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
The lab of Professor of Neuroscience James Knierim in the Zanvyl Krieger Mind/Brain Institute published a paper in Science that discovered a new role of the Lateral Entorhinal Cortex (LEC)—one of the gateways of information into the hippocampal memory system. The paper’s lead authors, Cheng Wang and Xiaojing Chen, showed that the LEC encodes experience from a first-person (egocentric) perspective, in contrast to the world-centered (allocentric) coding of place cells, grid cells, and head direction cells. This discovery supports the idea that the LEC conveys information about the sensory content of an organisms’ experience, which the hippocampus binds within the allocentric maps provided by grid cells and place cells to form the basis of an episodic memory of an event within its spatiotemporal context.
Link to article: http://science.sciencemag.org/content/362/6417/945.long
Publications for Primary Faculty Members - October 2018:
Jiang Z, Yue WWS, Chen L, Sheng Y, Yau KW. Cyclic-Nucleotide- and HCN-Channel-Mediated Phototransduction in Intrinsically Photosensitive Retinal Ganglion Cells. Cell. 2018 Oct 18;175(3):652-664.e12. doi: 10.1016/j.cell.2018.08.055.
Ottenheimer D, Richard JM, Janak PH. Ventral pallidum encodes relative reward value earlier and more robustly than nucleus accumbens. Nat Commun. 2018 Oct 19;9(1):4350. doi: 10.1038/s41467-018-06849-z.
Working with rats, researchers have found robust neural activity related to food choice in a previously overlooked part of the brain. The findings, published in the journal Nature Communications, suggest this brain area could be key to developing therapies and treatments to encourage healthy eating.
Publications for Primary Faculty Members - September 2018:
Leech KA, Day KA, Roemmich RT, Bastian AJ. Movement and perception recalibrate differently across multiple days of locomotor learning. J Neurophysiol. 2018 Sep 5. doi: 10.1152/jn.00355.2018. [Epub ahead of print]
Rodríguez G, Chakraborty D, Schrode KM, Saha R, Uribe I, Lauer AM, Lee HK. Cross-Modal Reinstatement of Thalamocortical Plasticity Accelerates Ocular Dominance Plasticity in Adult Mice. Cell Rep. 2018 Sep 25;24(13):3433-3440.e4. doi: 10.1016/j.celrep.2018.08.072.
GAMBLING MONKEYS LIKE BIG BETS, STUDY FINDS
Scientists locate area of brain linked to high-risk behavior, a possible step toward improved treatments for destructively risky behaviors in humans
Monkeys who learned how to gamble have helped researchers pinpoint an area of the brain key to one's willingness to make risky decisions.
By studying the genome of a kind of octopus not known for its friendliness toward its peers, then testing its behavioral reaction to a popular mood-altering drug called MDMA or “ecstasy,” scientists say they have found preliminary evidence of an evolutionary link between the social behaviors of the sea creature and humans, species separated by 500 million years on the evolutionary tree.
A summary of the experiments is published Sept. 20 in Current Biology, and if the findings are validated, the researchers say, they may open opportunities for accurately studying the impact of psychiatric drug therapies in many animals distantly related to people.
Publications for Primary Faculty Members - August 2018:
Babola TA, Li S, Gribizis A, Lee BJ, Issa JB, Wang HC, Crair MC, Bergles DE. Homeostatic Control of Spontaneous Activity in the Developing Auditory System. Neuron. 2018 Aug 8;99(3):511-524.e5. doi: 10.1016/j.neuron.2018.07.004. Epub 2018 Aug 1.
Cherry-Allen KM, Statton MA, Celnik PA, Bastian AJ.A Dual-Learning Paradigm Simultaneously Improves Multiple Features of Gait Post-Stroke. Neurorehabil Neural Repair. 2018 Aug 7:1545968318792623. doi: 10.1177/1545968318792623. [Epub ahead of print]
Chin SG, Maguire SE, Huoviala P, Jefferis GSXE, Potter CJ. Olfactory Neurons and Brain Centers Directing Oviposition Decisions in Drosophila. Cell Rep. 2018 Aug 7;24(6):1667-1678. doi: 10.1016/j.celrep.2018.07.018.
