TY - JOUR AB - Loss-of-function mutations in the synaptic adhesion protein Neuroligin-4 are among the most common genetic abnormalities associated with autism spectrum disorders, but little is known about the function of Neuroligin-4 and the consequences of its loss. We assessed synaptic and network characteristics in Neuroligin-4 knockout mice, focusing on the hippocampus as a model brain region with a critical role in cognition and memory, and found that Neuroligin-4 deletion causes subtle defects of the protein composition and function of GABAergic synapses in the hippocampal CA3 region. Interestingly, these subtle synaptic changes are accompanied by pronounced perturbations of γ-oscillatory network activity, which has been implicated in cognitive function and is altered in multiple psychiatric and neurodevelopmental disorders. Our data provide important insights into the mechanisms by which Neuroligin-4-dependent GABAergic synapses may contribute to autism phenotypes and indicate new strategies for therapeutic approaches. AU - Hammer, Matthieu AU - Krueger Burg, Dilja AU - Tuffy, Liam AU - Cooper, Benjamin AU - Taschenberger, Holger AU - Goswami, Sarit AU - Ehrenreich, Hannelore AU - Jonas, Peter M AU - Varoqueaux, Frederique AU - Rhee, Jeong AU - Brose, Nils ID - 1615 IS - 3 JF - Cell Reports TI - Perturbed hippocampal synaptic inhibition and γ-oscillations in a neuroligin-4 knockout mouse model of autism VL - 13 ER - TY - JOUR AB - Spontaneous postsynaptic currents (PSCs) provide key information about the mechanisms of synaptic transmission and the activity modes of neuronal networks. However, detecting spontaneous PSCs in vitro and in vivo has been challenging, because of the small amplitude, the variable kinetics, and the undefined time of generation of these events. Here, we describe a, to our knowledge, new method for detecting spontaneous synaptic events by deconvolution, using a template that approximates the average time course of spontaneous PSCs. A recorded PSC trace is deconvolved from the template, resulting in a series of delta-like functions. The maxima of these delta-like events are reliably detected, revealing the precise onset times of the spontaneous PSCs. Among all detection methods, the deconvolution-based method has a unique temporal resolution, allowing the detection of individual events in high-frequency bursts. Furthermore, the deconvolution-based method has a high amplitude resolution, because deconvolution can substantially increase the signal/noise ratio. When tested against previously published methods using experimental data, the deconvolution-based method was superior for spontaneous PSCs recorded in vivo. Using the high-resolution deconvolution-based detection algorithm, we show that the frequency of spontaneous excitatory postsynaptic currents in dentate gyrus granule cells is 4.5 times higher in vivo than in vitro. AU - Pernia-Andrade, Alejandro AU - Goswami, Sarit AU - Stickler, Yvonne AU - Fröbe, Ulrich AU - Schlögl, Alois AU - Jonas, Peter M ID - 2954 IS - 7 JF - Biophysical Journal TI - A deconvolution based method with high sensitivity and temporal resolution for detection of spontaneous synaptic currents in vitro and in vivo VL - 103 ER - TY - JOUR AB - The coupling between presynaptic Ca^(2+) channels and Ca^(2+) sensors of exocytosis is a key determinant of synaptic transmission. Evoked release from parvalbumin (PV)-expressing interneurons is triggered by nanodomain coupling of P/Q-type Ca^(2+) channels, whereas release from cholecystokinin (CCK)-containing interneurons is generated by microdomain coupling of N-type channels. Nanodomain coupling has several functional advantages, including speed and efficacy of transmission. One potential disadvantage is that stochastic opening of presynaptic Ca^(2+) channels may trigger spontaneous transmitter release. We addressed this possibility in rat hippocampal granule cells, which receive converging inputs from different inhibitory sources. Both reduction of extracellular Ca^(2+) concentration and the unselective Ca^(2+) channel blocker Cd^(2+) reduced the frequency of miniature IPSCs (mIPSCs) in granule cells by ~50%, suggesting that the opening of presynaptic Ca^(2+) channels contributes to spontaneous release. Application of the selective P/Q-type Ca^(2+) channel blocker ω-agatoxin IVa had no detectable effects, whereas both the N-type blocker ω-conotoxin GVIa and the L-type blocker