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Joachim H. R. Lübke

Bio: Joachim H. R. Lübke is an academic researcher from RWTH Aachen University. The author has contributed to research in topics: Neocortex & Synaptic vesicle. The author has an hindex of 37, co-authored 72 publications receiving 11005 citations. Previous affiliations of Joachim H. R. Lübke include Forschungszentrum Jülich & University of Freiburg.


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Journal ArticleDOI
10 Jan 1997-Science
TL;DR: In dual whole-cell voltage recordings from pyramidal neurons, the coincidence of post Synaptic action potentials and unitary excitatory postsynaptic potentials was found to induce changes in EPSPs.
Abstract: Activity-driven modifications in synaptic connections between neurons in the neocortex may occur during development and learning In dual whole-cell voltage recordings from pyramidal neurons, the coincidence of postsynaptic action potentials (APs) and unitary excitatory postsynaptic potentials (EPSPs) was found to induce changes in EPSPs Their average amplitudes were differentially up- or down-regulated, depending on the precise timing of postsynaptic APs relative to EPSPs These observations suggest that APs propagating back into dendrites serve to modify single active synaptic connections, depending on the pattern of electrical activity in the pre- and postsynaptic neurons

3,591 citations

Journal ArticleDOI
TL;DR: In this article, dual voltage recordings were made from pairs of adjacent, synaptically connected pyramidal neurones in brain slices of young rat (14-16 days) somatosensory cortex to examine the physiological properties of unitary EPSPs.
Abstract: 1. Dual voltage recordings were made from pairs of adjacent, synaptically connected thick tufted layer 5 pyramidal neurones in brain slices of young rat (14-16 days) somatosensory cortex to examine the physiological properties of unitary EPSPs. Pre- and postsynaptic neurones were filled with biocytin and examined in the light and electron microscope to quantify the morphology of axonal and dendritic arbors and the number and location of synaptic contacts on the target neurone. 2. In 138 synaptic connections between pairs of pyramidal neurones 96 (70%) were unidirectional and 42 (30%) were bidirectional. The probability of finding a synaptic connection in dual recordings was 0.1. Unitary EPSPs evoked by a single presynaptic action potential (AP) had a mean peak amplitude ranging from 0.15 to 5.5 mV in different connections with a mean of 1.3 +/- 1.1 mV, a latency of 1.7 +/- 0.9 ms, a 20-80% rise time of 2.9 +/- 2.3 ms and a decay time constant of 40 +/- 18 ms at 32-24 degrees C and -60 +/- 2 mV membrane potential. 3. Peak amplitudes of unitary EPSPs fluctuated randomly from trial to trial. The coefficient of variation (c.v.) of the unitary EPSP amplitudes ranged from 0.13 to 2.8 in different synaptic connections (mean, 0.52; median, 0.41). The percentage of failures of single APs to evoke a unitary EPSP ranged from 0 to 73% (mean, 14%; median, 7%). Both c.v. and percentage of failures decreased with increasing mean EPSP amplitude. 4. Postsynaptic glutamate receptors which mediate unitary EPSPs at -60 mV were predominantly of the L-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptor type. Receptors of the N-methyl-D-aspartate (NMDA) type contributed only a small fraction (< 20%) to the voltage-time integral of the unitary EPSP at -60 mV, but their contribution increased at more positive membrane potentials. 5. Branching patterns of dendrites and axon collaterals of forty-five synaptically connected neurones, when examined in the light microscope, indicated that the axonal and dendritic anatomy of both projecting and target neurones and of uni- and bidirectionally connected neurones was uniform. 6. The number of potential synaptic contacts formed by a presynaptic neurone on a target neurone varied between four and eight (mean, 5.5 +/- 1.1 contacts; n = 19 connections). Synaptic contacts were preferentially located on basal dendrites (63%, 82 +/- 35 microns from the soma, n = 67) and apical oblique dendrites (27%, 145 +/- 59 microns, n = 29), and 35% of all contacts were located on tertiary basal dendritic branches. The mean geometric distances (from the soma) of the contacts of a connection varied between 80 and 585 microns (mean, 147 microns; median, 105 microns). The correlation between EPSP amplitude and the number of morphologically determined synaptic contacts or the mean geometric distances from the soma was only weak (correlation coefficients were 0.2 and 0.26, respectively). 7. Compartmental models constructed from camera lucida drawings of eight target neurones showed that synaptic contacts were located at mean electrotonic distances between 0.07 and 0.33 from the soma (mean, 0.13). Simulations of unitary EPSPs, assuming quantal conductance changes with fast rise time and short duration, indicated that amplitudes of quantal EPSPs at the soma were attenuated, on average, to < 10% of dendritic EPSPs and varied in amplitude up to 10-fold depending on the dendritic location of synaptic contacts. The inferred quantal peak conductance increase varied between 1.5 and 5.5 nS (mean, 3 nS). 8. The combined physiological and morphological measurements in conjunction with EPSP simulations indicated that the 20-fold range in efficacy of the synaptic connections between thick tufted pyramidal neurones, which have their synaptic contacts preferentially located on basal and apical oblique dendrites, was due to differences in transmitter release probability of the projecting neurones and, to a lesser extent, to differenc

