculomotor programs is primarily responsible for express saccade occurrence.</a> Journal of Neurophysiology. 76 (6), 3666-3681 (1996).</li></ol>

저자는 공개 할 것이 없습니다.

인간은 필요한 경우 최소한의 방신 및 효능 전도 지연에 접근하는 신속하고 시각적으로 유도된 행동을 생성할 수 있는 놀라운 능력을 가지고 있습니다. 앞서 상측에 자극-잠긴 응답(SR)을 빠른 바이저모터 응답6,9,10에대한 새로운 척도로 기술하였다. 시각적 자극에 의해 영향을 받는 상반신 근육 모집의 첫 번째 측면에 대 한 재...

핸드폰에 메시지를 받으면 시각적으로 안내된 연락을 수행하여 휴대폰을 수령하고 메시지를 읽으라는 메시지가 표시됩니다. 휴대 전화의 모양과 크기와 같은 시각적 기능은 모터 명령으로 변환되어 목표에 성공적으로 도달 할 수 있습니다. 이러한 visuomotor 변환 은 높은 수준의 제어를 허용하는 실험실 조건에서 연구 될 수있다. 그러나 응답 시간이 중요한 시나리오(예: 넘어질 경우 전화 잡기)가 있습니다. 빠른 visuomotor 행동의 실험실 연구는 종종 대상 위치의 일부 변화에 따라 비행 중 에서 진행 중인 움직임이 수정되는 변위 대상 패러다임에 의존합니다 (예 : 참조1,2). 이러한 온라인 보정은 & 150 ms3에서발생할 수 있지만, 팔의 로우 패스 필터링 특성으로 인해 운동학을 사용하여 빠른 visuomotor 출력의 정확한 타이밍을 확인하기가 어렵고 빠른 visuomotor 출력은 비행 중 이미 움직임을 대체하기 때문에. 이러한 합병증은 빠른 visuomotor 반응의 근본적인 기판에 대한 불확실성으로 이끌어 내습니다 (검토를 위한 참조4 참조). 일부 연구에 따르면 전두엽 피질 영역이 아닌 우수한 콜리큘러스와 같은 하위 구조가 온라인 보정을 시작할 수 있다고5.
근본적인 신경 기판에 관하여 이 불확실성은, 적어도 부분적으로, 빠른 visuomotor 시스템의 출력을 위한 믿을 수 있는 biomarker의 부족에 기인할 수 있습니다. 최근에는 정전기촬영(EMG)을 통해 정적 자세에서 생성되고 기록될 수 있는 빠른 바이저모터 반응의 측정을 설명했습니다. 자극-잠긴 응답(SR)은 자극 개시 후 지속적으로 ~100ms를 진화시키는 자발적 운동6,7,진화를 앞둔 EMG 활동의 시간 잠긴 버스트이다. 이름에서 알 수 있듯이, SLA는 자극 개시에 의해 연상되며, 최종 움직임이8을 보류하거나 반대 방향으로 이동하더라도지속됩니다 9. 또한 동적 패러다임에서 표적 변위로 인해 유발되는 SR은 짧은 대기 시간 온라인보정(10)과연관된다. 따라서, SR은 짧은 대기 시간 RT에 관여하는 빠른 바이저모터 시스템의 출력을 체계적으로 연구하기 위한 객관적인 측정을 제공하며, 이는 정적 자세로부터 생성되고 빠른 visuomotor 반응의 초기 단계와 관련이 없는 다른 EMG 신호로부터 구문 분석될 수 있기 때문에.
현재 연구의 목표는 SLA를 강력하게 유도하는 시각적으로 유도된 도달 패러다임을 제시하는 것입니다. SLR을 조사하는 이전 연구는 더 침략적인 근육 내 기록을 사용하는 경우에도 참가자에 걸쳐 100 % 미만의검출률을보고6,8,9. 낮은 검출 률과 침습적 기록에 대한 의존도는 질병 또는 수명 전반에 걸친 빠른 visuomotor 시스템에 대한 향후 조사에서 SLR 조치의 유용성을 제한합니다. 일부 과목은 단순히 SLR을 표현하지 않을 수 있지만, 이전에 사용 된 자극과 행동 패러다임은 SLR을 연상이상하지 않았을 수 있습니다. SR의 과거 보고서는 일반적으로 참가자가 갑자기 나타나는 대상6,9를향해 시각적으로 유도 된 도달을 생성하는 패러다임을 사용했다. 그러나 빠른 바이저모터 시스템은 낙하 또는 비행 물체와 빠르게 상호 작용해야 하는 시나리오에서 가장 필요한 시스템이며, 정적 자극보다는 움직이는 것이 SR을 더 잘 불러일으킬 수 있는지 궁금해합니다. 따라서, 우리는 눈 의 움직임을 연구하는 데 사용되는움직이는 대상 패러다임을 적응하고, SLR9을검사하는 데 사용되는 프로 / 안티 시각적으로 유도 도달 작업과 결합했다. 이전에 사용 된 패러다임의 결과와 비교했을 때6,8,9,신흥 대상 패러다임의 SLA가 더 빨리 진화하고, 더 높은 크기를 달성했으며, 참가자 샘플 전반에 걸쳐 더 널리 퍼졌다는 것을 발견했습니다. 전반적으로, 신흥 표적 패러다임은 객관적인 EMG 측정이 표면 기록, 임상 인구 내 및 수명 전반에 걸쳐 전능한 연구 결과로 안정적으로 이루어질 수 있는 정도로 빠른 visuomotor 반응의 표현을 촉진합니다. 또한, 새로운 표적 패러다임을 여러 가지 방법으로 수정하여 빠른 visuomotor 응답을 촉진하거나 수정하는 감각, 인지 및 모터 요인에 대한 보다 철저한 조사를 촉진할 수 있습니다.

