Kavli Blog

In December, the NIH BRAIN Initiative held its third annual BRAIN Initiative Investigators Meeting, gathering experts from around the globe to share their cutting-edge BRAIN-funded research. The attendees spent three days learning about each other’s work, forming new collaborations, and hearing from members of the BRAIN Initiative Alliance. The meeting featured many interesting panel discussions about the direction and implications of BRAIN Initiative research. On the second day of the meeting, a group of ethicists and scientists discussed some of the ethical implications of the technological advances emerging from BRAIN Initiative research. The panel included five members of the Neuroethics Division of the NIH BRAIN Multi-Council Working Group (MCWG), Drs. Christine Grady, Karen Rommelfanger, Rafael Yuste, Khara Ramos, Prof. Hank Greely, as well as Dr. Winston Chiong, a University of California, San Francisco (UCSF) professor and co-investigator on an NIH BRAIN grant. The neuroethics panel focused on defining neuroethics, why it is important to the scientific community, and how the scientific community might address neuroethical implications of their work.

Dr. Christine Grady provided an introduction to the session, discussing what neuroethics entails and how the NIH is working to integrate neuroethics in the BRAIN Initiative. Dr. Grady emphasized that neuroethics is distinct from research ethics and regulatory compliance. That is to say, neuroethics is a combination of both neuroscience and philosophy that explores the unexpected ethical consequences of neuroscience research. To follow up on this point, the director of the National Institute of Neurological Disorders and Stroke, Dr. Walter Koroshetz, spoke about the importance of integrating neuroethics into the BRAIN Initiative’s priorities. Current and future BRAIN Initiative research studies aim to elucidate, and potentially influence, the mechanisms that give rise to consciousness, our innermost thoughts, and our behaviors, thereby prompting novel

The neuroethics panel, with Dr. Rafael Yuste speaking.

social and ethical questions. Because of this, the NIH released a Request for Applications (RFA) to fund research on neuroethical issues associated with neurotechnological advances supported by the BRAIN Initiative. Dr. Koroshetz reminded the audience that unexpected ethical problems can potentially derail cutting-edge science, and neuroethics is a tool for anticipating and navigating ethical issues.



A common theme of the panel was how critical it is for neuroscientists to engage actively with study participants, philosophers, ethicists, and lawyers to continue to ensure that the ethical implications of their research are fully considered. Dr. Chiong described his experience as an ethicist embedded in a neurosurgical research team. He commented that the interdisciplinary nature of neuroscience results in researchers with diverse expertise working together. Though integrating different views can be challenging, the different perspectives can strengthen the work.

Overall, the panel provided attendees with food for thought and information about the neuroethics resources available to them. The audience actively discussed many of the issues raised during the panel and brought up several new issues they felt needed attention as well. Questions ranged from concerns about patient consent and autonomy, animal research ethics, the possible need for neuroethics guidelines to inform development and use of novel neurotechnologies, and how to engage properly with the public on neuroethics. Throughout the session many resources were described, such as individual university ethics offices, the option to consult with the MCWG Neuroethics Division, and expertise available through the International Neuroethics Society. These and other resources can equip scientists to navigate the novel ethical concerns that cutting-edge neuroscience research often raises. The main take–home message, summarized by Mr. Greely, is that neuroscientists should avail themselves of the expertise that neuroethicists offer.

Videocasts will be available for the NIH BRAIN Initiative Multi-Council Working Group and Neuroethics Division meetings on February 14th and February 15th…

The NIH BRAIN Initiative Multi-Council Working Group (MCWG), consisting of representatives from the 10 NIH Institutes and Centers participating in BRAIN, five at-large members, and ex officio representatives from DARPA, FDA, IARPA and NSF, provides ongoing oversight of the long-term scientific vision of the BRAIN Initiative, in the context of the evolving neuroscience landscape. The sixth meeting of the MCWG will occur on Wednesday, February 15th, 2017, at the NIH Porter Neuroscience Research Center (35 Convent Dr., Bethesda, MD 20892). The videocast may be accessed here.

