nach oben

Brain Structure and Function

Erschienen in:

01.01.2015 | Original Article

Neuroligin-1 regulates excitatory synaptic transmission, LTP and EPSP-spike coupling in the dentate gyrus in vivo

verfasst von: Peter Jedlicka, Matej Vnencak, Dilja D. Krueger, Tassilo Jungenitz, Nils Brose, Stephan W. Schwarzacher

Erschienen in: Brain Structure and Function | Ausgabe 1/2015

Einloggen, um Zugang zu erhalten

Abstract

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.

Nur mit Berechtigung zugänglich

Abraham WC, Gustafsson B, Wigström H (1987) Long-term potentiation involves enhanced synaptic excitation relative to synaptic inhibition in guinea-pig hippocampus. J Physiol 394:367–380PubMedCentralPubMedCrossRef

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 32:14966–14978PubMedCentralPubMedCrossRef

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 30:2115–2129PubMedCentralPubMedCrossRef

Bourgeron T (2009) A synaptic trek to autism. Curr Opin Neurobiol 19:231–234PubMedCrossRef

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 22:1363–1370PubMedCentralPubMedCrossRef

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 110:725–730PubMedCentralPubMedCrossRef

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 86:831–845PubMedCrossRef

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 67:967–983PubMedCrossRef

Chih B, Engelman H, Scheiffele P (2005) Control of excitatory and inhibitory synapse formation by neuroligins. Science 307:1324–1328PubMedCrossRef

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 54:919–931PubMedCentralPubMedCrossRef

Colino A, Malenka RC (1993) Mechanisms underlying induction of long-term potentiation in rat medial and lateral perforant paths in vitro. J Neurophysiol 69:1150–1159PubMed

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 574:805–818PubMedCentralPubMedCrossRef

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 20:305–322PubMedCrossRef

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 3:1996–2007PubMedCrossRef

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 493:371–377PubMedCentralPubMedCrossRef

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 105:20947–20952PubMedCentralPubMedCrossRef

Ichtchenko K, Nguyen T, Südhof TC (1996) Structures, alternative splicing, and neurexin binding of multiple neuroligins. J Biol Chem 271:2676–2682PubMedCrossRef

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 19:130–140PubMedCrossRef

Jedlicka P, Deller T, Schwarzacher SW (2010) Computational modeling of GABAA receptor-mediated paired-pulse inhibition in the dentate gyrus. J Comput Neurosci 29:509–519PubMedCrossRef

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 21:357–367PubMedCrossRef

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 217:441–447PubMedCrossRef

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 4:289–296PubMedCrossRef

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 107:4710–4715PubMedCentralPubMedCrossRef

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 105:9087–9092PubMedCentralPubMedCrossRef

Knight D, Xie W, Boulianne GL (2011) Neurexins and neuroligins: recent insights from invertebrates. Mol Neurobiol 44:426–440PubMedCentralPubMedCrossRef

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 28:3244–3255PubMedCentralPubMedCrossRef

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 22:412–422PubMedCrossRef

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 15:1667–1674PubMedCentralPubMedCrossRef

Lømo T (2009) Excitability changes within transverse lamellae of dentate granule cells and their longitudinal spread following orthodromic or antidromic activation. Hippocampus 19:633–648PubMedCrossRef

Marder CP, Buonomano DV (2004) Timing and balance of inhibition enhance the effect of long-term potentiation on cell firing. J Neurosci 24:8873–8884PubMedCrossRef

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 31:13500–13515PubMedCrossRef

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 149:188–201PubMedCentralPubMedCrossRef

Nam CI, Chen L (2005) Postsynaptic assembly induced by neurexin-neuroligin interaction and neurotransmitter. Proc Natl Acad Sci USA 102:6137–6142PubMedCentralPubMedCrossRef

Nicoll RA, Roche KW (2013) Long-term potentiation: peeling the onion. Neuropharmacology. doi:10.1016/j.neuropharm.2013.02.010 PubMedCentralPubMed