<table>
	<tbody>
		<tr>
			<td>Bagnoli-8 Desktop Surface EMG System</td>
			<td>Delsys Inc.</td>
			<td></td>
			<td>Another reaching apparatus may be used</td>
		</tr>
		<tr>
			<td>Kinarm End-Point Robot</td>
			<td>Kinarm, Kingston, Ontario, Canada</td>
			<td></td>
			<td>Another reaching apparatus may be used</td>
		</tr>
		<tr>
			<td>MATLAB (version R2016a) Stateflow and Simulink applications</td>
			<td>The MathWorks, Inc., Natick, Massachusetts, United States</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>PROPixx projector</td>
			<td>VPIXX Saint-Bruno, QC, Canada</td>
			<td></td>
			<td>This is a custom built addon for the Kinarm. Other displays may be used.</td>
		</tr>
		<tr>
			<td></td>
			<td></td>
			<td></td>
			<td>Resolution: 1920 x 1080. Standard viewing monitors may also be used.</td>
		</tr>
	</tbody>
</table>

an emerging target paradigm to evoke fast visuomotor responses on human upper limb muscles

볼 수 있는 물체를 향해 도달하려면 시각적 정보를 모터 명령으로 변환해야 합니다. 물체의 색상, 모양 및 크기와 같은 시각적 정보는 수많은 뇌 영역 내에서 처리되고 통합된 다음 궁극적으로 모터 주변으로 전달됩니다. 어떤 경우에는 가능한 한 빨리 반응이 필요합니다. 이러한 빠른 visuomotor 변환, 그리고 그들의 근본적인 신경 기질, 그들은 신뢰할 수 있는 바이오 마커 부족으로 인간에서 제대로 이해. 자극-잠긴 응답(SR)은 시각 자극 프리젠테이션에 의해 영향을 받은 근육 모집의 첫 번째 물결을 나타내는 짧은 대기 시간(&100 ms) 전동(EMG) 활동의 파열입니다. SR은 급속한 바이저모터 변환의 정량화 가능한 출력을 제공하지만, SR은 과거 연구의 모든 과목에서 일관되게 관찰되지 않았습니다. 여기서 우리는 지속적으로 강력한 SR을 연상시키는 장애물 아래 움직이는 대상의 갑작스런 출현을 특징으로하는 새로운 행동 패러다임을 설명합니다. 인간 참가자는 표면 전극이 가슴 주요 근육에서 EMG 활동을 기록하는 동안 로봇 매니풀란덤을 사용하여 신흥 대상을 향해 또는 멀리 유도 생성. 정적 자극을 사용하여 SR을 조사한 이전 연구와 비교하여, 이 새로운 표적 패러다임으로 불러온 SR은 더 크고, 더 일찍 진화했으며, 모든 참가자에게 존재했습니다. 도달 반응 시간(RTs)도 신흥 표적 패러다임에서 신속히 처리되었다. 이 패러다임은 다양한 감각, 인지 및 모터 조작이 빠른 visuomotor 반응에 미치는 영향에 대한 체계적인 연구를 허용할 수 있는 수많은 수정 기회를 제공합니다. 전반적으로, 우리의 결과는 새로운 표적 패러다임이 빠른 visuomotor 시스템 내에서 일관되고 강력하게 활동을 불러 올 수 있다는 것을 보여줍니다.

