Neuroligin-1 regulates excitatory synaptic transmission, LTP and EPSP-spike coupling in the dentate gyrus in vivo
Tóm tắt
Neuroligins are transmembrane cell adhesion proteins with a key role in the regulation of excitatory and inhibitory synapses. Based on previous in vitro and ex vivo studies, neuroligin-1 (NL1) has been suggested to play a selective role in the function of glutamatergic synapses. However, the role of NL1 has not yet been investigated in the brain of live animals. We studied the effects of NL1-deficiency on synaptic transmission in the hippocampal dentate gyrus using field potential recordings evoked by perforant path stimulation in urethane-anesthetized NL1 knockout (KO) mice. We report that in NL1 KOs the activation of glutamatergic perforant path granule cell inputs resulted in reduced synaptic responses. In addition, NL1 KOs displayed impairment in long-term potentiation. Furthermore, field EPSP-population spike (E-S) coupling was greater in NL1 KO than WT mice and paired-pulse inhibition was reduced, indicating a compensatory rise of excitability in NL1 KO granule cells. Consistent with changes in excitatory transmission, NL1 KOs showed a significant reduction in hippocampal synaptosomal expression levels of the AMPA receptor subunit GluA2 and NMDA receptor subunits GluN1, GluN2A and GluN2B. Taken together, we provide first evidence that NL1 is essential for normal excitatory transmission and long-term synaptic plasticity in the hippocampus of intact animals. Our data provide insights into synaptic and circuit mechanisms of neuropsychiatric abnormalities such as learning deficits and autism.
Tài liệu tham khảo
Abraham WC, Gustafsson B, Wigström H (1987) Long-term potentiation involves enhanced synaptic excitation relative to synaptic inhibition in guinea-pig hippocampus. J Physiol 394:367–380
Arons MH, Thynne CJ, Grabrucker AM, Li D, Schoen M, Cheyne JE, Boeckers TM, Montgomery JM, Garner CC (2012) Autism-associated mutations in ProSAP2/Shank3 impair synaptic transmission and neurexin-neuroligin-mediated transsynaptic signaling. J Neurosci 32:14966–14978
Blundell J, Blaiss CA, Etherton MR, Espinosa F, Tabuchi K, Walz C, Bolliger MF, Südhof TC, Powell CM (2010) Neuroligin-1 deletion results in impaired spatial memory and increased repetitive behavior. J Neurosci 30:2115–2129
Bourgeron T (2009) A synaptic trek to autism. Curr Opin Neurobiol 19:231–234
Bowden JB, Abraham WC, Harris KM (2012) Differential effects of strain, circadian cycle, and stimulation pattern on LTP and concurrent LTD in the dentate gyrus of freely moving rats. Hippocampus 22:1363–1370
Budreck EC, Kwon O-B, Jung JH, Baudouin S, Thommen A, Kim H-S, Fukazawa Y, Harada H, Tabuchi K, Shigemoto R et al (2013) Neuroligin-1 controls synaptic abundance of NMDA-type glutamate receptors through extracellular coupling. Proc Natl Acad Sci USA 110:725–730
Carlin RK, Grab DJ, Cohen RS, Siekevitz P (1980) Isolation and characterization of postsynaptic densities from various brain regions: enrichment of different types of postsynaptic densities. J Cell Biol 86:831–845
Chen SX, Tari PK, She K, Haas K (2010) Neurexin-neuroligin cell adhesion complexes contribute to synaptotropic dendritogenesis via growth stabilization mechanisms in vivo. Neuron 67:967–983
Chih B, Engelman H, Scheiffele P (2005) Control of excitatory and inhibitory synapse formation by neuroligins. Science 307:1324–1328
Chubykin AA, Atasoy D, Etherton MR, Brose N, Kavalali ET, Gibson JR, Südhof TC (2007) Activity-dependent validation of excitatory versus inhibitory synapses by neuroligin-1 versus neuroligin-2. Neuron 54:919–931
Colino A, Malenka RC (1993) Mechanisms underlying induction of long-term potentiation in rat medial and lateral perforant paths in vitro. J Neurophysiol 69:1150–1159