The Neuroethics Division of the MCWG recommends overall approaches for how the NIH BRAIN Initiative might handle issues and problems involving ethics. The third meeting of the Neuroethics Division will occur on Tuesday, February 14th, 2017, at the NIH Porter Neuroscience Research Center (35 Convent Dr., Bethesda, MD 20892). The videocast may be accessed here.

Whole brain mapping of a sensorimotor response in the zebrafish… Novel optogenetics combination to control select cells in deep brain tissue at high resolution… Instability of neurons during stable song behavior in songbirds…

Whole-brain optogenetic mapping of a visual sensorimotor behavior in the larval zebrafish.

Mapping the interactions between neurons across numerous anatomically distinct brain regions is one of the main priorities of the BRAIN Initiative. This will provide a more comprehensive understanding of how the brain works. Previous studies in invertebrate animals, such as the fruit fly and the nematode, established the utility of these smaller model systems for recording and mapping complex interactions of neurons during behaviors. However, scaling up to the larger central nervous systems of vertebrate animals is difficult due to the orders of magnitude increase in cell numbers and complexity. In a recent article published in Cell, Dr. Florian Engert  and colleagues used 2-photon calcium imaging to map neuronal responses across the entire zebrafish brain. First, the researchers created a computational model of sensorimotor responses based on larval zebrafish swimming behaviors elicited by a series of stimuli moving across the whole visual field. Approximately one-hundred thousand neurons can be simultaneously optically imaged in the translucent larval zebrafish brain, allowing investigation of the functional connections between different brain regions responsible for the observed complex swimming behaviors. The researchers found that a great deal of the brain became activated during the optomotor response to the motion stimuli. Comparison of the activity recorded within a given region of the brain to the computational model provided a neurological map of how the visual sensory signal is transformed into a motor output. By combining these models with a series of lesion experiments, the researchers confirmed that particular regions, including retinal arborization field 6, the pretectum, and posterior commissure, were necessary for the sensorimotor transformation. The use of whole-brain neuronal imaging within ever larger vertebrate model systems will enhance our ability to explore interactions between brain regions during increasingly complex behaviors.

A) A dorsal view of the anatomy of the zebrafish larva. The labels represent the major anatomical regions of the zebrafish brain. B) The activity of all the imaged neurons in relation to the direction of the motion stimulus. The colors represent the preferred direction of each of the cells, as described by the circle in the bottom right.

Establishing stimulation parameters for red-shifted opsin, ReaChR, using 2-photon imaging to control cellular activity in deep brain structures.

Optogenetics, which enables activation or inhibition of select neurons via genetically incorporated light-sensitive ion channels, has dramatically enhanced our understanding of the brain in a short period of time. To date, use of this technology has been limited to relatively superficial brain tissue, due to increased scattering of light within deep brain structures. Recent efforts suggest that red-shifted opsins that react to longer wavelengths of light may help overcome this technical challenge. BRAIN awardees Drs. Hongkui Zeng and Valentina Emiliani pioneered work combining 2-photon stimulation with the red-shifted channelrhodopsin, ReaChR. In their Frontiers in Cellular Neuroscience article, the research team characterized stimulation parameters using an amplified laser for 2-photon holographic stimulation of ReaChR in cultured cells in vitro, as well as in mouse visual cortex neurons in vivo. After achieving nanoampere-scale current generation by stimulating ReaChR, the group illustrated reliable action potential (AP) generation following 15-micrometer diameter light stimulation for 10-milliseconds to neurons expressing ReaChR. To manage latency and variability in AP generation, the investigators found that increasing the laser power density by a factor of 1.5 consistently elicits an AP with millisecond temporal resolution. Finally, the researchers successfully evoked repeated AP trains in ReaChR-expressing pyramidal and fast-spiking cells using 10 light pulses at a range of frequencies. This first demonstration of control of AP generation via 2-photon stimulation of red-shifted ReaChR with high spatial and temporal resolution offers a novel method to control targeted cells in deep brain circuits.