자극 잠긴 응답 (SR) 근육 활동 시간의 짧은 버스트 운동 발병과 관련 된 근육 모집의 큰 발리 전에 잘 진화 하는 자극 개시에 잠겨. SLR의 시간 잠긴 특성은 반응 시간(RT)(그림1a,회색 상자로 강조 표시)을 위해 정렬된 모든 시험을 볼 때 ~100 ms에서 보이는 근육 활동의 '밴딩'을 생성했습니다. 도 1a에도시된 바와 같이, SR은 표적 위치에 의존했으며, 오른쪽 ?...

Watch this Scientific Journal Video about An Emerging Target Paradigm to Evoke Fast Visuomotor Responses on Human Upper Limb Muscles at JoVE.com

An Emerging Target Paradigm to Evoke Fast Visuomotor Responses on Human Upper Limb Muscles

여기에 제시 시각적으로 유도 도달 하는 동안 인간의 상부 사지 근육에 강력한 빠른 visuomotor 응답을 유도 하는 행동 패러다임.

인간의 상반신 근육에 빠른 Visuomotor 응답을 불러 일으키는 신흥 대상 패러다임

To reach towards a seen object, visual information has to be transformed into motor commands. Visual information such as the object&#8217;s color, shape, ...

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Neuroscience

4.2K 조회수.  Western University. 여기에 제시 시각적으로 유도 도달 하는 동안 인간의 상부 사지 근육에 강력한 빠른 visuomotor 응답을 유도 하는 행동 패러다임.

비디오: An Emerging Target Paradigm to Evoke Fast Visuomotor Responses on Human Upper Limb Muscles

Recording Behavioral Responses to Reflection in Crayfish

Social behavior depends on sensory input from the visual, mechanical and olfactory systems. One important issue concerns the relative roles of each sensory modality in guiding behavior. The role of visual inputs has been examined by isolating visual stimuli from mechanical and chemosensory stimuli. In some studies (Bruski &amp; Dunham, 1987: Delgado-Morales et al., 2004) visual inputs have been removed with blindfolds or low light intensity, and effects of remaining sensory modalities have been elucidated. An alternative approach is to study the effects of visual inputs in the absence of any appropriate mechanical and chemosensory cues. This approach aims to identify the exclusive role of visual inputs. 
We have used two methods to provide visual stimuli to crayfish without providing chemical and mechanical cues. In one method, crayfish are videotaped in an aquarium where half of the walls are covered in mirrors to provide a reflective environment, and the other half are covered in a non-reflective (matte finish) plastic. This gives the crayfish a choice between reflective and non-reflective environments. The reflective environment provides visual cues in the form of reflected images of the crayfish as it moves throughout half of the tank; these visual cues are missing from the non-reflective half of the tank. An alternative method is to videotape the behavior of crayfish in an aquarium separated by a smaller chamber at each end, with a crayfish in one small chamber providing visual cues and an inert object in the opposite small chamber providing visual input from a non-moving, non-crayfish source. 
Our published results indicate that responses of crayfish to the reflective environment depend on socialization and dominance rank. Socialized crayfish spent more time in the reflective environment and exhibited certain behaviors more frequently there than in the non-reflective environment; isolated crayfish showed no such differences. Crayfish that were housed in same-sex pairs developed a social rank of either dominant or subordinate. Responses to reflection differed between dominant and subordinate crayfish (May &amp; Mercier, 2006; May &amp; Mercier, 2007). Dominant crayfish spent more time on the reflective side, entered reflective corners more frequently and spent more time in reflective corners compared to the non-reflective side. Subordinate crayfish walked in reverse more often on the reflective side than on the non-reflective side. Preliminary data suggest similar effects from visual cues provided by a crayfish in a small adjoining chamber (May et al., 2008).