Lilley BN, Sabbah S, Hunyara JL, Gribble KD, Al-Khindi T, Xiong J, Wu Z, Berson DM, Kolodkin AL. Genetic access to neurons in the accessory optic system reveals a role for Sema6A in midbrain circuitry mediating motion perception. J Comp Neurol. 2018 Aug 3. doi: 10.1002/cne.24507. [Epub ahead of print]
Newman EA, Wu D, Taketo MM, Zhang J, Blackshaw S. Canonical Wnt signaling regulates patterning, differentiation and nucleogenesis in mouse hypothalamus and prethalamus. Dev Biol. 2018 Jul 29. pii: S0012-1606(18)30451-2. doi: 10.1016/j.ydbio.2018.07.021. [Epub ahead of print]
Saunders BT, Richard JM, Margolis EB, Janak PH. Dopamine neurons create Pavlovian conditioned stimuli with circuit-defined motivational properties. Nat Neurosci. 2018 Aug;21(8):1072-1083. doi: 10.1038/s41593-018-0191-4. Epub 2018 Jul 23.
Sun S, Babola T, Pregernig G, So KS, Nguyen M, Su SM, Palermo AT, Bergles DE, Burns JC, Müller U. Hair Cell Mechanotransduction Regulates Spontaneous Activity and Spiral Ganglion Subtype Specification in the Auditory System. Cell. 2018 Jul 30. pii: S0092-8674(18)30902-4. doi: 10.1016/j.cell.2018.07.008. [Epub ahead of print]
Therrien AS, Wolpert DM, Bastian AJ. Increasing Motor Noise Impairs Reinforcement Learning in Healthy Individuals. eNeuro. 2018 Aug 13;5(3). pii: ENEURO.0050-18.2018. doi: 10.1523/ENEURO.0050-18.2018. eCollection 2018 May-Jun.
Publications from Primary Faculty Members - May 2018:
Bridi MCD, de Pasquale R, Lantz CL, Gu Y, Borrell A, Choi SY, He K, Tran T, Hong SZ, Dykman A, Lee HK, Quinlan EM, Kirkwood A. Two distinct mechanisms for experience-dependent homeostasis. Nat Neurosci. 2018 May 14. doi: 10.1038/s41593-018-0150-0. [Epub ahead of print]
Fu C, Rojas T, Chin AC, Cheng W, Bernstein IA, Albacarys LK, Wright WW, Snyder SH. Multiple aspects of male germ cell development and interactions with Sertoli cells require inositol hexakisphosphate kinase-1. Sci Rep. 2018 May 4;8(1):7039. doi: 10.1038/s41598-018-25468-8.
Li RC, Lin CC, Ren X, Wu JS, Molday LL, Molday RS, Yau KW. Ca2+-activated Cl current predominates in threshold response of mouse olfactory receptor neurons. Proc Natl Acad Sci U S A. 2018 May 7. pii: 201803443. doi: 10.1073/pnas.1803443115. [Epub ahead of print]
Minamisawa G, Kwon SE, Chevée M, Brown SP, O'Connor DH. A Non-canonical Feedback Circuit for Rapid Interactions between Somatosensory Cortices. Cell Rep. 2018 May 29;23(9):2718-2731.e6. doi: 10.1016/j.celrep.2018.04.115.
Publications from Primary Faculty Members - April 2018:
de Melo J, Clark BS, Venkataraman A, Shiau F, Zibetti C, Blackshaw S. Ldb1 and Rnf12-dependent regulation of Lhx2 controls the relative balance between neurogenesis and gliogenesis in retina. Development. 2018 Apr 12. pii: dev.159970. doi: 10.1242/dev.159970. [Epub ahead of print]
Heo S, Diering GH, Na CH, Nirujogi RS, Bachman JL, Pandey A, Huganir RL. Identification of long-lived synaptic proteins by proteomic analysis of synaptosome protein turnover. Proc Natl Acad Sci U S A. 2018 Apr 17;115(16):E3827-E3836. doi: 10.1073/pnas.1720956115. Epub 2018 Apr 2.
