@article{1614, abstract = {GABAergic perisoma-inhibiting fast-spiking interneurons (PIIs) effectively control the activity of large neuron populations by their wide axonal arborizations. It is generally assumed that the output of one PII to its target cells is strong and rapid. Here, we show that, unexpectedly, both strength and time course of PII-mediated perisomatic inhibition change with distance between synaptically connected partners in the rodent hippocampus. Synaptic signals become weaker due to lower contact numbers and decay more slowly with distance, very likely resulting from changes in GABAA receptor subunit composition. When distance-dependent synaptic inhibition is introduced to a rhythmically active neuronal network model, randomly driven principal cell assemblies are strongly synchronized by the PIIs, leading to higher precision in principal cell spike times than in a network with uniform synaptic inhibition. }, author = {Strüber, Michael and Jonas, Peter M and Bartos, Marlene}, journal = {PNAS}, number = {4}, pages = {1220 -- 1225}, publisher = {National Academy of Sciences}, title = {{Strength and duration of perisomatic GABAergic inhibition depend on distance between synaptically connected cells}}, doi = {10.1073/pnas.1412996112}, volume = {112}, year = {2015}, } @article{1845, abstract = {Based on extrapolation from excitatory synapses, it is often assumed that depletion of the releasable pool of synaptic vesicles is the main factor underlying depression at inhibitory synapses. In this issue of Neuron, using subcellular patch-clamp recording from inhibitory presynaptic terminals, Kawaguchi and Sakaba (2015) show that at Purkinje cell-deep cerebellar nuclei neuron synapses, changes in presynaptic action potential waveform substantially contribute to synaptic depression. Based on extrapolation from excitatory synapses, it is often assumed that depletion of the releasable pool of synaptic vesicles is the main factor underlying depression at inhibitory synapses. In this issue of Neuron, using subcellular patch-clamp recording from inhibitory presynaptic terminals, Kawaguchi and Sakaba (2015) show that at Purkinje cell-deep cerebellar nuclei neuron synapses, changes in presynaptic action potential waveform substantially contribute to synaptic depression.}, author = {Vandael, David H and Espinoza Martinez, Claudia and Jonas, Peter M}, journal = {Neuron}, number = {6}, pages = {1149 -- 1151}, publisher = {Elsevier}, title = {{Excitement about inhibitory presynaptic terminals}}, doi = {10.1016/j.neuron.2015.03.006}, volume = {85}, year = {2015}, } @article{1834, abstract = {Huge body of evidences demonstrated that volatile anesthetics affect the hippocampal neurogenesis and neurocognitive functions, and most of them showed impairment at anesthetic dose. Here, we investigated the effect of low dose (1.8%) sevoflurane on hippocampal neurogenesis and dentate gyrus-dependent learning. Neonatal rats at postnatal day 4 to 6 (P4-6) were treated with 1.8% sevoflurane for 6 hours. Neurogenesis was quantified by bromodeoxyuridine labeling and electrophysiology recording. Four and seven weeks after treatment, the Morris water maze and contextual-fear discrimination learning tests were performed to determine the influence on spatial learning and pattern separation. A 6-hour treatment with 1.8% sevoflurane promoted hippocampal neurogenesis and increased the survival of newborn cells and the proportion of immature granular cells in the dentate gyrus of neonatal rats. Sevoflurane-treated rats performed better during the training days of the Morris water maze test and in contextual-fear discrimination learning test. These results suggest that a subanesthetic dose of sevoflurane promotes hippocampal neurogenesis in neonatal rats and facilitates their performance in dentate gyrus-dependent learning tasks.}, author = {Chen, Chong and Wang, Chao and Zhao, Xuan and Zhou, Tao and Xu, Dao and Wang, Zhi and Wang, Ying}, journal = {ASN Neuro}, number = {2}, publisher = {SAGE Publications}, title = {{Low-dose sevoflurane promoteshippocampal neurogenesis and facilitates the development of dentate gyrus-dependent learning in neonatal rats}}, doi = {10.1177/1759091415575845}, volume = {7}, year = {2015}, } @article{1890, abstract = {To search for a target in a complex environment is an everyday behavior that ends with finding the target. When we search for two identical targets, however, we must continue the search after finding the first target and memorize its location. We used fixation-related potentials to investigate the neural correlates of different stages of the search, that is, before and after finding the first target. Having found the first target influenced subsequent distractor processing. Compared to distractor fixations before the first target fixation, a negative shift was observed for three subsequent distractor fixations. These results suggest that processing a target in continued search modulates the brain's response, either transiently by reflecting temporary working memory processes or permanently by reflecting working memory retention.