973 citations

Journal ArticleDOI
11 Jun 1999-Science
TL;DR: The results suggest that CA1 hippocampal LTP is controlled by the number or subunit composition of AMPA receptors and show a dichotomy between LTP in CA1 and acquisition of spatial memory.
Abstract: Gene-targeted mice lacking the L-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptor subunit GluR-A exhibited normal development, life expectancy, and fine structure of neuronal dendrites and synapses. In hippocampal CA1 pyramidal neurons, GluR-A-/- mice showed a reduction in functional AMPA receptors, with the remaining receptors preferentially targeted to synapses. Thus, the CA1 soma-patch currents were strongly reduced, but glutamatergic synaptic currents were unaltered; and evoked dendritic and spinous Ca2+ transients, Ca2+-dependent gene activation, and hippocampal field potentials were as in the wild type. In adult GluR-A-/- mice, associative long-term potentiation (LTP) was absent in CA3 to CA1 synapses, but spatial learning in the water maze was not impaired. The results suggest that CA1 hippocampal LTP is controlled by the number or subunit composition of AMPA receptors and show a dichotomy between LTP in CA1 and acquisition of spatial memory.

805 citations

Journal ArticleDOI
TL;DR: The results suggest that each connected L4 spiny neurone produces a weak but reliable EPSP in the pyramidal cell, implying that transmission of signals to layer 2/3 is likely to have a high threshold requiring simultaneous activation of many L4 neurons, and postsynaptic glutamate receptors act as a gate for the lateral spread of excitation in layer 1/3.
Abstract: Whole-cell voltage recordings were obtained from 64 synaptically coupled excitatory layer 4 (L4) spiny neurones and L2/3 pyramidal cells in acute slices of the somatosensory cortex ('barrel' cortex) of 17- to 23-days-old rats. Single action potentials (APs) in the L4 spiny neurone evoked single unitary EPSPs in the L2/3 pyramidal cell with a peak amplitude of 0.7 +/- 0.6 mV. The average latency was 2.1 +/- 0.6 ms, the rise time was 0.8 +/- 0.3 ms and the decay time constant was 12.7 +/- 3.5 ms. The percentage of failures of an AP in a L4 spiny neurone to evoke a unitary EPSP in the L2/3 pyramidal cell was 4.9 +/- 8.8 % and the coefficient of variation (c.v.) of the unitary EPSP amplitude was 0.27 +/- 0.13. Both c.v. and percentage of failures decreased with increased average EPSP amplitude. Postsynaptic glutamate receptors (GluRs) in L2/3 pyramidal cells were of the N-methyl-D-aspartate (NMDA) receptor (NMDAR) and the non-NMDAR type. At -60 mV in the presence of extracellular Mg2+ (1 mM), 29 +/- 15 % of the EPSP voltage-time integral was blocked by NMDAR antagonists. In 0 Mg2+, the NMDAR/AMPAR ratio of the EPSC was 0.50 +/- 0.29, about half the value obtained for L4 spiny neurone connections. Burst stimulation of L4 spiny neurones showed that EPSPs in L2/3 pyramidal cells depressed over a wide range of frequencies (1-100 s(-1) ). However, at higher frequencies (30 s(-1)) EPSP summation overcame synaptic depression so that the summed EPSP was larger than the first EPSP amplitude in the train. The number of putative synaptic contacts established by the axonal collaterals of the L4 projection neurone with the target neurone in layer 2/3 varied between 4 and 5, with an average of 4.5 +/- 0.5 (n = 13 pairs). Synapses were established on basal dendrites of the pyramidal cell. Their mean geometric distance from the pyramidal cell soma was 67 +/- 34 microm (range, 16-196 microm). The results suggest that each connected L4 spiny neurone produces a weak but reliable EPSP in the pyramidal cell. Therefore transmission of signals to layer 2/3 is likely to have a high threshold requiring simultaneous activation of many L4 neurons, implying that L4 spiny neurone to L2/3 pyramidal cell synapses act as a gate for the lateral spread of excitation in layer 2/3.