We have developed two methods for studying effects of visual cues on behavior in the absence of tactile and chemical cues. One method involves videotaping responses of crayfish to reflective walls in an aquarium; the other examines effects of visual inputs provided by a live crayfish behind a transparent partition.

크레이 피쉬에 리플렉션하는 행동 응답 녹음

Social behavior depends on sensory input from the visual, mechanical and olfactory systems.  One important issue concerns the relative roles of each ...

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신경과학

Vibrodissociation of Neurons from Rodent Brain Slices to Study Synaptic Transmission and Image Presynaptic Terminals

Mechanical dissociation of neurons from the central nervous system has the advantage that presynaptic boutons remain attached to the isolated neuron of interest. This allows for examination of synaptic transmission under conditions where the extracellular and postsynaptic intracellular environments can be well controlled. A vibration-based technique without the use of proteases, known as vibrodissociation, is the most popular technique for mechanical isolation. A micropipette, with the tip fire-polished to the shape of a small ball, is placed into a brain slice made from a P1-P21 rodent. The micropipette is vibrated parallel to the slice surface and lowered through the slice thickness resulting in the liberation of isolated neurons. The isolated neurons are ready for study within a few minutes of vibrodissociation. This technique has advantages over the use of primary neuronal cultures, brain slices and enzymatically isolated neurons including: rapid production of viable, relatively mature neurons suitable for electrophysiological and imaging studies; superior control of the extracellular environment free from the influence of neighboring cells; suitability for well-controlled pharmacological experiments using rapid drug application and total cell superfusion; and improved space-clamp in whole-cell recordings relative to neurons in slice or cell culture preparations. This preparation can be used to examine synaptic physiology, pharmacology, modulation and plasticity. Real-time imaging of both pre- and postsynaptic elements in the living cells and boutons is also possible using vibrodissociated neurons. Characterization of the molecular constituents of pre- and postsynaptic elements can also be achieved with immunological and imaging-based approaches.

This report demonstrates a technique for mechanical isolation of individual viable neurons retaining attached presynaptic boutons. Vibrodissociated neurons have the advantages of rapid production, excellent pharmacological control and improved space-clamp without influence from neighboring cells. This method can be used for imaging of synaptic elements and patch-clamp recording.

쥐 뇌 조각에서 뉴런의 Vibrodissociation는 시냅틱 전송 및 이미지 Presynaptic 터미널 공부

Mechanical dissociation of neurons from the central nervous system has the advantage that presynaptic boutons remain attached to the isolated neuron of ...

Correlating Behavioral Responses to fMRI Signals from Human Prefrontal Cortex: Examining Cognitive Processes Using Task Analysis

