1036 lines
80 KiB
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1036 lines
80 KiB
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<meta name="description" content="Demonstration of the feasibility of using a fiberless optoelectrode for activating and recording from neurons… New insights into the mechanisms of neurovascular coupling… Chronic in vivo recordings with carbon fiber microelectrodes… In vivo subcellular imaging of voltage and calcium signals… Newly designed fiberless multi-color optoelectrode for in vivo use" />
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<title>BRAIN Publication Roundup – Fall 2016 | BRAIN Initiative</title>
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<div class="field field--name-field-simple-date field--type-datetime field--label-hidden field__item"><time datetime="2016-12-06T12:00:00Z" class="datetime">December 06, 2016</time>
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<source srcset="/sites/default/files/styles/half_width_medium/public/migrate-images/brain_blue_bg.png?itok=RoSbiDRX 1x" media="all and (min-width: 48em) and (max-width: 61.99em)" type="image/png" width="238" height="188"/>
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<div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p><em>Demonstration of the feasibility of using a fiberless optoelectrode for activating and recording from neurons… New insights into the mechanisms of neurovascular coupling… Chronic in vivo recordings with carbon fiber microelectrodes… In vivo subcellular imaging of voltage and calcium signals…</em></p>
|
||
|
||
<p><strong>Newly designed fiberless multi-color optoelectrode for <em>in vivo</em> use </strong></p>
|
||
|
||
<p>Optogenetics is a promising technology that offers the opportunity to probe the function of the brain at an unprecedented level of cellular and functional specificity. Using different forms of light-sensitive genetic material, it has become possible to target specific cell types within a given region of the brain for modulation. Based on the opsin that is inserted and the wave length of the light used, one has the ability to temporarily activate or inactivate the targeted cell type. As a relatively new technique, optogenetics’ applications are advancing at an accelerated pace, with frequent, elegant solutions to technical challenges. <a href="/glossary?title=BRAIN" class="glossary-tooltip" data-toggle="tooltip" title="The Brain Research through Advancing Innovative Neurotechnologies Initiative aims to accelerate the development and application of innovate technologies to produce a new, dynamic picture of the brain.">BRAIN</a> awardee <a href="http://yoon.eecs.umich.edu/">Dr. Euisik Yoon</a> and colleagues at the University of Michigan recently published an article in <a href="https://www.ncbi.nlm.nih.gov/pubmed/?term=27485264"><em>Scientific Reports</em></a> that details a number of technical advances to their novel optoelectrode. The new electrode uses a combination of injection laser diode (ILD) and gradient-index (GRIN) lenses to achieve a fiberless system that can deliver multiple wavelengths of light to the same brain area. Additionally, this novel recording system protects both tissue and electrode from electrical and thermal damage. As a proof of principle, the researchers demonstrated they could simultaneously record neural activity from the electrodes while stimulating with two different wavelengths of light to both enhance and inhibit neural activity in hippocampal CA1 pyramidal cells in anesthetized mice. This new neural modulatory and recording technology represents an impressive advancement in the field of optogenetics, which will likely lead to new research opportunities and a better understanding of neural network dynamics.</p>
|
||
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||
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|
||
<source srcset="/sites/default/files/styles/full_width_extra_large/public/brain_blog_media/image/fiberless-optoelectrode-image.png?itok=xRR_n4AH 1x" media="all and (min-width: 75em)" type="image/png" width="795" height="392">
|
||
<source srcset="/sites/default/files/styles/full_width_/public/brain_blog_media/image/fiberless-optoelectrode-image.png?itok=s4tisvB8 1x" media="all and (min-width: 62em) and (max-width: 74.99em)" type="image/png" width="660" height="326">
|
||
<source srcset="/sites/default/files/styles/full_width_medium/public/brain_blog_media/image/fiberless-optoelectrode-image.png?itok=75NixLU_ 1x" media="all and (min-width: 48em) and (max-width: 61.99em)" type="image/png" width="480" height="237">
|
||
<source srcset="/sites/default/files/styles/full_width_small/public/brain_blog_media/image/fiberless-optoelectrode-image.png?itok=zklGKQBr 1x" media="all and (min-width: 34em) and (max-width: 47.99em)" type="image/png" width="440" height="217">
|
||
