A striking feature of the mature central nervous system is the precision of its synaptic circuitry. More than 80 billion neurons in the human brain are precisely connected to one another through trillions of synapses. Much of the wiring is established in the absence of neural activity or experience indicating the basic organization of neural pathways is encoded in the genetic program. Recent studies support that several devastating developmental diseases, including autism and schizophrenia, have as their root cause modifications in the genetic program that ultimately disrupt the balance of synaptic connections. In order to understand how synapse specificity is achieved and how it is altered in human diseases, we investigate mechanisms controlling pathway development and synaptogenesis in development and how these same mechanisms influence synapse stability and plasticity in adulthood.
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, in press.
Hsiao K, Harony-Nicolas H, Buxbaum JD, +Bozdagi-Gunal O, +Benson DL. (2016) Cyfip1 regulates presynaptic activity during development. J. Neuroscience 36:1564-76.
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 cortico-striatal circuits. Journal of Comparative Neurology, 523:75-92. PMID 25158904
Friedman LG, Benson DL, Huntley GW. (2015) Cadherin-based transsynaptic networks in establishing and modifying neural connectivity. Current Topics in Devopmental Biology:112:415-65.
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. Role for NUP62 depletion and PYK2 redistribution in dendritic retraction resulting from chronic stress. (2014) 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. Hippocampus. (2014) N-cadherin regulates molecular organization of excitatory and inhibitory synaptic circuits in adult hippocampus in vivo. Aug;24(8):943-62
Fargali S, Garcia AL, Sadahiro M, Jiang C, Janssen WG, Lin WJ, Cogliani V, Elste A, Mortillo S, Cero C, Veitenheimer B, Graiani G, Pasinetti GM, Mahata SK, Osborn JW, Huntley GW, Phillips GR, Benson DL, Bartolomucci A, Salton SR. (2014) The granin VGF promotes genesis of secretory vesicles, and regulates circulating catecholamine levels and blood pressure. FASEB J. May;28(5):2120-33
Hsiao K, Bozdagi O, Benson DL. (2014) Axonal cap-dependent translation regulates presynaptic p35. Dev Neurobiol. Mar;74 (3):351-64.
Hsiao K, Bozdagi O, Benson DL. (2014) Axonal cap-dependent translation regulates presynaptic p35. Dev Neurobiol. Mar;74 (3):351-64. Mintz CD, Barrett KMS, Benson DL, Harrison NL. Anesthetics interfere with axon guidance in developing mouse neocortical neurons via a GABAA receptor mechanism. Anesthesiology, 118: 825-833, 2013.
Sepulveda B, Mesias R, Li X, Yue Z, Benson DL, Short- and long-term effects of LRRK2 on axon and dendrite growth, PLoS One 8: e61986, 2013.
Davies P, Hinkle KM, Sukar N, Sepulveda B, Mesias R, Serrano G, Alessi D, Beach TG, Benson DL, White CL, Cowell R, Das SS, West AB, Melrose HL. A comprehensive evaluation of Leucine Rich Repeat Kinase 2 monoclonal antibodies in rodent and human brain, Biochemical Journal 453: 101-13, 2013.
Hsiao K, Bozdagi O, Benson DL. (2014) Axonal cap-dependent translation regulates presynaptic p35. Dev Neurobiol. Mar;74 (3):351-64. Mortillo S, Elste AM, Ge Y., Patil SB, Hsiao K, Huntley GW, Davis RL, Benson DL. Compensatory redistribution of neuroligins and N-cadherin following deletion of synaptic ß1-integrin. Journal of Comparative Neurology, 520: 2041-52, 2012.
Benson DL and Huntley GW. Synapse adhesion: a dynamic equilibrium conferring stability and flexibility, Current Opinion in Neurobiology, 22: 397-404, 2012.
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