471 citations

Journal ArticleDOI
TL;DR: The results suggest that in L4 of the barrel cortex synaptic transmission between spiny neurones is largely restricted to a single barrel and the connections are very reliable, probably due to a high release probability, and have a high efficacy because of the compact structure of the dendrites and axons of spiny neurons.
Abstract: Dual whole-cell recordings were made from pairs of synaptically coupled excitatory neurones in the ‘barrel field’ in layer (L) 4 in slices of young (postnatal day 12–15) rat somatosensory cortex. The majority of interconnected excitatory neurones were spiny stellate cells with an asymmetrical dendritic arborisation largely confined to a single barrel. The remainder were star pyramidal cells with a prominent apical dendrite terminating in L2/3 without forming a tuft. Excitatory synaptic connections were examined between 131 pairs of spiny L4 neurones. Single presynaptic action potentials evoked unitary EPSPs with a peak amplitude of 1·59 ± 1·51 mV (mean ± s.d.), a latency of 0·92 ± 0·35 ms, a rise time of 1·53 ± 0·46 ms and a decay time constant of 17·8 ± 6·3 ms. At 34–36 °C, the coefficient of variation (c.v.) of the unitary EPSP amplitude was 0·37 ± 0·16 and the percentage of failures to evoke an EPSP was 5·3 ± 7·8%. The c.v. and failure rate decreased with increasing amplitude of the unitary EPSP. Postsynaptic glutamate receptors in spiny L4 neurones were of the AMPA and NMDA type. At −60 mV in the presence of 1 mM Mg2+, NMDA receptors contributed 39·3 ± 12·5% to the EPSP integral. In Mg2+-free solution, the NMDA receptor/AMPA receptor ratio of the EPSC was 0·86 ± 0·64. The number of putative synaptic contacts established by the projection neurone with the target neurone varied between two and five with a mean of 3·4 ± 1·0 (n = 11). Synaptic contacts were exclusively found in the barrel in which the cell pair was located and were preferentially located on secondary to quarternary dendritic branches. Their mean geometric distance from the soma was 68·8 ± 37·4 μm (range, 33·4-168·0 μm). The number of synaptic contacts and mean EPSP amplitude showed no significant correlation. The results suggest that in L4 of the barrel cortex synaptic transmission between spiny neurones is largely restricted to a single barrel. The connections are very reliable, probably due to a high release probability, and have a high efficacy because of the compact structure of the dendrites and axons of spiny neurones. Intrabarrel connections thus function to amplify and distribute the afferent thalamic activity in the vertical directions of a cortical column. In rodents, whisker-related patterns of neuronal architecture are present at the level of the brainstem trigeminal nuclei, the ventrobasal thalamus and the somatosensory cortex. In 1970, Woolsey & van der Loos described neuronal clusters in layer (L) 4 of the mouse somatosensory cortex that mirror the topography of the whisker pad on the animal's muzzle. These cell clusters were named ‘barrels’ and it is now established that each cortical barrel represents a principal whisker on the contralateral side of the face in a one-to-one relationship (Woolsey & van der Loos, 1970; Welker, 1976; Wallace, 1987; Agmon & Connors, 1991; for a review see Jones & Diamond, 1995). The columnar organisation and receptive field properties of these neurones appear to be comparatively simple. This should facilitate elucidation of cortical signal flow at the cellular level. Afferent nerve fibres from the thalamic ‘relay nuclei’ terminate in L4 of the sensory cortices (Hubel & Wiesel, 1962; Killackey, 1973; Jensen & Killackey, 1987; Lu & Lin, 1993; for reviews see Ebner & Armstrong-James, 1990; Jones & Diamond, 1995). The primary targets of thalamic afferents are excitatory spiny neurones, the majority being spiny stellate cells while a smaller fraction appears to be made up of star pyramidal cells (Lund, 1984; Ahmed et al. 1994; Hirsch, 1995; Stratford et al. 1996). The first step of intracortical signal processing takes place between synaptically coupled spiny neurones in L4; from there, information is relayed to supragranular laminae (Armstrong-James et al. 1992). The main aim of the present study was to investigate the physiological and morphological factors responsible for fast excitatory synaptic transmission within L4 of the barrel cortex. We used dual whole-cell voltage recordings and morphological reconstruction of biocytin-filled spiny neurones to determine the functional properties of EPSPs and the number and dendritic location of synaptic contacts. The results suggest that synapses of spiny L4 neurones are functionally different from other neocortical synapses (Thomson & West, 1993; Thomson et al. 1996; Markram et al. 1997; for a review see Thomson & Deuchars, 1997). Connected neurones were confined to a single barrel and synaptic contacts were established exclusively within the barrel. In comparison to other cortical connections, unitary EPSPs had a low variability and failure rate and, on occasion, were sufficiently large to evoke action potentials (APs) in the target neurone. These properties render synaptically connected spiny stellate and star pyramidal neurones of the barrel cortex well suited to amplify and subsequently distribute incoming thalamic signals within the cortical column. Preliminary data from this study have been presented in abstract form (Feldmeyer & Egger, 1998).