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 101:13915–13920PubMedCentralPubMedCrossRef

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 30:12733–12744PubMedCentralPubMedCrossRef

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 486:256–260PubMed

Schnell E, Bensen AL, Washburn EK, Westbrook GL (2012) Neuroligin-1 overexpression in newborn granule cells in vivo. PLoS ONE 7:e48045PubMedCentralPubMedCrossRef

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 38:349–359PubMedCrossRef

Shipman SL, Nicoll RA (2012) A subtype-specific function for the extracellular domain of neuroligin 1 in hippocampal LTP. Neuron 76:309–316PubMedCentralPubMedCrossRef

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 14:718–726PubMedCentralPubMedCrossRef

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 1:31–40PubMedCrossRef

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 108:16502–16509PubMedCentralPubMedCrossRef

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 96:1100–1105PubMedCentralPubMedCrossRef

Südhof TC (2008) Neuroligins and neurexins link synaptic function to cognitive disease. Nature 455:903–911PubMedCentralPubMedCrossRef

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 51:741–754PubMedCrossRef

Wathey JC, Lytton WW, Jester JM, Sejnowski TJ (1992) Computer simulations of EPSP-spike (E–S) potentiation in hippocampal CA1 pyramidal cells. J Neurosci 12:607–618PubMed

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 106:13564–13569PubMedCentralPubMedCrossRef

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 32:6525–6541PubMedCentralPubMedCrossRef

Zeidan A, Ziv NE (2012) Neuroligin-1 loss is associated with reduced tenacity of excitatory synapses. PLoS ONE 7:e42314PubMedCentralPubMedCrossRef

Titel: Neuroligin-1 regulates excitatory synaptic transmission, LTP and EPSP-spike coupling in the dentate gyrus in vivo
verfasst von: Peter Jedlicka
Matej Vnencak
Dilja D. Krueger
Tassilo Jungenitz
Nils Brose
Stephan W. Schwarzacher
Publikationsdatum: 01.01.2015
Verlag: Springer Berlin Heidelberg
Erschienen in: Brain Structure and Function / Ausgabe 1/2015
Print ISSN: 1863-2653
Elektronische ISSN: 1863-2661
DOI: https://doi.org/10.1007/s00429-013-0636-1

Leitlinien kompakt für die Neurologie

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Neu im Fachgebiet Neurologie

23.04.2024 | Demenz | Nachrichten

Update Neurologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Springer Medizin

Neuroligin-1 regulates excitatory synaptic transmission, LTP and EPSP-spike coupling in the dentate gyrus in vivo

Abstract

Leitlinien kompakt für die Neurologie

Neu im Fachgebiet Neurologie

Demenzkranke durch Antipsychotika vielfach gefährdet

Parkinson-Therapie im Wandel – aktuelle Leitlinie im Fokus

Auf diese Krankheiten bei Geflüchteten sollten Sie vorbereitet sein

Hustenstiller lindert Agitation bei Alzheimer

Update Neurologie

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 1/2015

MeCP2-mediated alterations of striatal features accompany psychomotor deficits in a mouse model of Rett syndrome

Multivariate classification of social anxiety disorder using whole brain functional connectivity

Enhanced characterization of the zebrafish brain as revealed by super-resolution track-density imaging

Onset-related differences in neural substrates of tinnitus-related distress: the anterior cingulate cortex in late-onset tinnitus, and the frontal cortex in early-onset tinnitus

The multispecific thyroid hormone transporter OATP1C1 mediates cell-specific sulforhodamine 101-labeling of hippocampal astrocytes

Dynamic brain functional connectivity modulated by resting-state networks

Leitlinien kompakt für die Neurologie

Neu im Fachgebiet Neurologie

Demenzkranke durch Antipsychotika vielfach gefährdet

Parkinson-Therapie im Wandel – aktuelle Leitlinie im Fokus

Auf diese Krankheiten bei Geflüchteten sollten Sie vorbereitet sein

Hustenstiller lindert Agitation bei Alzheimer

Update Neurologie