Image: Immunofluorescent stains for neurons (NeuN; green), astrocytes (GFAP; red), and cell nuclei (DAPI, blue) in the hippocampal CA3 region of brains either unperfused for 10 hours after death (left) or subjected to perfusion with the BrainEx technology (right). After 10 hours postmortem, neurons and astrocytes normally undergo cellular disintegration unless salvaged by the BrainEx system.
NINDS/NIMH Press Release (April 17, 2019):
Article: Vrselja Z et al., Restoration of brain circulation and cellular functions hours postmortem. Nature. April 18, 2019.
Image: High-speed, volumetric SCAPE microscopy was used to capture the activity of proprioceptive neurons inside freely moving Drosophila larvae. The high-resolution imaging approach allowed researchers to view a continuum of sensory feedback from proprioceptive neurons during forward crawling and exploratory head movements. Central structure (in pink) is the larva’s ventral nerve cord.
No NINDS Press Release, but BRAIN Publication RoundUp:
Article: Vaadia RD et al., Characterization of Proprioceptive System Dynamics in Behaving Drosophila Larvae Using High-Speed Volumetric Microscopy. Current Biology. March 18, 2019.
NINDS and other NIH Institutes including NIA, NIMH, and NHGRI, are invested in tackling Alzheimer's Disease (AD) and AD-related dementias. Recently, researchers interrogated the molecular and cellular basis of Alzheimer's disease using single-cell transcriptomic analysis. They analyzed over 80,000 single-nucleus transcriptomes from the prefrontal cortex of 48 individuals with varying degrees of AD pathology. Disease-related changes appeared early in pathological progression and were often cell-type specific, whereas late stage changes occurred across all cell types. Myelination-related processes were consistently altered across cell types, suggesting a key role for myelination in AD pathophysiology.
Image: Immunohistochemistry on oligodendrocytes in the white matter of Brodmann area 10 for individuals with no AD pathology (top row) or AD pathology (bottom row). These cell subtypes expressed high levels of QDPR and CRYAB. The latter is an anti-apoptotic and neuroprotective chaperone, the dysfunction of which could exacerbate inflammation and demyelination.
No NINDS Press Release
Article: Mathys H et al., Single-cell transcriptomic analysis of Alzheimer's disease. Nature. June 2019. https://pubmed.ncbi.nlm.nih.gov/31042697-single-cell-transcriptomic-analysis-of-alzheimers-disease/
Researchers at the Allen Institute for Brain Science used single-nucleus RNA-sequencing analysis to perform a comprehensive study of cell types in middle temporal gyrus of human cortex. Comparison of this human cortex to similar mouse cortex datasets revealed well-conserved cellular architecture that enabled matching of homologous types and predictions of properties of human cell types. However, there were also extensive differences between homologous human and mouse cell types, including marked alterations in proportions, laminar distributions, gene expression and morphology. Despite cellular properties that were conserved across species, species-specific features emphasize the importance of directly studying human brain.
Image: (left panel) A visualization of human (blue) and mouse (orange) inhibitory neuron clusters, demonstrating a surprising degree of conservation across species. (right panel) Divergent cell-type expression is shown through expression of serotonin receptors across human (top) and mouse (bottom).
No NINDS Press Release
Article: Hodge RD et al., Conserved cell types with divergent features in human versus mouse cortex. Nature. September 5, 2019. https://pubmed.ncbi.nlm.nih.gov/31435019-conserved-cell-types-with-divergent-features-in-human-versus-mouse-cortex/
Image: Immunofluorescent image of nociceptive basolateral amygdala (BLA) neurons (red) that were re-activated (c-Fos; green) following a second pin prick to the paw (left). Once identified, these neurons were silenced using chemogenetics. Neurons expressing ChR2-eYFP (green) in peripheral nociceptors (red) of dorsal root ganglia of the spinal cord (right).
Article: Corder G et al., An amygdalar neural ensemble that encodes the unpleasantness of pain. Science. January 18, 2019.
Image: Fluorescent image of mouse cortical neurons expressing the varenicline receptor PSAM4-GlyR (EGFP; green) with intact cell surface (red) (left). Varenicline (10nM) suppressed the firing of these neurons in vitro (right).
