For all the latest news from the Solomon H. Snyder Department of Neuroscience
For all the latest news from the Solomon H. Snyder Department of Neuroscience
Jonathan Grima, a Neuroscience Graduate Student in Dr. Jeffrey Rothstein's lab, recently reported his research in Neuron regarding a potential cellular cause for neurodegenerative diseases like Huntington's Disease. Jonathan, and his work, were also featured in a recent Baltimore Sun article.
Publications from Primary Faculty Members - April 2017:
Pouget P, Murthy A, Stuphorn V. Cortical control and performance monitoring of interrupting and redirecting movements. Philos Trans R Soc Lond B Biol Sci. 2017 Apr 19;372(1718). pii: 20160201. doi: 10.1098/rstb.2016.0201.
Congratulations to Neuroscience Graduate students Althea Cavanaugh, David Ottenheimer, and Cody Call who have each been awarded a National Science Foundtation Graduate Research Fellowship for 2017!
The NSF Graduate Research Fellowship Program recognizes and supports outstanding graduate students in NSF-supported science, technology, engineering, and mathematics disciplines who are pursuing research-based Master's and doctoral degrees at accredited United States institutions.
In a recent issue of Neuron, Agarwal et al. (2017) report that calcium efflux from mitochondria during brief openings of the mitochondrial permeability transition pore (mPTP) contribute to calcium microdomains.
SiYing (Sally) Li, a first year graduate student in the Department of Neuroscience, has been selected as the recipient of the 2016-2017 Fred and Ruth Kort Young Scholar Fund. Fred and Ruth Kort Young established this award to support outstanding first-year graduate students.
Publications from Primary Faculty Members - March 2017:
Chiu SL, Diering GH, Ye B, Takamiya K, Chen CM, Jiang Y, Niranjan T, Schwartz CE, Wang T, Huganir RL. GRASP1 Regulates Synaptic Plasticity and Learning through Endosomal Recycling of AMPA Receptors. Neuron. 2017 Mar 8. pii: S0896-6273(17)30139-3. doi: 10.1016/j.neuron.2017.02.031. [Epub ahead of print]
Cox E, Hwang W, Uzoma I, Hu J, Guzzo C, Jeong J, Matunis M, Qian J, Zhu H, Blackshaw S. Global analysis of SUMO-binding proteins identifies SUMOylation as a key regulator of the INO80 chromatin remodeling complex. Mol Cell Proteomics. 2017 Mar 2. pii: mcp.M116.063719. doi: 10.1074/mcp.M116.063719. [Epub ahead of print]
Gao M, Whitt JL, Huang S, Lee A, Mihalas S, Kirkwood A, Lee HK. Experience-dependent homeostasis of 'noise' at inhibitory synapses preserves information coding in adult visual cortex. Philos Trans R Soc Lond B Biol Sci. 2017 Mar 5;372(1715). pii: 20160156. doi: 10.1098/rstb.2016.0156.
Li Z, Tseng PY, Tiwari V, Xu Q, He SQ, Wang Y, Zheng Q, Han L, Wu Z, Blobaum AL, Cui Y, Tiwari V, Sun S, Cheng Y, Huang-Lionnet JH, Geng Y, Xiao B, Peng J, Hopkins C, Raja SN, Guan Y, Dong X. Targeting human Mas-related G protein-coupled receptor X1 to inhibit persistent pain. Proc Natl Acad Sci U S A. 2017 Mar 7;114(10):E1996-E2005. doi: 10.1073/pnas.1615255114. Epub 2017 Feb 21.
It is a puzzle that troubles the field for many years that how pain and itch, two closely related sensations (once thought as one sensation), are differentiated by the nervous systems. Coding of pain and itch are heatedly debated for decades. The current specificity theory suggests that these two kinds of signals are carried by separate pathways, with some interactions, for example pain can inhibit itch and that explains why we all scratch to inhibit pain. It is true in the periphery (our previous study indicate a small population of neurons in the periphery only codes for itch sensation), but a study from our lab suggests that there could be more crosstalk between these two sensations in the central than we expected. People might not notice in real life, but in human psychophysical studies, well-isolated experimental environments, when human subjects are given itchy substances, they typically report intense itch sensations accompanied by minor noxious sensations, such as pricking, stinging and burning. Our new leaky gate model suggest in certain circumstances intense itch signals can trigger minor pain sensations, which can explain such phenomenon.