A) Expression of ReaChR opsin in mouse brain slice 2 weeks after viral injection. B) 2-photon microscopy of ReaChR in mouse visual cortex, 7-weeks after viral injection. D) Action potential evoked by 15-micrometer diameter 2-photon holographic stimulation (10 ms) of ReaChR expressing mouse cortical neuron.

Excitatory neurons display variable activity during stable song production in zebra finches.

Recording neural activity over long periods of time to determine how circuit activity gives rise to behavior is an important goal of the BRAIN Initiative. BRAIN awardee Dr. Timothy Gardner  and his laboratory recently developed minimally invasive carbon fiber arrays for long-term neural recordings. In an article in Nature Neuroscience, Dr. Gardner and his team used the carbon fiber arrays, as well as newly designed head-mounted, miniature fluorescence microscopes, to study neural activity in conjunction with song production in zebra finches. The song of the zebra finch exemplifies a stable behavior, where the precise timing and acoustic structure of a song is well-maintained, making it a useful model for studying dynamic neural activity during a stereotyped action. The team recorded from the premotor nucleus, called the HVC, which contains inhibitory interneurons and several classes of excitatory projection neurons. In previous experiments, activity of multi-unit ensembles, or local field potentials (LFPs), was stable over minutes and hours during song production. In these sets of experiments, Dr. Gardner and his team showed that during song, the activity of LFPs, and that of single-unit, inhibitory neurons, were highly stable over the course of days, weeks, and/or months. In contrast, individual, excitatory projection neurons exhibited unstable activity over the course of days. Thus, the song motor pattern in the zebra finch and the activity of the HVC on the regional scale (i.e., LFPs) remained consistent, whereas individual excitatory projection neurons in the HVC drifted in activity patterns, including the probability of their bursting activity, and the likelihood of firing at all, during song. This study used novel recording and imaging techniques to demonstrate an important distinction between multi-unit and single-unit neural activity, as well as inhibitory versus excitatory neuronal activity, during a stable behavioral action.

A) Images of song-related premotor nucleus neuronal activity, false-colored by the timing of max pixel intensity across 5 days for one songbird (top) and 4 days for a second songbird (bottom). B) Trial-averaged activity from all song-related neurons from 1 songbird, plotted over the course of five consecutive days. C) For the same animals shown in A), cells active on 3 consecutive days are combined into a single image in which color indicates neuron participation rather than timing (red = day 1, green = day 2, blue = day 3). Cells with activity on all 3 days appear in white. D) Electrophysiological recording of a projection neuron reveals a new song-related burst, which emerged over the course of 1 day. The blue arrows indicate the trials plotted at the bottom.

Advances in neurotechnology are aimed at helping us better understand normal brain function and how to treat dysfunction associated with brain disorders. These technological advances carry potentially profound ethical implications. A set of recently published articles highlight how the NIH BRAIN Initiative is working to integrate neuroethics in neurotechnology research and development.

Despite being a relatively new effort, research funded under the NIH BRAIN Initiative already is producing new technologies and methods that push the envelope on our ability to record and modulate brain activity. These advances are exciting glimpses of the future of neuroscience and hold promise to deliver new ways to diagnose, treat, and even prevent brain disorders. At the same time, because the brain gives rise to our innermost thoughts, our most basic human needs, and consciousness, brain research raises important social and ethical questions that merit thoughtful consideration.