The aim of this methods paper is to describe how to implement a neuroimaging technique to examine complementary brain processes engaged by two similar tasks. Participants' behavior during task performance in an fMRI scanner can then be correlated to the brain activity using the blood-oxygen-level-dependent signal. We measure behavior to be able to sort correct trials, where the subject performed the task correctly and then be able to examine the brain signals related to correct performance. Conversely, if subjects do not perform the task correctly, and these trials are included in the same analysis with the correct trials we would introduce trials that were not only for correct performance. Thus, in many cases these errors can be used themselves to then correlate brain activity to them. We describe two complementary tasks that are used in our lab to examine the brain during suppression of an automatic responses: the stroop1 and anti-saccade tasks. The emotional stroop paradigm instructs participants to either report the superimposed emotional 'word' across the affective faces or the facial 'expressions' of the face stimuli1,2. When the word and the facial expression refer to different emotions, a conflict between what must be said and what is automatically read occurs. The participant has to resolve the conflict between two simultaneously competing processes of word reading and facial expression. Our urge to read out a word leads to strong 'stimulus-response (SR)' associations; hence inhibiting these strong SR's is difficult and participants are prone to making errors. Overcoming this conflict and directing attention away from the face or the word requires the subject to inhibit bottom up processes which typically directs attention to the more salient stimulus. Similarly, in the anti-saccade task3,4,5,6, where an instruction cue is used to direct only attention to a peripheral stimulus location but then the eye movement is made to the mirror opposite position. Yet again we measure behavior by recording the eye movements of participants which allows for the sorting of the behavioral responses into correct and error trials7 which then can be correlated to brain activity. Neuroimaging now allows researchers to measure different behaviors of correct and error trials that are indicative of different cognitive processes and pinpoint the different neural networks involved.

The goal of our research is to correlate behavior to brain activity. Accurate behavioral measures and imaging techniques allow us to elucidate brain-behavior relationships.

인간의 전두엽 피질에서 fMRI 신호에 행동 응답을 연관 : 작업 분석을 사용하여인지 과정을 검토

The aim of this methods paper is to describe how to implement a neuroimaging technique to examine complementary brain processes engaged by two similar ...

An Injury Paradigm to Investigate Central Nervous System Repair in Drosophila

An experimental method has been developed to investigate the cellular responses to central nervous system (CNS) injury using the fruit-fly Drosophila. Understanding repair and regeneration in animals is a key question in biology. The damaged human CNS does not regenerate, and understanding how to promote the regeneration is one of main goals of medical neuroscience. The powerful genetic toolkit of Drosophila can be used to tackle the problem of CNS regeneration.
A lesion to the CNS ventral nerve cord (VNC, equivalent to the vertebrate spinal cord) is applied manually with a tungsten needle. The VNC can subsequently be filmed in time-lapse using laser scanning confocal microscopy for up to 24 hr to follow the development of the lesion over time. Alternatively, it can be cultured, then fixed and stained using immunofluorescence to visualize neuron and glial cells with confocal microscopy. Using appropriate markers, changes in cell morphology and cell state as a result of injury can be visualized. With ImageJ and purposely developed plug-ins, quantitative and statistical analyses can be carried out to measure changes in wound size over time and the effects of injury in cell proliferation and cell death. These methods allow the analysis of large sample sizes. They can be combined with the powerful genetics of Drosophila to investigate the molecular mechanisms underlying CNS regeneration and repair.

An Injury Paradigm to Investigate Central Nervous System Repair in Drosophila

An injury paradigm using the Drosophila larval ventral nerve cord to investigate central nervous system regeneration and repair is described. Stabbing followed by laser scanning confocal microscopy in time-lapse and fixed specimens, combined with quantitative analysis with purposefully developed software and genetics, are used to investigate the molecular mechanisms of CNS regeneration and repair.

에 중추 신경 시스템 복구를 조사하기 위해 상해 패러다임<em&gt; Drosophila</em

An experimental method has been developed to investigate the cellular responses to central nervous system (CNS) injury using the fruit-fly Drosophila. ...

Electrophysiological Method for Recording Intracellular Voltage Responses of Drosophila Photoreceptors and Interneurons to Light Stimuli In Vivo

Voltage responses of insect photoreceptors and visual interneurons can be accurately recorded with conventional sharp microelectrodes. The method described here enables the investigator to measure long-lasting (from minutes to hours) high-quality intracellular responses from single Drosophila R1-R6 photoreceptors and Large Monopolar Cells (LMCs) to light stimuli. Because the recording system has low noise, it can be used to study variability among individual cells in the fly eye, and how their outputs reflect the physical properties of the visual environment. We outline all key steps in performing this technique. The basic steps in constructing an appropriate electrophysiology set-up for recording, such as design and selection of the experimental equipment are described. We also explain how to prepare for recording by making appropriate (sharp) recording and (blunt) reference electrodes. Details are given on how to fix an intact fly in a bespoke fly-holder, prepare a small window in its eye and insert a recording electrode through this hole with minimal damage. We explain how to localize the center of a cell's receptive field, dark- or light-adapt the studied cell, and to record its voltage responses to dynamic light stimuli. Finally, we describe the criteria for stable normal recordings, show characteristic high-quality voltage responses of individual cells to different light stimuli, and briefly define how to quantify their signaling performance. Many aspects of the method are technically challenging and require practice and patience to master. But once learned and optimized for the investigator's experimental objectives, it grants outstanding in vivo neurophysiological data.

