Synapse structure and function is continuously modified during development and throughout life by experience, such as learning new skills or forming new memories. Such synaptic plasticity is thus critical for normal brain function. Synaptic plasticity can also become maladaptive under conditions of brain, spinal or peripheral nerve injury, leading to abnormal function or sensation. Dr. Huntley’s research focuses on mechanisms of synaptic plasticity through which synaptic structure and function are modified by experience or injury. Research projects include: 1) the role of the cadherin family of synaptic adhesion proteins in synapse and circuit development, plasticity and repair; 2) the role of regulated extracellular proteolytic remodeling of cortical synapses in synaptic plasticity; and 3) molecules and mechanisms regulating aberrant corticostriatal circuit development and plasticity in autism and Parkinson’s disease models.
The synapse adhesion molecule neural (N)-cadherin is localized to developing thalamocortical synaptic junctional complexes. The larger image is a flattened, tangential section through layer IV of developing (P5) rat cortex which has been immunolabeled for N-cadherin. Terminal fields in the barrel (somatosensory) cortex (S1), auditory cortex (A1) and visual cortex (V1) are evident in the patterns of N-cadherin labeling. The confocal microscope images shown in the inset verify that such terminal fields are N-cadherin labeled thalamocortical synapses, shown in the overlay by the codistributions of FluoroRuby-labeled ventrobasal thalamic afferent terminals (red), immunolabeling for PSD-95 (blue)–which is concentrated in asymmetric postsynaptic densities–and N-cadherin (green). Modified from the article by G.W. Huntley and D.L. Benson, “N-Cadherin at developing thalamocortical synapses provides an adhesion mechanism for the formation of somatotopically organized connections.” Journal of Comparative Neurology 407:453-471 (1999).
It is tacitly understood that cell adhesion molecules (CAMs) are critically important for the development of cells, circuits, and synapses in the brain. What is less clear is what CAMs continue to contribute to brain structure and function after the early period of development.
Matikainen-Ankney BA, Kezunovic, N, Mesias RE, Tian Y, Williams GM, Huntley GW, Benson DL. Altered development of synapse structure and function in striatum caused by Parkinson’s disease-linked LRRK2-G2019S mutation. J Neurosci 2016 36:7128-7141.
Friedman LG, Benson Dl, Huntley GW. Cadherin-based trans-synaptic networks in establishing and modifying neural connectivity. Curr Top Dev Biol 2015 112:415-465.
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. J Comp Neurol 523:75-92.
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 2014 28:2120-2133.
Carcea I, Patil SB, Robison AJ, Mesias R, Huntsman MM, Froemke RC, Buxbaum JD, Huntley GW, Benson DL. (2014) Maturation of cortical circuits requires Sema 7A. Proc Natl Acad Sci USA 111:13978-13983.
Aujla P, Huntley GW. (2014) Early postnatal expression and localization of matrix metalloproteinases-2 and -9 during establishment of rat hippocampal synaptic circuitry. J Comp Neurol 522:1249-1263.
Nikitczuk, JS, Patil SB, Scarpa J, Shapiro ML, Benson DL, Huntley GW. (2014) N-cadherin regulates molecular organization of excitatory and inhibitory synpatic circuits in adult hippocampus in vivo. Hippocampus 24:943-962.
Arguello A, Ye X, Bozdagi O, Pollonini G, Tronel S., Bambah-Mukku D, Huntley, GW, Platano D, Alberini C. (2013) CCAAT enhancer binding protein delta plays an essential role in memory consolidation and reconsolidation. J. Neurosci 33:3646-3658.
Huntley, G.W. (2012) Synaptic circuit remodelling by matrix metalloproteinases in health and disease. Nat Rev Neurosci 2012 13:743-757.
Benson DL, Huntley GW. Building and remodeling synapses. Hippocampus 2012 22:954-968.
Huntley GW, Elste AM, Patil SB, Bozdagi O, Benson DL, Steward, O. Synaptic loss and retention of different classic cadherins with LTP-associated synaptic structural remodeling in vivo. Hippocampus 2012 22:17-28.
Mortillo, S., Elste, A., Ge, Y., Patil, S.B., Hsiao, K., Huntley, G.W. and Benson, D.L. (2012) Compensatory redistribution of neuroligins and N-cadherin following deletion of synaptic β 1-integrin. J. Comp. Neurol. 520:2041-2052.
Benson, D.L. and Huntley, G.W. (2012) Synapse adhesion: a dynamic equilibrium conferring stability and flexibility. Curr Opin Neurobiol 22:397-404.
Bozdagi, O., Wang, X., Martinelli, G.P., Prell, G., Friedrich, V.L., Huntley, G.W., and Holstein, G.R. (2011) Imidazoleacetic acid-ribotide induces depression of synaptic responses in hippocampus through activation of imidazonline receptors. J. Neurophysiol. 105:1266-1275.
Suzuki, A., Stern, S.A., Bozdagi, O., Huntley, G.W. Walker, R.H., Magistretti, P., and Alberini, C.M. (2011) The astrocyte-neuron lactate-shuttle is required for long-term memory. Cell 144:810-823.
Patil, S., Brock, J.H., Colman, D.R., and Huntley, G.W. (2011) GDNF-dependent modulation of cadherins in spinal dorsal horn in relationship to neuropathic pain. Pain 152:924-935.
Parikh, P., Hao, Y., Hosseinkhani, M., Patil, S.B., Huntley, G.W., Tessier-Lavigne, M., and Zou, H. (2011) Regeneration of axons in injured spinal cord by activation of BMP/Smad1 signaling pathway in adult neurons. Proc Natl Acad Sci USA 108:E99-E107.
Meet the Team
Nebojsa (Neso) Kezunovic
Neso is a postdoctoral fellow in George Huntley’s laboratory who is working with our lab on two projects focused on striatal circuit development.
Roxi is a graduate student in the Neuroscience program working on the synaptic adhesion protein cadherin-8 and it’s role in establishing corticostriatal circuit connectivity and function during early postnatal development. Roxi is also a Posse Foundation Alumna and an ative leader in the Posse community