caa a22 4500 606201165 CHVBK 20210128100947.0 cr unu---uuuuu 210128e20150101xx s 000 0 eng 10.1007/s00429-013-0636-1 doi (NATIONALLICENCE)springer-10.1007/s00429-013-0636-1 Neuroligin-1 regulates excitatory synaptic transmission, LTP and EPSP-spike coupling in the dentate gyrus in vivo [Elektronische Daten] [Peter Jedlicka, Matej Vnencak, Dilja Krueger, Tassilo Jungenitz, Nils Brose, Stephan Schwarzacher] 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. Springer-Verlag Berlin Heidelberg, 2013 Dentate granule cells nationallicence Perforant path nationallicence Excitability nationallicence Synaptic plasticity nationallicence Paired-pulse inhibition nationallicence Cell adhesion molecule nationallicence Jedlicka Peter Institute of Clinical Neuroanatomy, Neuroscience Center, Goethe-University Frankfurt, Theodor-Stern Kai 7, 60590, Frankfurt, Germany aut Vnencak Matej Institute of Clinical Neuroanatomy, Neuroscience Center, Goethe-University Frankfurt, Theodor-Stern Kai 7, 60590, Frankfurt, Germany aut Krueger Dilja Department of Molecular Neurobiology, Max Planck Institute of Experimental Medicine, 37075, Göttingen, Germany aut Jungenitz Tassilo Institute of Clinical Neuroanatomy, Neuroscience Center, Goethe-University Frankfurt, Theodor-Stern Kai 7, 60590, Frankfurt, Germany aut Brose Nils Department of Molecular Neurobiology, Max Planck Institute of Experimental Medicine, 37075, Göttingen, Germany aut Schwarzacher Stephan Institute of Clinical Neuroanatomy, Neuroscience Center, Goethe-University Frankfurt, Theodor-Stern Kai 7, 60590, Frankfurt, Germany aut Brain Structure and Function Springer Berlin Heidelberg 220/1(2015-01-01), 47-58 1863-2653 220:1<47 2015 220 429 https://doi.org/10.1007/s00429-013-0636-1 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00429-013-0636-1 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Jedlicka Peter Institute of Clinical Neuroanatomy, Neuroscience Center, Goethe-University Frankfurt, Theodor-Stern Kai 7, 60590, Frankfurt, Germany aut NATIONALLICENCE 700 1- Vnencak Matej Institute of Clinical Neuroanatomy, Neuroscience Center, Goethe-University Frankfurt, Theodor-Stern Kai 7, 60590, Frankfurt, Germany aut NATIONALLICENCE 700 1- Krueger Dilja Department of Molecular Neurobiology, Max Planck Institute of Experimental Medicine, 37075, Göttingen, Germany aut NATIONALLICENCE 700 1- Jungenitz Tassilo Institute of Clinical Neuroanatomy, Neuroscience Center, Goethe-University Frankfurt, Theodor-Stern Kai 7, 60590, Frankfurt, Germany aut NATIONALLICENCE 700 1- Brose Nils Department of Molecular Neurobiology, Max Planck Institute of Experimental Medicine, 37075, Göttingen, Germany aut NATIONALLICENCE 700 1- Schwarzacher Stephan Institute of Clinical Neuroanatomy, Neuroscience Center, Goethe-University Frankfurt, Theodor-Stern Kai 7, 60590, Frankfurt, Germany aut NATIONALLICENCE 773 0- Brain Structure and Function Springer Berlin Heidelberg 220/1(2015-01-01), 47-58 1863-2653 220:1<47 2015 220 429