Article: Magnus CJ et al., Ultrapotent chemogenetics for research and potential clinical applications. Science. April 19, 2019.
Image: An NIH-funded clinical trial - Systolic Blood Pressure Intervention Trial (SPRINT) - found a link between blood pressure and white matter lesions. Arrows highlight examples of lesions seen on magnetic resonance imaging brain scans.
NIH News Release (August 13, 2019):
Article: Nasrallah, IM et al., Association of intensive vs standard blood pressure control with cerebral white matter lesions. Jama. August 13, 2019.
Image: Immunofluorescent image of gut tissue stained for pSer129-a-syn (green) and Tuj-1 (red) – indicators of alpha-syn presence – in the upper duodenum (UD) and pyloric stomach (PS) one-month after alpha-syn injection (top). Photomicrographs from mesencephalon sections containing dopamine (TH-positive) neurons in the substansia nigra pars compacta region seven months after alpha-syn injection into the guts of a healthy (left), vagotomized (middle), and alpha-syn knockout mouse (right) (bottom).
Image: Fluorescent image of synaptic connections between gliomas and neurons in a mouse brain. White box and arrows highlight a region with dense synaptic connections. Green denotes neurofilament (axon); white denotes glioma cell processes; blue denotes synapsin (presynapse); red denotes glioma postsynaptic puncta.
Article: Venkatesh, HS et al., Electrical and synaptic integration of glioma into neural circuits. Nature. September 26, 2019.
Image: Images showing increased neuronal AT8 immunoreactivity – a marker of increased tau phosphorylation – in the piriform cortex of mice on a normal (ND) and high-salt (HSD) diet. Right images are magnified views of the white boxes on the left.
NIH News Release (October 23, 2019):
Article: Faraco, G et al., Dietary salt promotes cognitive impairment through tau phosphorylation. Nature.
The end of a decade – and the start of a new one – brings a certain state of reflection that can differ from the usual year-to-year perspective. As I look back on the last decade, and particularly in the last year, I am heartened and encouraged by the significant strides that NINDS has made and continues to make through funding awards, facilitating collaborations, launching new initiatives, and transitioning leadership roles. With gratitude, we thank our investigators, research subjects, and our partners representing those suffering from neurological disorders and stroke.
In 2019, NINDS launched its next strategic planning effort, led by NINDS Deputy Director Dr. Nina Schor, which will help to set overarching goals for the institute to achieve in the next 5-10 years. For this effort, we aim to tune our practices and policies to our vision and mission, in order to better serve and anticipate the needs of the research and patient communities and the public. We want to dream big! As a first step for this process, we conducted an initial request for information (RFI) to inform the roadmap by which internal NINDS taskforces will collaborate with both internal and external stakeholders. While the RFI submission deadline has passed, we continue to monitor submissions and want to hear from you! Please also continue to follow along as we post new opportunities for engagement during the strategic planning process.
One of the biggest 2019 accomplishments was the announcement of the awards for the Helping to End Addiction Long-term Initiative, or NIH HEAL Initiative, investing $945M in research across approximately 375 awards in 41 states. The HEAL Initiative presents an unprecedented opportunity to advance the field of pain research and reduce reliance on opioid medications. As the lead institute for pain research at NIH, NINDS helped to develop the pain management pillars of the Initiative and will serve as the hub for several programs to accelerate the development of new therapies. One notable program is the Early Phase Pain Investigation Clinical Network (EPPIC-Net) which provides the infrastructure and clinical population for early stage clinical trials to test non-addictive pain therapies. Applications for trials to be conducted in EPPIC-Net are open and evaluated on a rolling basis. As NIH staff have worked tirelessly to ensure the quick launch of these awards, I thank them and am eager to follow the progress of these programs to improve pain management and outcomes through research.
At its halfway point, the BRAIN Initiative is revolutionizing neuroscience research. Since 2014, NIH has invested over $1.3 billion in the BRAIN Initiative, supporting over 700 awards to hundreds of investigators. These awards leverage broad scientific disciplines and both investigator- and team-based science towards addressing fundamental questions in neural circuit function, and to date, hundreds of publications have generated new tools and neurotechnologies that better help us see the brain in action. Numerous events, including most recently at the 2019 Annual Meeting of the Society of Neuroscience, highlighted the game-changing nature of these tools and resources, as they begin to be distributed to the wider basic neuroscience community and impact clinical research.
