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
Richard Huganir and colleagues report success in using large-scale studies of proteins and high-tech chemical analysis to discover 164 proteins within synapses in mice that outlast neighboring proteins by weeks and months. These stable proteins, they say, may be part of the molecular machinery that governs long-term memory and learning—as well as loss of memory—in all mammals, including humans. A summary of their experiments is published the week of April 2 in the Proceedings of the National Academy of Sciences.
Paper link: https://doi.org/10.1073/pnas.1720956115
Publications from Primary Faculty Members - February 2018:
Han L, Limjunyawong N, Ru F, Li Z, Hall OJ, Steele H, Zhu Y, Wilson J, Mitzner W, Kollarik M, Undem BJ, Canning BJ, Dong X. Mrgprs on vagal sensory neurons contribute to bronchoconstriction and airway hyper-responsiveness. Nat Neurosci. 2018 Feb 5. doi: 10.1038/s41593-018-0074-8. [Epub ahead of print]
Sasikumar D, Emeric E, Stuphorn V, Connor CE. First-Pass Processing of Value Cues in the Ventral Visual Pathway. Curr Biol. 2018 Feb 19;28(4):538-548.e3. doi: 10.1016/j.cub.2018.01.051. Epub 2018 Feb 8.
Publications from Primary Faculty Members - January 2018:
Chevée M, Robertson JJ, Cannon GH, Brown SP, Goff LA. Variation in Activity State, Axonal Projection, and Position Define the Transcriptional Identity of Individual Neocortical Projection Neurons. Cell Rep. 2018 Jan 9;22(2):441-455. doi: 10.1016/j.celrep.2017.12.046.
Publications from Primary Faculty Members - December 2017:
Fischbach-Weiss, S, Reese, RM, Janak, PH. Inhibiting Mesolimbic Dopamine Neurons Reduces the Initiation and Maintenance of Instrumental Responding. Neuroscience. 2017 Dec 15. pii: S0306-4522(17)30874-6. doi: 10.1016/j.neuroscience.2017.12.003. [Epub ahead of print]
Fu C, Tyagi R, Chin AC, Rojas T, Li RJ, Guha P, Bernstein IA, Rao F, Xu R, Cha JY, Xu J, Snowman AM, Semenza GL, Snyder SH. Inositol Polyphosphate Multikinase Inhibits Angiogenesis via Inositol Pentakisphosphate-Induced HIF-1α Degradation. Circ Res. 2017 Dec 26. pii: CIRCRESAHA.117.311983. doi: 10.1161/CIRCRESAHA.117.311983. [Epub ahead of print]
Paul, BD, Snyder, SH. Gasotransmitter Hydrogen Sulfide Signaling in Neuronal Health and Disease. Biochem Pharmacol. 2017 Dec 1. pii: S0006-2952(17)30700-1. doi: 10.1016/j.bcp.2017.11.019. [Epub ahead of print]
Piard J, Hu JH, Campeau PM, Rzonca S, Van Esch H, Vincent E, Han M, Rossignol E, Castaneda J, Chelly J, Skinner C, Kalscheuer VM10, Wang R, Lemyre E, Kosinska J, Stawinski P, Bal J, Hoffman DA, Schwartz CE, Van Maldergem L, Wang T, Worley P. FRMPD4 Mutations Cause X-linked Intellectual Disability and Disrupt Dendritic Spine Morphogenesis. Hum Mol Genet. 2017 Dec 18. doi: 10.1093/hmg/ddx426. [Epub ahead of print]
Scherer, PC, Zaccor, NW, Neumann, NM, Vasavda, C, Barrow, R, Ewald, AJ, Rao, F, Sumner, CJ, Snyder, SH. TRPV1 is a physiological regulator of μ-opioid receptors. Proc Natl Acad Sci U S A. 2017 Dec 4. pii: 201717005. doi: 10.1073/pnas.1717005114. [Epub ahead of print]
Publications from Primary Faculty Members - November 2017:
Hu, B, Niebur, E. A recurrent neural model for proto-object based contour integration and figure-ground segregation. J Comput Neurosci. 2017 Dec;43(3):227-242. doi: 10.1007/s10827-017-0659-3. Epub 2017 Sep 19.
Wang Q, Chiu SL, Koropouli E, Hong I, Mitchell S, Easwaran TP, Hamilton NR, Gustina AS, Zhu Q, Ginty DD, Huganir RL, Kolodkin AL. Neuropilin-2/PlexinA3 Receptors Associate with GluA1 and Mediate Sema3F-Dependent Homeostatic Scaling in Cortical Neurons. Neuron. 2017 Nov 14. pii: S0896-6273(17)31021-8. doi: 10.1016/j.neuron.2017.10.029. [Epub ahead of print]
Publications from Primary Faculty Members - October 2017:
Publications from Primary Faculty Members - September 2017:
Vandaele Y, Pribut HJ, Janak PH. Lever Insertion as a Salient Stimulus Promoting Insensitivity to Outcome Devaluation. Front Integr Neurosci. 2017 Sep 27;11:23. doi: 10.3389/fnint.2017.00023. eCollection 2017.