<img loading="eager" src="/sites/default/files/styles/full_width_small/public/brain_blog_media/image/fiberless-optoelectrode-image.png?itok=zklGKQBr" width="440" height="217" alt="The left image shows a schematic of the newly designed optoelectrode, displaying the placement of the injection laser diodes (IDLs) and gradient-index (GRIN) lenses, along with the neural probes. The right image shows the effect of modulating hippocampal CA1 pyramidal cells with either a blue (middle) or red (bottom) light from the same optoelectrode. The activity patterns show clearly distinct responses to both forms of light.">
|
||
|
||
</picture>
|
||
|
||
</div>
|
||
</div>
|
||
|
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</div>
|
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|
||
<figcaption><em>The left image shows a schematic of the newly designed optoelectrode, displaying the placement of the injection laser diodes (IDLs) and gradient-index (GRIN) lenses, along with the neural probes. The right image shows the effect of modulating hippocampal CA1 pyramidal cells with either a blue (middle) or red (bottom) light from the same optoelectrode. The activity patterns show clearly distinct responses to both forms of light.</em></figcaption>
|
||
</figure>
|
||
<p><strong>Cell type-specific contributions to the BOLD signal</strong></p>
|
||
|
||
<p>Understanding the neural underpinnings of the change in blood flow and volume due to neural activity, the hemodynamic response, is critical to fully interpret the findings from fMRI experiments. As such, the study of the relationship between local neural activity and subsequent changes in cerebral blood flow, known as neurovascular coupling, and its association with particular cell types is an important part of the <a href="/glossary?title=BRAIN" class="glossary-tooltip" data-toggle="tooltip" title="The Brain Research through Advancing Innovative Neurotechnologies Initiative aims to accelerate the development and application of innovate technologies to produce a new, dynamic picture of the brain.">BRAIN</a> Initiative®. BRAIN grantee <a href="http://nil.ucsd.edu/index.php?menu=home">Dr. Anna Devor</a> and her team recently published an article in <a href="https://www.ncbi.nlm.nih.gov/pubmed/27244241"><em>eLIfe</em></a> that used a combination of neural recording techniques to determine which cells are actively involved in neurovascular coupling. Using optogenetic modulation and recordings of local neuronal activity with two-photon imaging in mice, the group identified particular mechanisms responsible for vasoconstriction, which is a main component of the blood oxygenation level dependent (BOLD) fMRI signal. Specifically, they found that inhibitory neurons in the cerebral cortex are responsible for vasoconstriction through the release of a signaling molecule, neuropeptide Y (NPY), which acts on NPY-Y1 receptors located on blood vessels in the brain. Excitatory neurons were not involved in vasoconstriction; however, stimulation of either inhibitory or excitatory neurons could lead to vasodilation. To compare the optogenetic stimulation to normal sensory conditions, the researchers recorded from the same region of the somatosensory cortex during forepaw stimulation and optogenetic modulation, stimulation of inhibitory neurons produced a similar effect to sensory stimulation within the same neural tissue. The results of this study shed light on which cell types are responsible for particular components of the BOLD response, and are likely to have an important impact on the interpretation of fMRI studies across species. </p>
|
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<figure role="group" class="caption caption-drupal-media align-center">
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<div class="image full drupal-media-object">
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<div class="field__item"> <picture>
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<source srcset="/sites/default/files/styles/full_width_extra_large/public/brain_blog_media/image/cell-type-specific-image.png?itok=7A72KMde 1x" media="all and (min-width: 75em)" type="image/png" width="795" height="372">
|
||
<source srcset="/sites/default/files/styles/full_width_/public/brain_blog_media/image/cell-type-specific-image.png?itok=aPPr9cT2 1x" media="all and (min-width: 62em) and (max-width: 74.99em)" type="image/png" width="660" height="309">
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<source srcset="/sites/default/files/styles/full_width_medium/public/brain_blog_media/image/cell-type-specific-image.png?itok=Ri_GA_vr 1x" media="all and (min-width: 48em) and (max-width: 61.99em)" type="image/png" width="480" height="225">
|
||
<source srcset="/sites/default/files/styles/full_width_small/public/brain_blog_media/image/cell-type-specific-image.png?itok=VOQVMowl 1x" media="all and (min-width: 34em) and (max-width: 47.99em)" type="image/png" width="440" height="206">
|
||
<img loading="eager" src="/sites/default/files/styles/full_width_small/public/brain_blog_media/image/cell-type-specific-image.png?itok=VOQVMowl" width="440" height="206" alt="The left image shows the position of a diving arteriole that was imaged over the mouse somatosensory cortex. The right image shows the response in this particular arteriole to stimulation of the forepaw (black traces) and a similar response profile when the inhibitory neurons were stimulated optogenetically (red trace). ">