Chronic pain is a major health and economic problem worldwide with an estimated prevalence reaching epidemic levels of >25% of the population. For example in the US, chronic pain affects over 116 million adults and costs up to $635 billion annually in treatment and lost productivity. Most drugs on the market for chronic pain have undesired side effects because their targets exist both inside and outside the pain pathways. MrgprX1, a human GPCR, is a promising target of novel pain inhibitors, mainly because of its restricted expression in pain-sensing neurons. Many pharmaceutical companies have conducted drug screens to target human MrgprX1. However, constrained by species differences across Mrgprs, many drug candidates activate MrgprX1 but not the rodent orthologues, leaving no animal model responsive to test the effect on pain in vivo. To overcome the species specificity problem, Xinzhong Dong's lab generated a transgenic mouse line in which they replaced mouse Mrgprs with human MrgprX1. This valuable humanized mouse allowed them to characterize a potent positive allosteric modulator of MrgprX1, ML382. Cellular studies in humanized MrgprX1 mice suggest that ML382 enhances the ability of MrgprX1 to inhibit N-type Ca2+ channels via the Gi pathway in nociceptive neurons and block presynaptic terminal transmission in spinal cord. Importantly, ML382 effectively attenuates evoked persistent and spontaneous pain without causing peripheral or central side effects such as itch, motor dysfunction, or reward in the naïve condition. The group's findings suggest that humanized MrgprX1 mice provide an essential preclinical model and that activating MRGPRX1 is an effective way to treat persistent pain.
Kai Liu, a Neuroscience Gradaute student in Dr. Seth Blackshaw's lab, has been awarded the Mette Srand Research Award. He will give a talk and receive his award as part of the Young Investigator's Day Program on May 9th, 2017 from 3-5pm in Mountcastle Auditorium. This marks the 40th anniversary of the JHMI Young Investigator's Day which highlights talented graduate student and postdoctoral scientists.
The full Young Investigator's Day program will be released soon. You can view the 2016 Young Investigator winners here.
The hippocampus is a brain area involved in learning and memory. The dentate gyrus, a subregion of the hippocampus, may prevent interference between similar memories, but it is unclear how the two main dentate gyrus cell types, granule cells and mossy cells, contribute to this process. GoodSmith et al. recorded from granule cells and mossy cells as rats explored distinct environments. Different groups of granule cells fired in different environments, but mossy cells fired in multiple locations in most environments, a feature previously attributed to granule cells. This study resolves a longstanding debate about the firing properties of granule cells, shows that mossy cells have spatial firing, and describes distinct ways in which granule cells and mossy cells can contribute to the ability to distinguish between environments.
Sleep is an essential process that plays a critical role in supporting cognitive functions such as learning and memory consolidation. Synapses in the brain are the structures responsible for forming and maintaining memories. Studying mice, we found that synapses become stronger while the mice were awake and weaker during sleep by removal of the neurotransmitter receptors called AMPA receptors. This is a process called homeostatic scaling-down. Scaling-down during sleep was driven by a protein called Homer1a which builds up in neurons while the mice were awake but is prevented from accessing the synapses until sleep, by the arousal promoting neuromodulator noradrenaline. In this way, the scaling of synapses is limited while awake and engaged as we transition to sleep. Homer1a targeting to synapses was also observed during sleep deprivation, activated by the sleep promoting neuromodulator adenosine. Sleep is well known to enhance memory consolidation whereas sleep deprivation greatly impairs memory formation. Our study suggests that weakening of synapses during sleep contributes to learning and memory, and that if this process is engaged during sleep deprivation memories become lost.
Ph.D. candidate in neuroscience
Johns Hopkins University School of Medicine
Like many great ideas, Project Bridge emerged from confusion. Daniel Pham, a Ph.D. candidate in neuroscience, was unsuccessful in his attempt to describe to his partner the intricacies of his research. The communication breakdown led Pham and colleagues to found Project Bridge, “with the goal of getting scientists to communicate and connect with the public,” he says. The outreach program features talks and demonstrations by Johns Hopkins scientists in farmers markets, cafes and restaurants. In September, Project Bridge brought Baltimore Brain Fest, a daylong neuroscience expo, to a city elementary school. “It’s a very grass-roots approach, getting bystanders to come by and having scientists in the community, explaining rudimentary topics,” Pham says.
Publications from Primary Faculty Members - February 2017:
Agarwal A, Wu PH, Hughes EG, Fukaya M, Tischfield MA, Langseth AJ, Wirtz D, Bergles DE. Transient Opening of the Mitochondrial Permeability Transition Pore Induces Microdomain Calcium Transients in Astrocyte Processes. Neuron. 2017 Feb 8;93(3):587-605.e7. doi: 10.1016/j.neuron.2016.12.034. Epub 2017 Jan 26.