}, author = {Körner, Christof and Braunstein, Verena and Stangl, Matthias and Schlögl, Alois and Neuper, Christa and Ischebeck, Anja}, journal = {Psychophysiology}, number = {4}, pages = {385 -- 395}, publisher = {Wiley-Blackwell}, title = {{Sequential effects in continued visual search: Using fixation-related potentials to compare distractor processing before and after target detection}}, doi = {10.1111/psyp.12062}, volume = {51}, year = {2014}, } @article{2002, abstract = {Oriens-lacunosum moleculare (O-LM) interneurons in the CA1 region of the hippocampus play a key role in feedback inhibition and in the control of network activity. However, how these cells are efficiently activated in the network remains unclear. To address this question, I performed recordings from CA1 pyramidal neuron axons, the presynaptic fibers that provide feedback innervation of these interneurons. Two forms of axonal action potential (AP) modulation were identified. First, repetitive stimulation resulted in activity-dependent AP broadening. Broadening showed fast onset, with marked changes in AP shape following a single AP. Second, tonic depolarization in CA1 pyramidal neuron somata induced AP broadening in the axon, and depolarization-induced broadening summated with activity-dependent broadening. Outsideout patch recordings from CA1 pyramidal neuron axons revealed a high density of a-dendrotoxin (α-DTX)-sensitive, inactivating K+ channels, suggesting that K+ channel inactivation mechanistically contributes to AP broadening. To examine the functional consequences of axonal AP modulation for synaptic transmission, I performed paired recordings between synaptically connected CA1 pyramidal neurons and O-LM interneurons. CA1 pyramidal neuron-O-LM interneuron excitatory postsynaptic currents (EPSCs) showed facilitation during both repetitive stimulation and tonic depolarization of the presynaptic neuron. Both effects were mimicked and occluded by α-DTX, suggesting that they were mediated by K+ channel inactivation. Therefore, axonal AP modulation can greatly facilitate the activation of O-LM interneurons. In conclusion, modulation of AP shape in CA1 pyramidal neuron axons substantially enhances the efficacy of principal neuron-interneuron synapses, promoting the activation of O-LM interneurons in recurrent inhibitory microcircuits.}, author = {Kim, Sooyun}, journal = {PLoS One}, number = {11}, publisher = {Public Library of Science}, title = {{Action potential modulation in CA1 pyramidal neuron axons facilitates OLM interneuron activation in recurrent inhibitory microcircuits of rat hippocampus}}, doi = {10.1371/journal.pone.0113124}, volume = {9}, year = {2014}, } @article{2031, abstract = {A puzzling property of synaptic transmission, originally established at the neuromuscular junction, is that the time course of transmitter release is independent of the extracellular Ca2+ concentration ([Ca2+]o), whereas the rate of release is highly [Ca2+]o-dependent. Here, we examine the time course of release at inhibitory basket cell-Purkinje cell synapses and show that it is independent of [Ca2+]o. Modeling of Ca2+-dependent transmitter release suggests that the invariant time course of release critically depends on tight coupling between Ca2+ channels and release sensors. Experiments with exogenous Ca2+ chelators reveal that channel-sensor coupling at basket cell-Purkinje cell synapses is very tight, with a mean distance of 10–20 nm. Thus, tight channel-sensor coupling provides a mechanistic explanation for the apparent [Ca2+]o independence of the time course of release.}, author = {Arai, Itaru and Jonas, Peter M}, journal = {eLife}, publisher = {eLife Sciences Publications}, title = {{Nanodomain coupling explains Ca^2+ independence of transmitter release time course at a fast central synapse}}, doi = {10.7554/eLife.04057}, volume = {3}, year = {2014}, } @article{2041, abstract = {The hippocampus mediates several higher brain functions, such as learning, memory, and spatial coding. The input region of the hippocampus, the dentate gyrus, plays a critical role in these processes. Several lines of evidence suggest that the dentate gyrus acts as a preprocessor of incoming information, preparing it for subsequent processing in CA3. For example, the dentate gyrus converts input from the entorhinal cortex, where cells have multiple spatial fields, into the spatially more specific place cell activity characteristic of the CA3 region. Furthermore, the dentate gyrus is involved in pattern separation, transforming relatively similar input patterns into substantially different output patterns. Finally, the dentate gyrus produces a very sparse coding scheme in which only a very small fraction of neurons are active at any one time.