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<figcaption><em>The left image shows the position of a diving arteriole that was imaged over the mouse somatosensory cortex. The right image shows the response in this particular arteriole to stimulation of the forepaw (black traces) and a similar response profile when the inhibitory neurons were stimulated optogenetically (red trace). </em></figcaption>
|
||
</figure>
|
||
<p><strong>New carbon fiber electrodes show long-term stability with minimal damage to the brain</strong></p>
|
||
|
||
<p>One of the goals of the <a href="/glossary?title=NIH" class="glossary-tooltip" data-toggle="tooltip" title="National Institutes of Health - A Federal agency whose mission is to improve the health of the people of the United States. NIH is a part of the Public Health Service, which is part of the U.S. Department of Health and Human Services. ">NIH</a> <a href="/glossary?title=BRAIN" class="glossary-tooltip" data-toggle="tooltip" title="The Brain Research through Advancing Innovative Neurotechnologies Initiative aims to accelerate the development and application of innovate technologies to produce a new, dynamic picture of the brain.">BRAIN</a> Initiative is to develop and apply improved methods for large-scale monitoring of neural activity. Chronic electrophysiological recordings in animal studies, as well as in human studies such as those involving deep brain stimulation and brain machine interface systems, are limited by current electrode technology. NIH BRAIN awardee <a href="http://chestekresearch.engin.umich.edu/">Dr. Cynthia Chestek</a> and her colleagues from the University of Michigan and the University of Pittsburgh recently published a paper in the <a href="https://www.ncbi.nlm.nih.gov/pubmed/?term=27705958"><em>Journal of Neural Engineering</em></a> that assessed a new type of microelectrode array for long-term recordings. To reduce inflammation caused by typical electrodes, Chestek and colleagues have developed a microelectrode that is one-fifth the size of a human hair in diameter, or approximately eight microns. Previously demonstrated to record high quality neural activity, the electrodes are made of carbon fiber, insulated with parylene-c, and the end sites are coated with poly(3,4-ethylenedioxythiophene) (PEDOT), a conductive material. Chestek and her team showed that when chronically implanted, these electrode arrays detected neural activity for at least three months in the motor cortex of rats. Further, these microelectrodes produced significantly less damage to the brain, as measured by glial scarring and neuronal cell counts, compared to commercially available silicon electrodes. Indeed, these carbon fiber arrays have the potential to greatly improve long-term, <em>in vivo</em> recordings for measuring dynamic activity within the brain. </p>
|
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<figure role="group" class="caption caption-drupal-media align-center">
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<div class="image full drupal-media-object">
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<div class="field__item"> <picture>
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<source srcset="/sites/default/files/styles/full_width_extra_large/public/brain_blog_media/image/carbon-fiber-electrodes-image.png?itok=epmspbjR 1x" media="all and (min-width: 75em)" type="image/png" width="636" height="425">
|
||
<source srcset="/sites/default/files/styles/full_width_/public/brain_blog_media/image/carbon-fiber-electrodes-image.png?itok=DKdQBL2t 1x" media="all and (min-width: 62em) and (max-width: 74.99em)" type="image/png" width="636" height="425">
|
||
<source srcset="/sites/default/files/styles/full_width_medium/public/brain_blog_media/image/carbon-fiber-electrodes-image.png?itok=RB6ot3zx 1x" media="all and (min-width: 48em) and (max-width: 61.99em)" type="image/png" width="480" height="321">
|
||
<source srcset="/sites/default/files/styles/full_width_small/public/brain_blog_media/image/carbon-fiber-electrodes-image.png?itok=jZV_P4Dn 1x" media="all and (min-width: 34em) and (max-width: 47.99em)" type="image/png" width="440" height="294">
|
||
<img loading="eager" src="/sites/default/files/styles/full_width_small/public/brain_blog_media/image/carbon-fiber-electrodes-image.png?itok=jZV_P4Dn" width="440" height="294" alt="The top row shows histological images from brain tissue probed with a silicon electrode, while the bottom row shows examples utilizing the newly designed carbon fiber electrode array. The implantation site of the carbon fiber array demonstrates significantly less Iba1 (microglia) and GFAP (astrocyte) expression (indicators of an immune/inflammatory response from tissue damage), and more NeuN (neurons) staining compared to the area around the silicon electrode.">
|