Electrophysiological Method for Recording Intracellular Voltage Responses of Drosophila Photoreceptors and Interneurons to Light Stimuli In Vivo

Sharp microelectrodes enable accurate electrophysiological characterization of photoreceptor and visual interneuron output in living Drosophila. Here we show how to use this method to record high-quality voltage responses of individual cells to controlled light stimulation. This method is ideal for studying neural information processing in insect compound eyes.

의 기록 세포 내 전압 응답에 대한 전기 생리 방법<em&gt; 초파리</em&gt; 빛 자극에 광수와의 interneurons<em&gt; 생체</em

Voltage responses of insect photoreceptors and visual interneurons can be accurately recorded with conventional sharp microelectrodes. The method ...

A Computerized Test Battery to Study Pharmacodynamic Effects on the Central Nervous System of Cholinergic Drugs in Early Phase Drug Development

Investigating potential pharmacodynamic effects in an early phase of central nervous system (CNS) drug research can provide valuable information for further development of new compounds. A computerized and thoroughly validated battery of neuropsychological and neurophysiological tests has been shown to be sensitive to detect drug-induced effects of multiple new and existing compounds. The test battery covers the main CNS domains, which have been shown to respond to drug effects and can be repeatedly administered following drug administration to characterize the concentration-effect profile of a drug.
The standard tests in the battery are saccadic eye movement, smooth pursuit eye movement, the Bowdle visual analog scale (VAS), the Bond and Lader VAS, body sway, adaptive tracking, visual verbal learning, and quantitative electroencephalography (qEEG). However, the test battery is adaptive in nature, meaning that it can be composed and adjusted with tests fit to investigate specific drug classes, or even specific receptors.
Showing effects of new cholinergic drugs designed to have a pro-cognitive outcome has been difficult. The pharmacological challenge model is a tool for early proof-of-pharmacology. Here, a marketed drug is used to induce temporary and reversible disease-like symptoms in healthy subjects, via a pharmacological mechanism related to the disease that is targeted as indication for the new compound. The test battery was implemented to investigate the potential of the nicotinic receptor antagonist mecamylamine to be used as a challenge model for cholinergic dysfunction, as seen in neurodegenerative disorders.
A worsening of scores in a dose dependent manner on the visual verbal learning test (VVLT; a test for learning and memory abilities) and the adaptive tracking test (a measure of visuomotor control and arousal), in particular, showed that the test battery is sensitive to showing acute pharmacodynamic effect after administration of anti-cholinergic drugs.

A validated computerized battery of neuropsychological and neurophysiological tests is used to study pharmacodynamic effects on the central nervous system of newly developed drugs in early phase development. To demonstrate the test battery, the acute effects of mecamylamine and the reversal of these effects by two agonist drugs are described.

Investigating potential pharmacodynamic effects in an early phase of central nervous system (CNS) drug research can provide valuable information for ...

An In Ovo Model for Testing Insulin-mimetic Compounds

Elevated blood glucose levels in type 2 diabetes mellitus (T2DM), a complex and multifactorial metabolic disease, are caused by insulin resistance and &#946;-cell failure. Various strategies, including the injection of insulin or the usage of insulin-sensitizing drugs, were pursued to treat T2DM or at least reduce the symptoms. In addition, the application of herbal compounds has attracted increasing attention. Thus, it is necessary to find efficient test systems to identify and characterize insulin-mimetic compounds. Here we developed a modified chick embryo model, which enables testing of synthetic compounds and herbal extracts with insulin-mimetic properties. Using a fluorescence microscopy-based primary screen, which quantifies the translocation of Glucose transporter 4 (Glut4) to the plasma membrane, we were able to identify compounds, mainly herbal extracts, which lead to an increase of intracellular glucose concentrations in adipocytes. However, the efficacy of these substances requires further verification in a living organism. Thus, we used an in-ovo approach to identify their blood glucose-reducing properties. The approval by an ethics committee is not needed since the use of chicken embryos during the first two-thirds of embryonic development is not considered an animal experiment. Here, the application of this model is described in detail.

