As the human brain develops, millions of neurons form trillions of synapses with a precision that is absolutely essential, but poorly understood. The onset and offset of gene sequences and programs serve to establish a baseline organization that activity and experience sculpt into a working unit capable of responding appropriately to external stimuli and able to generate novel ideas and poetry. Mutations in any of a variety of genes can modify the process in ways that can give rise to developmental disorders like autism or schizophrenia or set the stage for degenerative disorders like Huntington’s or Parkinson’s Disease. To better understand normal brain development and its vulnerability to disorders we have been studying the generation and function of synapses in mice carrying gene mutations that in humans are known to give rise to developmental or neurodegenerative diseases.
Benson DL (2020) Of molecules and mechanisms. J Neurosci 40:81-88. doi: 10.1523/JNEUROSCI.0743-19.2019
Benson DL and Huntley GW (2019) Are we listening to everything the PARK genes are telling us? J Comp Neurol 527: 1527-1540. doi: 10.1002/cne.24642
Benson DL, Matikainen-Ankney BA, Hussein A, Huntley GW (2018) Functional and behavioral consequences of Parkinson’s disease-associated LRRK2-G2019S mutation. Biochemical Society Transactions 38:9700-9711. doi: 10.1042/BST20180468.
Matikainen-Ankney BA*, Kezunovic N*, Menard C1, Flanigan M, Zhong Y, Russo SJ, Benson DL§ and Huntley GW§ (2018) Parkinson’s disease-linked leucine-rich repeat kinase 2-G2019S mutation alters synaptic plasticity and promotes resilience to chronic social stress in young adulthood. J Neurosci. 38:9700-9711. doi: 10.1523/JNEUROSCI.1457-18.2018.
Bardot E, Tzavaras N, Benson DL, Dubois NC (2017) Quantitative whole-mount immunofluorescence analysis of cardiac progenitor populations in mouse embryos. J Vis Exp. 2017 Oct 12;(128). doi: 10.3791/56446.
Matikainen-Ankney BA*, Kezunovic N*, Mesias RE, Tian Y, Williams FM, +Huntley GW, +Benson DL (2016) Altered development of synapse structure and function in striatum caused by Parkinson’s disease-linked LRRK2-G2019S mutation. Journal of Neuroscience, J Neuroscience, 27:7128-41.doi: 10.1523/JNEUROSCI.3314-15.2016.
Hsiao K, Harony-Nicolas H, Buxbaum JD, +Bozdagi-Gunal O, +Benson DL (2016) Cyfip1 regulates presynaptic activity during development. J. Neuroscience 36:1564-76. doi: 10.1523/JNEUROSCI.0511-15.2016.
Carcea I, Benson DL (2016) Visualizing and characterizing Semaphorin endocytic events using quantum dot conjugated proteins. Methods in Molecular Biology, in “Semaphorin Signaling: Methods and Protocols. Vol 1493. Editor Jonathan R Terman.
Friedman LG, Riemslagh FW, Sullivan JM, Mesias R, Williams FM, Huntley GW, Benson DL (2015) Cadherin-8 expression, synaptic localization and molecular control of neuronal form in prefrontal corticostriatal circuits. Journal of Comparative Neurology, 523:75-92. PMID 25158904. doi: 10.1002/cne.23666. Epub 2014 Sep 22.
Friedman LG, Benson DL, Huntley GW (2015) Cadherin-based transsynaptic networks in establishing and modifying neural connectivity. Current Topics in Developmental Biology:112:415-65. doi: 10.1016/bs.ctdb.2014.11.025.
Hsiao K, Bozdagi O, Benson DL (2014) Axonal cap-dependent translation regulates presynaptic p35. Dev Neurobiol. Mar;74 (3):351-64.
Carcea I, Patil SB, Robison AJ, Mesias R, Huntsman MM, Froemke RC, Buxbaum JD, Huntley GW, Benson DL (2014) Maturation of cortical circuits requires Sema7A. Proc Natl Acad Sci, USA 111: 13978-83.
Kinoshita Y, Hunter RG, Gray JD, Mesias R, McEwen BS, Benson DL, Kohtz DS (2014) Role for NUP62 depletion and PYK2 redistribution in dendritic retraction resulting from chronic stress. Proc Natl Acad Sci U S A. 2014 Nov 11;111(45):16130-5
Nikitczuk JS, Patil SB, Matikainen-Ankney BA, Scarpa J, Shapiro ML, Benson DL, Huntley GW (2014) N-cadherin regulates molecular organization of excitatory and inhibitory synaptic circuits in adult hippocampus in vivo. Hippocampus Aug;24(8):943-62
Mintz CD, Barrett KMS, Benson DL, Harrison NL (2013) Anesthetics interfere with axon guidance in developing mouse neocortical neurons via a GABAA receptor mechanism. Anesthesiology, 118: 825-833.
Sepulveda B, Mesias R, Li X, Yue Z, Benson DL (2013) Short- and long-term effects of LRRK2 on axon and dendrite growth, PLoS One 8: e61986.
Mortillo S, Elste AM, Ge Y., Patil SB, Hsiao K, Huntley GW, Davis RL, Benson DL (2012) Compensatory redistribution of neuroligins and N-cadherin following deletion of synaptic ß1-integrin. Journal of Comparative Neurology, 520: 2041-52.
Benson DL and Huntley GW (2012) Synapse adhesion: a dynamic equilibrium conferring stability and flexibility, Current Opinion in Neurobiology, 22: 397-404.
Huntley GW, Elste AM, Patil SB, Bozdagi O, Benson DL, and Steward O (2012) Synaptic loss and retention of different classic cadherins with LTP-associated synaptic structural remodeling in vivo. Hippocampus 22, 17 – 28.
Benson DL and Huntley, GW (2012) Building and remodeling synapses. Hippocampus, 22: 954-968.
Sepulveda B, Carcea I, Zhao B, Salton SRJ, Benson DL (2011) L1CAM promotes resistance to alcohol-induced silencing of growth cone responses to guidance cues, Neuroscience 180: 30-40.
Carcea I, Ma’ayan A, Mesias R, Sepulveda B, Salton SR, Benson DL (2010) Flotillin-mediated endocytic events dictate cell-type specific responses to Semaphorin 3A, Journal of Neuroscience 30:15317-15329.
*Bozdagi O, *Wang X, *Nikitczuk JS, Anderson TR, Bloss EG, Radice GL, Zhou Q, +Benson DL, +Huntley GW (2010) Persistence of coordinated LTP and dendritic spine enlargement at mature synapses requires N-cadherin, Journal of Neuroscience, 30:9984-9989. Highlighted in J Neuroscience
Meet the Team
Current Position: NIH
Current Position: Amgen