Johns Hopkins researchers report the unexpected presence of a type of neuron in the brains of mice that appears to play a central role in promoting sleep by turning ‘off’ wake-promoting neurons. The newly identified brain cells, located in a part of the hypothalamus called the zona incerta, they say, could offer novel drug targets to treat sleep disorders, such as insomnia and narcolepsy, caused by the dysfunction of sleep-regulating neurons.
Publications from Primary Faculty Members - July 2017:
Fraser KM, Janak PH. Long-lasting contribution of dopamine in the nucleus accumbens core, but not dorsal lateral striatum, to sign-tracking. Eur J Neurosci. 2017 Jul 12. doi: 10.1111/ejn.13642. [Epub ahead of print]
Langseth AJ, Kim J, Ugolino JE, Shah Y, Hwang HY, Wang J, Bergles DE, Brown SP. Cell-type specific differences in promoter activity of the ALS-linked C9orf72 mouse ortholog. Sci Rep. 2017 Jul 18;7(1):5685. doi: 10.1038/s41598-017-05864-2.
Publications from Primary Faculty Members - June 2017:
Harraz MM, Snyder SH. Antidepressant Actions of Ketamine Mediated by the Mechanistic Target of Rapamycin, Nitric Oxide, and Rheb. Neurotherapeutics. 2017 Jun 13. doi: 10.1007/s13311-017-0540-0. [Epub ahead of print]
Jeck DM, Qin M, Egeth H, Niebur E. Attentive pointing in natural scenes correlates with other measures of attention. Vision Res. 2017 Jun;135:54-64. doi: 10.1016/j.visres.2017.04.001. Epub 2017 May 8.
Wang Q, Yue WWS, Jiang Z, Xue T, Kang SH, Bergles DE, Mikoshiba K, Offermanns S, Yau KW. Synergistic Signaling by Light and Acetylcholine in Mouse Iris Sphincter Muscle. Curr Biol. 2017 Jun 19;27(12):1791-1800.e5. doi: 10.1016/j.cub.2017.05.022. Epub 2017 Jun 1.
Xie X, Tabuchi M, Brown MP, Mitchell SP, Wu MN, Kolodkin AL. The laminar organization of the Drosophila ellipsoid body is semaphorin-dependent and prevents the formation of ectopic synaptic connections. Elife. 2017 Jun 20;6. pii: e25328. doi: 10.7554/eLife.25328. [Epub ahead of print]
In a report in the June 19 issue of the journal Current Biology, Neuroscience Professor King-Wai Yau and colleagues detail how the pupils in a mouse’s eyes get smaller when the animal is moved from a dark to a lit room even when the nerve connections between the animal’s brain and eyes are severed.
Publications from Primary Faculty Members - May 2017:
Cox E, Hwang W, Uzoma I, Hu J, Guzzo CM, Jeong J, Matunis MJ, 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 May;16(5):812-823. doi: 10.1074/mcp.M116.063719. Epub 2017 Mar 2.
Kajstura TJ, Dougherty SE, Linden DJ. Serotonin axons in the neocortex of the adult female mouse regrow after traumatic brain injury. J Neurosci Res. 2017 May 9. doi: 10.1002/jnr.24059. [Epub ahead of print]
Severson KS, Xu D, Van de Loo M, Bai L, Ginty DD, O'Connor DH. Active Touch and Self-Motion Encoding by Merkel Cell-Associated Afferents. Neuron. 2017 May 3;94(3):666-676.e9. doi: 10.1016/j.neuron.2017.03.045. Epub 2017 Apr 20.
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:
Grima JC, Daigle JG, Arbez N, Cunningham KC, Zhang K, Ochaba J, Geater C, Morozko E, Stocksdale J, Glatzer JC, Pham JT, Ahmed I, Peng Q, Wadhwa H, Pletnikova O, Troncoso JC, Duan W, Snyder SH, Ranum LP, Thompson LM, Lloyd TE, Ross CA, Rothstein JD. Mutant Huntingtin Disrupts the Nuclear Pore Complex. Neuron.2017 Apr 5;94(1):93-107.e6. doi: 10.1016/j.neuron.2017.03.023.
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.
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.
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.
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.
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.
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.
Publications from Primary Faculty Members - November 2016:
The Brain Uses Backward Instant Replays to Remember Important Travel Routes
'You Are Getting Sleepy,' Said The Scientist To The Fruit Fly