Two recent papers explore how the NIH BRAIN Initiative, and some of its international counterparts, are aiming to address the ethical issues associated with the research supported by these national brain projects. Hank Greely  and Dr. Christine Grady , co-chairs of the NIH BRAIN Multi-Council Working Group Neuroethics Division (formerly Neuroethics Workgroup), along with Dr. Khara Ramos, Executive Secretary of the Division, published Neuroethics in the Age of Brain Projects as part of the Society for Neuroscience’s special issue of Neuron, focusing on the BRAIN Initiative’s and the European Union Human Brain Project’s neuroethics activities. The article details many of the ongoing efforts from the BRAIN Initiative, including the establishment of a Neuroethics Division within the NIH BRAIN Multi-Council Working Group that serves as a resource to help navigate ethical issues associated with BRAIN research. The Neuroethics Division works with NIH BRAIN Initiative leadership to provide input on ethical issues, consult on research projects as requested, and collaborate on workshops and whitepapers focused on particular neuroethics topics. Underscoring the emphasis on neuroethics within the BRAIN Initiative, NIH has recently released a Request for Applications associated with the BRAIN Initiative to support neuroethics research (applications are due January 30, 2017). This funding opportunity aims to address core ethical issues associated with research focused on the human brain and resulting from advances in neurotechnology supported by the BRAIN Initiative. Neuroethics in the Age of Brain Projects concludes that as neuroscience research efforts grow, so too must grow neuroethics.

The second article is a commentary piece in Cell by Drs. Sara Goering  and Rafael Yuste , arguing for a set of ethical guidelines in the area of neurotechnology research, development, and application. The commentary focuses on how novel neurotechnologies “…will provide access to the core mechanisms that underlie human identity, memories, emotions, personality and, more generally, our minds.” Therefore, the authors argue for composing a framework to guide development and use of neurotechnologies in a way that is consistent with core societal and human values. They also point to the efforts of the NIH BRAIN Multi-Council Working Group Neuroethics Division and the broader neuroethics community to address these issues early on. Importantly, Goering and Yuste emphasize the value of integrating bioethicists with neuroscience researchers involved in the development of any new technologies. They highlight a recent meeting at Columbia University’s NeuroTechnology Center, supported by the Kavli Foundation, which brought together ethicists and neuroscientists to discuss how novel neurotechnologies affect concepts of identity, agency, and normality. A recent post  at Theneuroethicsblog.com summarizes discussions from the meeting.

Taken together these articles highlight the need for neuroethicists and neuroscience researchers to critically evaluate the implications of new advances in neurotechnologies. Importantly, they also show how programs like the BRAIN Initiative are taking these implications seriously and are actively working with researchers to navigate them.

NIH announces three new Requests for Applications (RFAs) for interdisciplinary projects using advanced and innovative technologies to address overarching principles of circuit function in the context of specific brain systems and behaviors. Funding from these new RFAs will enable investigators to unlock the mystery of how complex patterns of neural activity give rise to our thoughts, feelings, and behaviors, and will lay the groundwork for understanding circuit dysfunctions in brain diseases.

In 2014 and 2015, NIH issued Requests for Applications (RFAs) for “Integrated Approaches to Understanding Circuit Function in the Nervous System,” resulting in 17 awards totaling $17 million per year, with each award lasting three years. The short-term goal of this program has been to foster a set of interdisciplinary team projects for understanding the functions of specific circuits in the nervous system, in preparation for a second phase to start in Fiscal Year (FY) 2017.  NIH now announces the second phase of this program with three new Funding Opportunity Announcements (FOAs), each soliciting projects of different size and scope.

RFA-NS-17-018 Team-Research BRAIN Circuit Programs (BCP)

Using the U19 activity code for large, multi-component, interdisciplinary team science programs, this RFA supports research teams drawn either from prior BRAIN-supported projects or from new teams within the greater research community, using advanced and innovative technologies to examine circuit functions related to behavior. Proposals should address overarching principles of circuit function in the context of specific brain systems, such as sensation, perception, emotion, motivation, cognition, choosing, and taking action. Experiments are expected to be guided by explicit theories of circuit function, and to test and update predictive models, by controlling stimuli and behavior while actively recording and manipulating relevant dynamic patterns of neural activity. For this 5-year award with possibility of competing renewal, a Data Science Core is required, and applicants must manage their data and analysis methods in a standardized framework to be developed and used in the project. The application receipt date for this FOA is March 1, 2017. A second receipt date, October 17, 2017, will support awards in FY 2018.