Cooke SF, Wu J, Plattner F, Errington M, Rowan M, Peters M, Hirano A, Bradshaw KD, Anwyl R, Bliss TVP et al (2006) Autophosphorylation of alphaCaMKII is not a general requirement for NMDA receptor-dependent LTP in the adult mouse. J Physiol 574:805–818
Dahlhaus R, Hines RM, Eadie BD, Kannangara TS, Hines DJ, Brown CE, Christie BR, El-Husseini A (2010) Overexpression of the cell adhesion protein neuroligin-1 induces learning deficits and impairs synaptic plasticity by altering the ratio of excitation to inhibition in the hippocampus. Hippocampus 20:305–322
Giannone G, Mondin M, Grillo-Bosch D, Tessier B, Saint-Michel E, Czöndör K, Sainlos M, Choquet D, Thoumine O (2013) Neurexin-1β binding to neuroligin-1 triggers the preferential recruitment of PSD-95 versus gephyrin through tyrosine phosphorylation of neuroligin-1. Cell Rep 3:1996–2007
Gkogkas CG, Khoutorsky A, Ran I, Rampakakis E, Nevarko T, Weatherill DB, Vasuta C, Yee S, Truitt M, Dallaire P et al (2013) Autism-related deficits via dysregulated eIF4E-dependent translational control. Nature 493:371–377
Heine M, Thoumine O, Mondin M, Tessier B, Giannone G, Choquet D (2008) Activity-independent and subunit-specific recruitment of functional AMPA receptors at neurexin/neuroligin contacts. Proc Natl Acad Sci USA 105:20947–20952
Ichtchenko K, Nguyen T, Südhof TC (1996) Structures, alternative splicing, and neurexin binding of multiple neuroligins. J Biol Chem 271:2676–2682
Jedlicka P, Schwarzacher SW, Winkels R, Kienzler F, Frotscher M, Bramham CR, Schultz C, Bas Orth C, Deller T (2009) Impairment of in vivo theta-burst long-term potentiation and network excitability in the dentate gyrus of synaptopodin-deficient mice lacking the spine apparatus and the cisternal organelle. Hippocampus 19:130–140
Jedlicka P, Deller T, Schwarzacher SW (2010) Computational modeling of GABAA receptor-mediated paired-pulse inhibition in the dentate gyrus. J Comput Neurosci 29:509–519
Jedlicka P, Hoon M, Papadopoulos T, Vlachos A, Winkels R, Poulopoulos A, Betz H, Deller T, Brose N, Varoqueaux F et al (2011a) Increased dentate gyrus excitability in neuroligin-2-deficient mice in vivo. Cereb Cortex 21:357–367
Jedlicka P, Owen M, Vnencak M, Tschäpe J-A, Hick M, Müller UC, Deller T (2011b) Functional consequences of the lack of amyloid precursor protein in the mouse dentate gyrus in vivo. Exp Brain Res 217:441–447
Jones MW, Errington ML, French PJ, Fine A, Bliss TV, Garel S, Charnay P, Bozon B, Laroche S, Davis S (2001) A requirement for the immediate early gene Zif268 in the expression of late LTP and long-term memories. Nat Neurosci 4:289–296
Jung S-Y, Kim J, Bin KO, Jung JH, An K, Jeong AY, Lee CJ, Choi Y-B, Bailey CH, Kandel ER et al (2010) Input-specific synaptic plasticity in the amygdala is regulated by neuroligin-1 via postsynaptic NMDA receptors. Proc Natl Acad Sci USA 107:4710–4715
Kim J, Jung S-Y, Lee YK, Park S, Choi J-S, Lee CJ, Kim H-S, Choi Y-B, Scheiffele P, Bailey CH et al (2008) Neuroligin-1 is required for normal expression of LTP and associative fear memory in the amygdala of adult animals. Proc Natl Acad Sci USA 105:9087–9092
Knight D, Xie W, Boulianne GL (2011) Neurexins and neuroligins: recent insights from invertebrates. Mol Neurobiol 44:426–440
Ko J, Zhang C, Arac D, Boucard AA, Brunger AT, Südhof TC (2009) Neuroligin-1 performs neurexin-dependent and neurexin-independent functions in synapse validation. EMBO J 28:3244–3255
Krueger DD, Tuffy LP, Papadopoulos T, Brose N (2012) The role of neurexins and neuroligins in the formation, maturation, and function of vertebrate synapses. Curr Opin Neurobiol 22:412–422
Kwon H-B, Kozorovitskiy Y, Oh W-J, Peixoto RT, Akhtar N, Saulnier JL, Gu C, Sabatini BL (2012) Neuroligin-1-dependent competition regulates cortical synaptogenesis and synapse number. Nat Neurosci 15:1667–1674
Lømo T (2009) Excitability changes within transverse lamellae of dentate granule cells and their longitudinal spread following orthodromic or antidromic activation. Hippocampus 19:633–648