nimodipine reduced mIPSC frequency. Furthermore, both the fast Ca^(2+) chelator BAPTA-AM and the slow chelator EGTA-AM reduced the mIPSC frequency, suggesting that Ca^(2+)-dependent spontaneous release is triggered by microdomain rather than nanodomain coupling. The CB_(1) receptor agonist WIN 55212-2 also decreased spontaneous release; this effect was occluded by prior application of ω-conotoxin GVIa, suggesting that a major fraction of Ca^(2+)-dependent spontaneous release was generated at the terminals of CCK-expressing interneurons. Tonic inhibition generated by spontaneous opening of presynaptic N- and L-type Ca^(2+) channels may be important for hippocampal information processing. AU - Goswami, Sarit AU - Bucurenciu, Iancu AU - Jonas, Peter M ID - 2969 IS - 41 JF - Journal of Neuroscience TI - Miniature IPSCs in hippocampal granule cells are triggered by voltage-gated Ca^(2+) channels via microdomain coupling VL - 32 ER - TY - JOUR AB - The physical distance between presynaptic Ca2+ channels and the Ca2+ sensors that trigger exocytosis of neurotransmitter-containing vesicles is a key determinant of the signalling properties of synapses in the nervous system. Recent functional analysis indicates that in some fast central synapses, transmitter release is triggered by a small number of Ca2+ channels that are coupled to Ca2+ sensors at the nanometre scale. Molecular analysis suggests that this tight coupling is generated by protein–protein interactions involving Ca2+ channels, Ca2+ sensors and various other synaptic proteins. Nanodomain coupling has several functional advantages, as it increases the efficacy, speed and energy efficiency of synaptic transmission. AU - Eggermann, Emmanuel AU - Bucurenciu, Iancu AU - Goswami, Sarit AU - Jonas, Peter M ID - 3317 IS - 1 JF - Nature Reviews Neuroscience TI - Nanodomain coupling between Ca(2+) channels and sensors of exocytosis at fast mammalian synapses VL - 13 ER - TY - JOUR AB - Olfactory responses of Drosophila undergo pronounced changes after eclosion. The flies develop attraction to odors to which they are exposed and aversion to other odors. Behavioral adaptation is correlated with changes in the firing pattern of olfactory receptor neurons (ORNs). In this article, we present an information-theoretic analysis of the firing pattern of ORNs. Flies reared in a synthetic odorless medium were transferred after eclosion to three different media: (i) a synthetic medium relatively devoid of odor cues, (ii) synthetic medium infused with a single odorant, and (iii) complex cornmeal medium rich in odors. Recordings were made from an identified sensillum (type II), and the Jensen-Shannon divergence (D(JS)) was used to assess quantitatively the differences between ensemble spike responses to different odors. Analysis shows that prolonged exposure to ethyl acetate and several related esters increases sensitivity to these esters but does not improve the ability of the fly to distinguish between them. Flies exposed to cornmeal display varied sensitivity to these odorants and at the same time develop greater capacity to distinguish between odors. Deprivation of odor experience on an odorless synthetic medium leads to a loss of both sensitivity and acuity. Rich olfactory experience thus helps to shape the ORNs response and enhances its discriminative power. The experiments presented here demonstrate an experience-dependent adaptation at the level of the receptor neuron. AU - Iyengar, Atulya AU - Chakraborty Tuhin, Subhra AU - Sarit Goswami AU - Wu, Chun Fang AU - Siddiqi, Obaid ID - 3294 IS - 21 JF - PNAS TI - Post eclosion odor experience modifies olfactory receptor neuron coding in Drosophila VL - 107 ER - TY - JOUR AB - Chemotactic responses of Drosophila to certain esters and alcohols are experience dependent. When the flies are exposed after eclosion to these chemicals, the odorants become strongly attractive. We show that behavioral conditioning is accompanied by an increase in the electrophysiological responses of single neurons in sensilla basiconica. Sensitization involves odorants that act on a common olfactory receptor. The possible mechanism of imaginal conditioning and its ecological and evolutionary significance are discussed. AU - Chakraborty Tuhin, Subhra AU - Sarit Goswami AU - Siddiqi, Obaid ID - 3293 IS - 1-2 JF - Journal of Neurogenetics TI - Sensory correlates of imaginal conditioning in Drosophila melanogaster VL - 23 ER -