An In Ovo Model for Testing Insulin-mimetic Compounds

In this study, we describe an in-ovo system as a promising tool to test insulin-mimetic compounds in a living organism. The main advantages include adequate throughput rates and acceptable costs, which enable the identification of phytochemicals with insulin-mimetic properties.

Elevated blood glucose levels in type 2 diabetes mellitus (T2DM), a complex and multifactorial metabolic disease, are caused by insulin resistance and ...

FM Dye Cycling at the Synapse: Comparing High Potassium Depolarization, Electrical and Channelrhodopsin Stimulation

FM dyes are used to study the synaptic vesicle (SV) cycle. These amphipathic probes have a hydrophilic head and hydrophobic tail, making them water-soluble with the ability to reversibly enter and exit membrane lipid bilayers. These styryl dyes are relatively non-fluorescent in aqueous medium, but insertion into the outer leaflet of the plasma membrane causes a &#62;40X increase in fluorescence. In neuronal synapses, FM dyes are internalized during SV endocytosis, trafficked both within and between SV pools, and released with SV exocytosis, providing a powerful tool to visualize presynaptic stages of neurotransmission. A primary genetic model of glutamatergic synapse development and function is the Drosophila neuromuscular junction (NMJ), where FM dye imaging has been used extensively to quantify SV dynamics in a wide range of mutant conditions. The NMJ synaptic terminal is easily accessible, with a beautiful array of large synaptic boutons ideal for imaging applications. Here, we compare and contrast the three ways to stimulate the Drosophila NMJ to drive activity-dependent FM1-43 dye uptake/release: 1) bath application of high [K+] to depolarize neuromuscular tissues, 2) suction electrode motor nerve stimulation to depolarize the presynaptic nerve terminal, and 3) targeted transgenic expression of channelrhodopsin variants for light-stimulated, spatial control of depolarization. Each of these methods has benefits and disadvantages for the study of genetic mutation effects on the SV cycle at the Drosophila NMJ. We will discuss these advantages and disadvantages to assist the selection of the stimulation approach, together with the methodologies specific to each strategy. In addition to fluorescent imaging, FM dyes can be photoconverted to electron-dense signals visualized using transmission electron microscopy (TEM) to study SV cycle mechanisms at an ultrastructural level. We provide the comparisons of confocal and electron microscopy imaging from the different methods of Drosophila NMJ stimulation, to help guide the selection of future experimental paradigms.

Synaptic vesicle (SV) cycling is the core mechanism of intercellular communication at neuronal synapses. FM dye uptake and release are the primary means of quantitatively assaying SV endo- and exocytosis. Here, we compare all the stimulation methods to drive FM1-43 cycling at the Drosophila neuromuscular junction (NMJ) model synapse.

시 냅 스에서 사이클링 하는 FM 염료: 높은 칼륨 도발은, 전기 및 Channelrhodopsin 자극을 비교

FM dyes are used to study the synaptic vesicle (SV) cycle. These amphipathic probes have a hydrophilic head and hydrophobic tail, making them ...