Diering GH, Nirujogi RS, Roth RH, Worley PF, Pandey A, Huganir RL. Homer1a drives homeostatic scaling-down of excitatory synapses during sleep. Science. 2017 Feb 3;355(6324):511-515. doi: 10.1126/science.aai8355. Epub 2017 Feb 2.
Fu C, Xu J, Cheng W, Rojas T, Chin AC, Snowman AM, Harraz MM, Snyder SH. Neuronal migration is mediated by inositol hexakisphosphate kinase 1 via α-actinin and focal adhesion kinase. Proc Natl Acad Sci U S A. 2017 Feb 2. pii: 201700165. doi: 10.1073/pnas.1700165114. [Epub ahead of print]
GoodSmith D, Chen X, Wang C, Kim SH, Song H, Burgalossi A, Christian KM, Knierim JJ. Spatial Representations of Granule Cells and Mossy Cells of the Dentate Gyrus. Neuron. 2017 Feb 8;93(3):677-690.e5. doi: 10.1016/j.neuron.2016.12.026. Epub 2017 Jan 26.
Smith-Hicks CL, Cai P, Savonenko AV, Reeves RH, Worley PF. Increased Sparsity of Hippocampal CA1 Neuronal Ensembles in a Mouse Model of Down Syndrome. Front Neural Circuits. 2017 Feb 3;11:6. doi: 10.3389/fncir.2017.00006. eCollection 2017.
Yue WW, Frederiksen R, Ren X, Luo DG, Yamashita T, Shichida Y, Cornwall MC, Yau KW. Spontaneous activation of visual pigments in relation to openness/closedness of chromophore-binding pocket. Elife. 2017 Feb 10;6. pii: e18492. doi: 10.7554/eLife.18492.
This Society for Neuroscience podcast takes the listener through the process of publishing a paper, starting from the initial conceptions of the experiment through to the final publication. Viewpoints from both the authors of the paper and journal editors are explored. In episode 2, starting at ~10:00, Jim Knierim, a former Reviewing Editor of The Journal of Neuroscience, discusses the sometimes tricky balance between trying to “sell” your work in order to make it appealing to a broad audience while not also over-selling the work by overinterpreting the results or making promises in the introduction that are ultimately not delivered in the results. He also emphasizes the importance of careful preparation of a manuscript before submission.
Listen to the Peril of Publishing Podcast episode on Neuroonline
Language, music, art, religious worship, self-awareness, planning, problem-solving, making tools. No other animal has all of these aptitudes. All rely on a single organ: the brain. But the brain is the most poorly understood organ of the human body. Seeking to change that, a $20 million partnership between the Kavli Foundation and The Johns Hopkins University was formed on Oct. 1, 2015. The Kavli Neuroscience Discovery Institute (Kavli NDI), led by neuroscientist Richard Huganir and computational scientist Michael Miller, is an interdisciplinary group of Johns Hopkins scientists who will harness the problem-solving aptitudes of their brains to devise tools that unlock the mysteries of neuroscience.
Daniel O’Connor was among 102 scientists and engineers named on Jan. 9 by President Obama as recipients of the Presidential Early Career Award for Scientists and Engineers, the highest honor bestowed by the United States Government on science and engineering professionals in the early stages of their independent research careers.
A clump of just a few thousand brain cells, no bigger than a mustard seed, controls the daily ebb and flow of most bodily processes in mammals -- sleep/wake cycles, most notably. Now, Johns Hopkins scientists report direct evidence in mice for how those cell clusters control sleep and relay light cues about night and day throughout the body.
Publications from Primary Faculty Members - January 2017:
Cave C, Park S, Rodriguez M, Nakamura M, Hoke A, Pletnikov M, Sockanathan S. GDE2 is essential for neuronal survival in the postnatal mammalian spinal cord. Mol Neurodegener. 2017 Jan 19;12(1):8. doi: 10.1186/s13024-017-0148-1.
Publications from Primary Faculty Members - December 2016:
Bedont JL, LeGates TA, Buhr E, Bathini A, Ling JP, Bell B, Wu MN, Wong PC, Van Gelder RN, Mongrain V, Hattar S, Blackshaw S. An LHX1-Regulated Transcriptional Network Controls Sleep/Wake Coupling and Thermal Resistance of the Central Circadian Clockworks. Curr Biol. 2017 Jan 9;27(1):128-136. doi: 10.1016/j.cub.2016.11.008. Epub 2016 Dec 22.