RFA-NS-17-014 Targeted BRAIN Circuits Projects (R01) and RFA-NS-17-015 Exploratory Targeted BRAIN Circuits Projects (R21)

This complementary pair of FOAs seek applications proposing innovative approaches that are in an earlier stage of development or of smaller scale than sought by the larger team-science RFA-NS-17-018. Projects may be from individual labs or multi-PI teams. Proposals should specify tractable research goals to address circuit contributions to behaviors or neural systems using advanced and innovative technologies. Note that the maximum R01 project period (NS-17-014) is 5-years, while the R21 project period (NS-17-015) supports 2-year exploratory projects to establish feasibility and supporting data for potential, subsequent R01 funding.  The application receipt date for both FOAs is March 8, 2017.

Please visit our Active Funding Opportunities page for more details on these and other RFAs for the BRAIN Initiative.

The 2016 BRAIN Initiative Principal Investigators Meeting will occur December 12-14 in Bethesda, Maryland…

The 3rd Annual BRAIN Initiative Investigators Meeting is scheduled for this Monday, December 12th through Wednesday, December 14th, 2016, and will be held at the Bethesda North Marriott Hotel and Conference Center. This meeting will convene BRAIN Initiative awardees, staff, and leadership from the contributing federal agencies (NIH, NSF, DARPA, IARPA, FDA, DOE), plus representatives and investigators from participating non-federal organizations, and members of advocacy groups, the media, public, and Congress. The purpose of this meeting is to provide a forum for discussing exciting scientific developments and potential new directions, and to identify areas for collaboration and research coordination.

The meeting’s website, agenda, and other materials are available here. Registration is available on-site. Live-stream videocasting is also available for plenary sessions on each day of the meeting:

Enjoying the meeting? Tell us about it on Twitter: #studyBRAIN

If you have any additional questions, please contact us at BrainInitiativeConferences@mail.nih.gov

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

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. BRAIN awardee Dr. Euisik Yoon and colleagues at the University of Michigan recently published an article in Scientific Reports 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.

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.

Cell type-specific contributions to the BOLD signal

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 BRAIN Initiative®. BRAIN grantee Dr. Anna Devor and her team recently published an article in eLIfe 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.

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). 

New carbon fiber electrodes show long-term stability with minimal damage to the brain

One of the goals of the NIH BRAIN 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 Dr. Cynthia Chestek and her colleagues from the University of Michigan and the University of Pittsburgh recently published a paper in the Journal of Neural Engineering 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, in vivo recordings for measuring dynamic activity within the brain.

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.

New insights into in vivo neural processing using voltage and calcium imaging

Determining how neural information is processed across synapses in vivo has been a challenge for neuroscientists. In a recent publication in Cell, BRAIN grantee Dr. Thomas Clandinin from Stanford University and colleagues provided important insight into the dynamics of in vivo 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 Drosophila. 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.

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).

The NIH recently announced the 108 newly funded awards for Fiscal Year (FY) 2016 for the NIH BRAIN Initiative®. The NIH will highlight these funded awards, funding opportunities, and other BRAIN-related endeavors, such as The BRAIN Initiative Alliance, at the upcoming, annual Society for Neuroscience conference in San Diego, CA (Nov. 12th-16th, 2016).

With the addition of 108 FY16 funded awards, the current total (FY14-FY16) of NIH-supported BRAIN Initiative research projects is 233, conducted by over 400 investigators across more than 140 performance sites in 13 countries.

The FY16 BRAIN-funded projects by topic, and the number of funded awards per topic, include:

  • Large Scale Recording and Modulation (30)
    • New Technologies/Optimization
    • New Concepts & Early Stage Research
  • Non-Invasive Neuromodulation (16)
  • Foundations/Next-Generation Human Imaging (12)
  • Next-Generation Human Invasive Devices (8)
  • Tools for Cells and Circuits (9)
  • Research Opportunities (7)
  • Technology Sharing/Propagation (6)
  • Theories, Models, Methods (20)

On Sunday, November 13th, at the upcoming annual Society for Neuroscience meeting in San Diego, CA, the NIH will present a dynamic poster (#26.12SU) that will highlight scientific advancements, funding opportunities, and the myriad partnerships that constitute NIH’s contribution to the BRAIN Initiative.