As the NIH BRAIN Initiative moves toward its second half, I am thrilled it is doing so under the leadership of Dr. John Ngai, recently appointed as NIH BRAIN Initiative Director, who will join the NIH team in March. Dr. Ngai is currently the Coates Family Professor of Neuroscience at the University of California, Berkeley, and has built a long-standing research program on how the nervous system detects odors and turns them into neural signals sent to the brain. He will oversee both day-to-day operations and BRAIN’s long-term strategy, which is informed by two recently accepted reports on the progress and emerging opportunities in neuroscience, led by Drs. Catherine Dulac and John Maunsell, and neuroethics, led by Drs. Jim Eberwine and Jeff Kahn, for the Initiative. I thank both working groups for their diligent efforts in this strategic planning process over the last year and a half, and with their discussions and under the helm of Dr. Ngai, I am excited for what scientific advances from BRAIN are just around the corner.
Another notable 2019 accomplishment is the launch of the Accelerating Medicines Partnership (AMP) Parkinson’s Disease (PD) Knowledge Portal. This platform will enable new PD biomarkers to come to fruition by enabling access to harmonized longitudinal clinical and -omics data from over 4000 participants, including both individuals with PD and healthy controls. We also continue our robust collaboration with the National Institute on Aging to fund research in Alzheimer’s disease (AD) and Alzheimer’s disease-related dementias (ADRD). In March, NINDS hosted the triennial ADRD Summit to review and update priorities and timelines for addressing the ADRDs—including frontotemporal (FTD), Lewy body (LBD), mixed, and vascular dementias. Those updates will guide NIH investments in ADRD research, and we are grateful to the many stakeholders who have participated in the planning process.
Conducting the best science goes hand in hand with empowering the next generation of scientists, and so I am thrilled that NINDS recognizes outstanding mentors through the Landis Award for Outstanding Mentorship. In making the second year of awards this past summer, we want the community to know just how important mentorship is for sustaining the scientific research enterprise. To achieve our research and scientific goals, both at NINDS and at NIH as a whole, it truly is imperative that we value the efforts of outstanding mentors and lift up a diverse range of individuals to position them for success. Toward that end, I made a commitment earlier this year along with Francis Collins to only give presentations at conferences where diversity and inclusion are actively considered in panels or other prominent speaking slots, as diversity is not only important for representation, but also for making the science better.
As a step in making that science better, I also want to emphasize the utmost importance in maintaining healthy workplace climates, both here at NINDS and in the research environments that we support. Here at NINDS and at NIH, we are coming to grips with cultures and environments that have permitted unacceptable behavior for too long. To do better, we are taking action. Dr. Collins created a Working Group of the Advisory Committee to the NIH Director on Changing the Culture of Sexual Harassment, and NINDS is organizing a series of town halls early in 2020 that will be mandatory for all staff. There is no easy answer to addressing this issue, but it is critical that we work together to foster a culture of respect for all.
In 2019, NINDS supported innovative scientific advances in neuroscience and neurology. While I cannot highlight all of them here, I have selected a few favorites that you can view above. The past also brought us opportunities to explore and build new research programs, collaborations, and partnerships. All of our efforts at NINDS move forward (in no small part), thanks to our leadership team. In February, Dr. Lorna Role joined NINDS as Scientific Director, bringing her pioneering research and broad leadership experience to direct the intramural program (IRP), which includes 48 labs and 1000+ staff. Dr. Role has studied the brain’s cholinergic system over the lifespan, been the principal investigator on numerous NIH-funded grands, and earned numerous awards and honors including the NIH Director’s Pioneer Award. Under the guidance of strong NINDS leaders, we are poised for even more progress in 2020. In this new decade, which begins with a 7.8% increase in Congressionally appropriated funding over last year, we continue our important mission: seeking fundamental knowledge about the nervous system and using that knowledge to reduce the burden of neurological disease.