}, author = {Jonas, Peter M and Lisman, John}, journal = {Frontiers in Neural Circuits}, publisher = {Frontiers Research Foundation}, title = {{Structure, function and plasticity of hippocampal dentate gyrus microcircuits}}, doi = {10.3389/fncir.2014.00107}, volume = {8}, year = {2014}, } @article{2062, abstract = {The success story of fast-spiking, parvalbumin-positive (PV+) GABAergic interneurons (GABA, γ-aminobutyric acid) in the mammalian central nervous system is noteworthy. In 1995, the properties of these interneurons were completely unknown. Twenty years later, thanks to the massive use of subcellular patch-clamp techniques, simultaneous multiple-cell recording, optogenetics, in vivo measurements, and computational approaches, our knowledge about PV+ interneurons became more extensive than for several types of pyramidal neurons. These findings have implications beyond the “small world” of basic research on GABAergic cells. For example, the results provide a first proof of principle that neuroscientists might be able to close the gaps between the molecular, cellular, network, and behavioral levels, representing one of the main challenges at the present time. Furthermore, the results may form the basis for PV+ interneurons as therapeutic targets for brain disease in the future. However, much needs to be learned about the basic function of these interneurons before clinical neuroscientists will be able to use PV+ interneurons for therapeutic purposes.}, author = {Hu, Hua and Gan, Jian and Jonas, Peter M}, journal = {Science}, number = {6196}, publisher = {American Association for the Advancement of Science}, title = {{Fast-spiking parvalbumin^+ GABAergic interneurons: From cellular design to microcircuit function}}, doi = {10.1126/science.1255263}, volume = {345}, year = {2014}, } @article{2164, abstract = {Neuronal ectopia, such as granule cell dispersion (GCD) in temporal lobe epilepsy (TLE), has been assumed to result from a migration defect during development. Indeed, recent studies reported that aberrant migration of neonatal-generated dentate granule cells (GCs) increased the risk to develop epilepsy later in life. On the contrary, in the present study, we show that fully differentiated GCs become motile following the induction of epileptiform activity, resulting in GCD. Hippocampal slice cultures from transgenic mice expressing green fluorescent protein in differentiated, but not in newly generated GCs, were incubated with the glutamate receptor agonist kainate (KA), which induced GC burst activity and GCD. Using real-time microscopy, we observed that KA-exposed, differentiated GCs translocated their cell bodies and changed their dendritic organization. As found in human TLE, KA application was associated with decreased expression of the extracellular matrix protein Reelin, particularly in hilar interneurons. Together these findings suggest that KA-induced motility of differentiated GCs contributes to the development of GCD and establish slice cultures as a model to study neuronal changes induced by epileptiform activity. }, author = {Chai, Xuejun and Münzner, Gert and Zhao, Shanting and Tinnes, Stefanie and Kowalski, Janina and Häussler, Ute and Young, Christina and Haas, Carola and Frotscher, Michael}, journal = {Cerebral Cortex}, number = {8}, pages = {2130 -- 2140}, publisher = {Oxford University Press}, title = {{Epilepsy-induced motility of differentiated neurons}}, doi = {10.1093/cercor/bht067}, volume = {24}, year = {2014}, } @article{2176, abstract = {Electron microscopy (EM) allows for the simultaneous visualization of all tissue components at high resolution. However, the extent to which conventional aldehyde fixation and ethanol dehydration of the tissue alter the fine structure of cells and organelles, thereby preventing detection of subtle structural changes induced by an experiment, has remained an issue. Attempts have been made to rapidly freeze tissue to preserve native ultrastructure. Shock-freezing of living tissue under high pressure (high-pressure freezing, HPF) followed by cryosubstitution of the tissue water avoids aldehyde fixation and dehydration in ethanol; the tissue water is immobilized in â ̂1/450 ms, and a close-to-native fine structure of cells, organelles and molecules is preserved. Here we describe a protocol for HPF that is useful to monitor ultrastructural changes associated with functional changes at synapses in the brain but can be applied to many other tissues as well. The procedure requires a high-pressure freezer and takes a minimum of 7 d but can be paused at several points.}, author = {Studer, Daniel and Zhao, Shanting and Chai, Xuejun and Jonas, Peter M and Graber, Werner and Nestel, Sigrun and Frotscher, Michael}, journal = {Nature Protocols}, number = {6}, pages = {1480 -- 1495}, publisher = {Nature Publishing Group}, title = {{Capture of activity-induced ultrastructural changes at synapses by high-pressure freezing of brain tissue}}, doi = {10.1038/nprot.2014.099}, volume = {9}, year = {2014}, }