Further, The BRAIN Initiative Alliance, which seeks to inform and engage the public and the scientific community about successes emerging from the BRAIN Initiative, as well as opportunities for further discovery, is launching a new, interactive, website. Additionally, the group will host a satellite event on November 14th, BRAIN Initiative “TAD Talks:” Technology Accelerating Discovery. The event is being co-organized by Dr. Frances Jensen (UPenn) and Dr. Jane Roskams (UBC), and is sponsored via in-kind support by The BRAIN Initiative Alliance (including NIH), with a reception sponsored by The Kavli Foundation. The agenda includes exciting, brief talks from BRAIN Initiative investigators and a panel discussion about the unique opportunities the Initiative provides for the broader scientific community. This is a public event that does not require registration to the Society for Neuroscience meeting.

With four new Requests for Applications (RFAs), NIH announces the formation of the BRAIN Initiative Cell Census Network (BICCN), a resource to be used widely by the neuroscience community that supports a mouse brain atlas, collaboratories for human and non-human primate brains, and a data center.


NIH’s first efforts towards surveying brain cell types were initiated in 2014, with diverse pilot cell classification strategies in a variety of species (for more information on the awards, see the “Census of Cell Types” here). With the following new Funding Opportunity Announcements (FOAs), NIH establishes the BRAIN Initiative Cell Census Network (BICCN), for a systematic generation of comprehensive reference cell census data and relevant tools. The application receipt dates for all four FOAs is January 23, 2017.

  • RFA-MH-17-225 BICCN Comprehensive Mouse Brain Cell Atlas Center

This FOA will support a Comprehensive Center or Centers for a 3D brain cell reference atlas encompassing molecular, anatomical, and physiological annotations of brain cell types in mouse, and to incorporate cell-specific targeting approaches and tools to facilitate this goal.

  • RFA-MH-17-230 Specialized Collaboratory for Mouse Brain Cell Atlas

This FOA will support a group of Specialized Collaboratories to complement the output of the Comprehensive Center(s). NIH expects each Specialized Collaboratory to focus on one or more of the following: (1) molecular signatures such as transcriptional, proteomic, and epigenetic information; (2) anatomy, including cell morphology and anatomical connectivity; (3) functional measures, such as electrophysiology or assays of functional connectivity; (4) cell specific targeting, including development of novel tools, advanced approaches, or essential information for accessing and manipulating brain cell types.

  • RFA-MH-17-210 BICCN Specialized Collaboratory for Human and Non-Human Primate Brain Cell Atlases

This FOA will support specialized collaboratories to adopt scalable technology platforms and workflows towards reference cell atlases of human and other primate brains. The size, complexity, and variability of primate brains confer unique challenges that these collaboratories will address for the future. Collaboratories may focus on one or a few select brain regions, and are expected to develop and assess scalable and multiplexed approaches for comprehensive cell type surveys.

This FOA solicits applications for a single center to coordinate data from the BICCN and other interested researchers to establish a web-accessible information system, which will store, analyze, curate, and display all data and metadata on brain cell types and their connectivity. The Cell Data Center is expected to lead efforts to (1) establish spatial and semantic standards, (2) register multimodal brain cell census data to common brain coordinate systems, (3) create searchable digital brain atlases for cell census data, and (4) form a unified and comprehensive brain cell knowledge base that integrates existing brain cell census data and associated information.

The funded projects will be coordinated by NIH staff to build a brain cell census resource that can be widely used throughout the research community. The BICCN will create and maintain fundamental knowledge on cell types and their organizational logic within brain circuits and will provide an open-access 3D reference atlas of the mouse brain, including molecular, anatomical, and physiological annotations, along with pilot data from larger brains. Other goals for the BICCN include reagents for cell-specific targeting and validation of high-throughput, low-cost approaches to enable new research characterizing cell diversity in healthy and diseased brains of multiple species.

Please visit our Active Funding Opportunities page for more details on these and other RFAs for the BRAIN Initiative.