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||
<figcaption><em>The top row shows histological images from brain tissue probed with a silicon electrode, while the bottom row shows examples utilizing the newly designed carbon fiber electrode array. The implantation site of the carbon fiber array demonstrates significantly less Iba1 (microglia) and GFAP (astrocyte) expression (indicators of an immune/inflammatory response from tissue damage), and more NeuN (neurons) staining compared to the area around the silicon electrode.</em></figcaption>
|
||
</figure>
|
||
<p><strong>New insights into <em>in vivo</em> neural processing using voltage and calcium imaging</strong></p>
|
||
|
||
<p>Determining how neural information is processed across synapses <em>in vivo</em> has been a challenge for neuroscientists. In a recent publication in <a href="https://www.ncbi.nlm.nih.gov/pubmed/?term=27264607"><em>Cell</em></a>, <a href="/glossary?title=BRAIN" class="glossary-tooltip" data-toggle="tooltip" title="The Brain Research through Advancing Innovative Neurotechnologies Initiative aims to accelerate the development and application of innovate technologies to produce a new, dynamic picture of the brain.">BRAIN</a> grantee <a href="http://flyvisionlab.weebly.com/">Dr. Thomas Clandinin</a> from Stanford University and colleagues provided important insight into the dynamics of <em>in vivo</em> neural processing. The authors used two-photon imaging of genetically-encoded voltage and calcium indicators to study synaptically-connected axons and dendrites in the visual system of <em>Drosophila</em>. First, the team validated a new voltage indicator, ASAP2f. Specifically, ASAP2f was expressed in individually identifiable neurons in the optic lobe and visually-evoked responses were measured using two-photon microscopy in the awake fly. The team demonstrated that the temporal features of this indicator in response to light were similar to previously recorded electrophysiological responses from these neurons, suggesting that the voltage imaging was an accurate readout of the biological response. Next, the researchers compared subcellular imaging of voltage and calcium signals in the fly optic lobe in response to the same light stimuli. Unlike voltage signals, calcium signaling patterns varied across subcellular compartments in the same cell, with that pattern remaining similar for cells of the same cell type. These results demonstrate the need to cautiously interpret findings based on different types of indicators, as well as the importance of using more than one indicator to provide a more complete representation of information flow between neurons. </p>
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<source srcset="/sites/default/files/styles/full_width_extra_large/public/brain_blog_media/image/voltage-and-calcium-imaging-image.png?itok=d7WHwlP- 1x" media="all and (min-width: 75em)" type="image/png" width="728" height="489">
|
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<source srcset="/sites/default/files/styles/full_width_/public/brain_blog_media/image/voltage-and-calcium-imaging-image.png?itok=O3D15y1_ 1x" media="all and (min-width: 62em) and (max-width: 74.99em)" type="image/png" width="660" height="443">
|
||
<source srcset="/sites/default/files/styles/full_width_medium/public/brain_blog_media/image/voltage-and-calcium-imaging-image.png?itok=DT8pCSlh 1x" media="all and (min-width: 48em) and (max-width: 61.99em)" type="image/png" width="480" height="322">
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<source srcset="/sites/default/files/styles/full_width_small/public/brain_blog_media/image/voltage-and-calcium-imaging-image.png?itok=BLNCIXC3 1x" media="all and (min-width: 34em) and (max-width: 47.99em)" type="image/png" width="440" height="296">
|
||
<img loading="eager" src="/sites/default/files/styles/full_width_small/public/brain_blog_media/image/voltage-and-calcium-imaging-image.png?itok=BLNCIXC3" width="440" height="296" alt="Mapping voltage and calcium responses in four different regions of the same neuron, Tm3 (A). Inconsistent with similar amplitudes of the voltage signals measured in each region (B and D), calcium signals in the cell body and layer M5 were much smaller than those in layers M1 and M10 (C and E).">
|
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<figcaption><em>Mapping voltage and calcium responses in four different regions of the same neuron, Tm3 (A). Inconsistent with similar amplitudes of the voltage signals measured in each region (B and D), calcium signals in the cell body and layer M5 were much smaller than those in layers M1 and M10 (C and E).</em></figcaption>
|
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</figure>
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</article>
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<p>Hear from BRAIN Initiative trainees, learn about new scientific advancements, and find out about recent funding opportunities by visiting The BRAIN Blog.</p>
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