Marder CP, Buonomano DV (2004) Timing and balance of inhibition enhance the effect of long-term potentiation on cell firing. J Neurosci 24:8873–8884
Mondin M, Labrousse V, Hosy E, Heine M, Tessier B, Levet F, Poujol C, Blanchet C, Choquet D, Thoumine O (2011) Neurexin–neuroligin adhesions capture surface-diffusing AMPA receptors through PSD-95 scaffolds. J Neurosci 31:13500–13515
Nakashiba T, Cushman JD, Pelkey KA, Renaudineau S, Buhl DL, McHugh TJ, Rodriguez Barrera V, Chittajallu R, Iwamoto KS, McBain CJ et al (2012) Young dentate granule cells mediate pattern separation, whereas old granule cells facilitate pattern completion. Cell 149:188–201
Nam CI, Chen L (2005) Postsynaptic assembly induced by neurexin-neuroligin interaction and neurotransmitter. Proc Natl Acad Sci USA 102:6137–6142
Nicoll RA, Roche KW (2013) Long-term potentiation: peeling the onion. Neuropharmacology. doi:10.1016/j.neuropharm.2013.02.010
Prange O, Wong TP, Gerrow K, Wang YT, El-Husseini A (2004) A balance between excitatory and inhibitory synapses is controlled by PSD-95 and neuroligin. Proc Natl Acad Sci USA 101:13915–13920
Schapitz IU, Behrend B, Pechmann Y, Lappe-Siefke C, Kneussel SJ, Wallace KE, Stempel AV, Buck F, Grant SGN, Schweizer M et al (2010) Neuroligin 1 is dynamically exchanged at postsynaptic sites. J Neurosci 30:12733–12744
Schmeisser MJ, Ey E, Wegener S, Bockmann J, Stempel AV, Kuebler A, Janssen A-L, Udvardi PT, Shiban E, Spilker C et al (2012) Autistic-like behaviours and hyperactivity in mice lacking ProSAP1/Shank2. Nature 486:256–260
Schnell E, Bensen AL, Washburn EK, Westbrook GL (2012) Neuroligin-1 overexpression in newborn granule cells in vivo. PLoS ONE 7:e48045
Seabrook GR, Smith DW, Bowery BJ, Easter A, Reynolds T, Fitzjohn SM, Morton RA, Zheng H, Dawson GR, Sirinathsinghji DJ et al (1999) Mechanisms contributing to the deficits in hippocampal synaptic plasticity in mice lacking amyloid precursor protein. Neuropharmacology 38:349–359
Shipman SL, Nicoll RA (2012) A subtype-specific function for the extracellular domain of neuroligin 1 in hippocampal LTP. Neuron 76:309–316
Shipman SL, Schnell E, Hirai T, Chen B-S, Roche KW, Nicoll RA (2011) Functional dependence of neuroligin on a new non-PDZ intracellular domain. Nat Neurosci 14:718–726
Sloviter RS (1991) Feedforward and feedback inhibition of hippocampal principal cell activity evoked by perforant path stimulation: GABA-mediated mechanisms that regulate excitability in vivo. Hippocampus 1:31–40
Soler-Llavina GJ, Fuccillo MV, Ko J, Südhof TC, Malenka RC (2011) The neurexin ligands, neuroligins and leucine-rich repeat transmembrane proteins, perform convergent and divergent synaptic functions in vivo. Proc Natl Acad Sci USA 108:16502–16509
Song JY, Ichtchenko K, Südhof TC, Brose N (1999) Neuroligin 1 is a postsynaptic cell-adhesion molecule of excitatory synapses. Proc Natl Acad Sci USA 96:1100–1105
Südhof TC (2008) Neuroligins and neurexins link synaptic function to cognitive disease. Nature 455:903–911
Varoqueaux F, Aramuni G, Rawson RL, Mohrmann R, Missler M, Gottmann K, Zhang W, Südhof TC, Brose N (2006) Neuroligins determine synapse maturation and function. Neuron 51:741–754
Wathey JC, Lytton WW, Jester JM, Sejnowski TJ (1992) Computer simulations of EPSP-spike (E–S) potentiation in hippocampal CA1 pyramidal cells. J Neurosci 12:607–618
Wittenmayer N, Körber C, Liu H, Kremer T, Varoqueaux F, Chapman ER, Brose N, Kuner T, Dresbach T (2009) Postsynaptic Neuroligin1 regulates presynaptic maturation. Proc Natl Acad Sci USA 106:13564–13569
Yang M, Bozdagi O, Scattoni ML, Wöhr M, Roullet FI, Katz AM, Abrams DN, Kalikhman D, Simon H, Woldeyohannes L et al (2012) Reduced excitatory neurotransmission and mild autism-relevant phenotypes in adolescent Shank3 null mutant mice. J Neurosci 32:6525–6541
Zeidan A, Ziv NE (2012) Neuroligin-1 loss is associated with reduced tenacity of excitatory synapses. PLoS ONE 7:e42314