The Combined Use of Transcranial Direct Current Stimulation and Robotic Therapy for the Upper Limb

Neurologic disorders such as stroke and cerebral palsy are leading causes of long-term disability and can lead to severe incapacity and restriction of daily activities due to lower and upper limb impairments. Intensive physical and occupational therapy are still considered main treatments, but new adjunct therapies to standard rehabilitation that may optimize functional outcomes are being studied.
Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique that polarizes underlying brain regions through the application of weak direct currents through electrodes on the scalp, modulating cortical excitability. Increased interest in this technique can be attributed to its low cost, ease of use, and effects on human neural plasticity. Recent research has been performed to determine the clinical potential of tDCS in diverse conditions such as depression, Parkinson&#39;s disease, and motor rehabilitation after stroke. tDCS helps enhance brain plasticity and seems to be a promising technique in rehabilitation programs.
A number of robotic devices have been developed to assist in the rehabilitation of upper limb function after stroke. The rehabilitation of motor deficits is often a long process requiring multidisciplinary approaches for a patient to achieve maximum independence. These devices do not intend to replace manual rehabilitation therapy; instead, they were designed as an additional tool to rehabilitation programs, allowing immediate perception of results and tracking of improvements, thus helping patients to stay motivated.
Both tDSC and robot-assisted therapy are promising add-ons to stroke rehabilitation and target the modulation of brain plasticity, with several reports describing their use to be associated with conventional therapy and the improvement of therapeutic outcomes. However, more recently, some small clinical trials have been developed that describe the associated use of tDCS and robot-assisted therapy in stroke rehabilitation. In this article, we describe the combined methods used in our institute for improving motor performance after stroke.

The combined use of transcranial direct current stimulation and robotic therapy as an add-on for conventional rehabilitation therapy may result in improved therapeutic outcomes due to modulation of brain plasticity. In this article, we describe the combined methods used in our institute for improving motor performance after stroke.

상 지 대 한 Transcranial 직접 현재 자극과 로봇 치료의 사용

Neurologic disorders such as stroke and cerebral palsy are leading causes of long-term disability and can lead to severe incapacity and restriction of ...

The Evoked Potential Operant Conditioning System (EPOCS): A Research Tool and an Emerging Therapy for Chronic Neuromuscular Disorders

The Evoked Potential Operant Conditioning System (EPOCS) is a software tool that implements protocols for operantly conditioning stimulus-triggered muscle responses in people with neuromuscular disorders, which in turn can improve sensorimotor function when applied appropriately. EPOCS monitors the state of specific target muscles&#8212;e.g., from surface electromyography (EMG) while standing, or from gait cycle measurements while walking on a treadmill&#8212;and automatically triggers calibrated stimulation when pre-defined conditions are met. It provides two forms of feedback that enable a person to learn to modulate the targeted pathway&#39;s excitability. First, it continuously monitors ongoing EMG activity in the target muscle, guiding the person to produce a consistent level of activity suitable for conditioning. Second, it provides immediate feedback of the response size following each stimulation and indicates whether it has reached the target value.
To illustrate its use, this article describes a protocol through which a person can learn to decrease the size of the Hoffmann reflex&#8212;the electrically-elicited analog of the spinal stretch reflex&#8212;in the soleus muscle. Down-conditioning this pathway&#39;s excitability can improve walking in people with spastic gait due to incomplete spinal cord injury. The article demonstrates how to set up the equipment; how to place stimulating and recording electrodes; and how to use the free software to optimize electrode placement, measure the recruitment curve of direct motor and reflex responses, measure the response without operant conditioning, condition the reflex, and analyze the resulting data. It illustrates how the reflex changes over multiple sessions and how walking improves. It also discusses how the system can be applied to other kinds of evoked responses and to other kinds of stimulation, e.g., motor evoked potentials to transcranial magnetic stimulation; how it can address various clinical problems; and how it can support research studies of sensorimotor function in health and disease.

The Evoked Potential Operant Conditioning System EPOCS: A Research Tool and an Emerging Therapy for Chronic Neuromuscular Disorders

The Evoked Potential Operant Conditioning System aids scientific investigation of sensorimotor function and can administer targeted neurobehavioral training that can impact sensorimotor rehabilitation in neuromuscular disorders. This article describes its capabilities and illustrates its application in modifying a simple spinal reflex to achieve lasting improvement in motor function.

유발 된 잠재적 조작 적 컨디셔닝 시스템 (EPOCS) : 만성 신경근 장애에 대한 연구 도구 및 새로운 치료법

The Evoked Potential Operant Conditioning System (EPOCS) is a software tool that implements protocols for operantly conditioning stimulus-triggered muscle ...