Newman EA, Kim DW, Wan J, Wang J, Qian J, Blackshaw S. Foxd1 is required for terminal differentiation of anterior hypothalamic neuronal subtypes. Dev Biol. 2018 Apr 18. pii: S0012-1606(17)30906-5. doi: 10.1016/j.ydbio.2018.04.012. [Epub ahead of print]
Weyemi U, Paul BD, Snowman AM, Jailwala P, Nussenzweig A, Bonner WM, Snyder SH. Histone H2AX deficiency causes neurobehavioral deficits and impaired redox homeostasis. Nat Commun. 2018 Apr 18;9(1):1526. doi: 10.1038/s41467-018-03948-9.
Xie T, Ho MC, Liu Q, Horiuchi W, Lin CC, Task D, Luan H, White BH, Potter CJ, Wu MN. A Genetic Toolkit for Dissecting Dopamine Circuit Function in Drosophila. Cell Rep. 2018 Apr 10;23(2):652-665. doi: 10.1016/j.celrep.2018.03.068.
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 - March 2018:
Day KA, Leech KA, Roemmich RT, Bastian AJ. Accelerating locomotor savings in learning: compressing four training days to one. J Neurophysiol. 2018 Mar 14. doi: 10.1152/jn.00903.2017. [Epub ahead of print]
Hughes EG, Orthmann-Murphy JL, Langseth AJ, Bergles DE. Myelin remodeling through experience-dependent oligodendrogenesis in the adult somatosensory cortex. Nat Neurosci. 2018 Mar 19. doi: 10.1038/s41593-018-0121-5. [Epub ahead of print]
Kornberg MD, Bhargava P, Kim PM, Putluri V, Snowman AM, Putluri N, Calabresi PA, Snyder SH. Dimethyl fumarate targets GAPDH and aerobic glycolysis to modulate immunity. Science. 2018 Mar 29. pii: eaan4665. doi: 10.1126/science.aan4665. [Epub ahead of print]
Larson VA, Mironova Y, Vanderpool KG, Waisman A, Rash JE, Agarwal A, Bergles DE. Oligodendrocytes control potassium accumulation in white matter and seizure susceptibility. Oligodendrocytes control potassium accumulation in white matter and seizure susceptibility. Elife. 2018 Mar 29;7. pii: e34829. doi: 10.7554/eLife.34829.
Richard JM, Stout N, Acs D, Janak PH. Ventral pallidal encoding of reward-seeking behavior depends on the underlying associative structure. Elife. 2018 Mar 22;7. pii: e33107. doi: 10.7554/eLife.33107.
Sbodio JI, Snyder SH, Paul BD. REDOX MECHANISMS IN NEURODEGENERATION: FROM DISEASE OUTCOMES TO THERAPEUTIC OPPORTUNITIES. Antioxid Redox Signal. 2018 Mar 21. doi: 10.1089/ars.2017.7321. [Epub ahead of print]
Venkataraman A, Yang K, Irizarry J, Mackiewicz M, Mita P, Kuang Z, Xue L, Ghosh D, Liu S, Ramos P, Hu S, Bayron Kain D, Keegan S, Saul R, Colantonio S, Zhang H, Behn FP, Song G, Albino E, Asencio L, Ramos L, Lugo L, Morell G, Rivera J, Ruiz K, Almodovar R, Nazario L, Murphy K, Vargas I, Rivera-Pacheco ZA, Rosa C, Vargas M, McDade J, Clark BS, Yoo S, Khambadkone SG, de Melo J, Stevanovic M, Jiang L, Li Y, Yap WY, Jones B, Tandon A, Campbell E, Montelione GT, Anderson S, Myers RM, Boeke JD, Fenyö D, Whiteley G, Bader JS, Pino I, Eichinger DJ, Zhu H, Blackshaw S. A toolbox of immunoprecipitation-grade monoclonal antibodies to human transcription factors. Nat Methods. 2018 Mar 19. doi: 10.1038/nmeth.4632. [Epub ahead of print]
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