435 citations


Cited by
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Book
01 Jan 1988
TL;DR: This book provides a clear and simple account of the key ideas and algorithms of reinforcement learning, which ranges from the history of the field's intellectual foundations to the most recent developments and applications.
Abstract: Reinforcement learning, one of the most active research areas in artificial intelligence, is a computational approach to learning whereby an agent tries to maximize the total amount of reward it receives when interacting with a complex, uncertain environment. In Reinforcement Learning, Richard Sutton and Andrew Barto provide a clear and simple account of the key ideas and algorithms of reinforcement learning. Their discussion ranges from the history of the field's intellectual foundations to the most recent developments and applications. The only necessary mathematical background is familiarity with elementary concepts of probability. The book is divided into three parts. Part I defines the reinforcement learning problem in terms of Markov decision processes. Part II provides basic solution methods: dynamic programming, Monte Carlo methods, and temporal-difference learning. Part III presents a unified view of the solution methods and incorporates artificial neural networks, eligibility traces, and planning; the two final chapters present case studies and consider the future of reinforcement learning.

37,989 citations

28 Jul 2005
TL;DR: PfPMP1)与感染红细胞、树突状组胞以及胎盘的单个或多个受体作用,在黏附及免疫逃避中起关键的作�ly.
Abstract: 抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1(PfPMP1)与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用,在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员,通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

18,940 citations

Journal ArticleDOI
TL;DR: The results underscore the importance of precise spike timing, synaptic strength, and postsynaptic cell type in the activity-induced modification of central synapses and suggest that Hebb’s rule may need to incorporate a quantitative consideration of spike timing that reflects the narrow and asymmetric window for the induction of synaptic modification.
Abstract: In cultures of dissociated rat hippocampal neurons, persistent potentiation and depression of glutamatergic synapses were induced by correlated spiking of presynaptic and postsynaptic neurons. The relative timing between the presynaptic and postsynaptic spiking determined the direction and the extent of synaptic changes. Repetitive postsynaptic spiking within a time window of 20 msec after presynaptic activation resulted in long-term potentiation (LTP), whereas postsynaptic spiking within a window of 20 msec before the repetitive presynaptic activation led to long-term depression (LTD). Significant LTP occurred only at synapses with relatively low initial strength, whereas the extent of LTD did not show obvious dependence on the initial synaptic strength. Both LTP and LTD depended on the activation of NMDA receptors and were absent in cases in which the postsynaptic neurons were GABAergic in nature. Blockade of L-type calcium channels with nimodipine abolished the induction of LTD and reduced the extent of LTP. These results underscore the importance of precise spike timing, synaptic strength, and postsynaptic cell type in the activity-induced modification of central synapses and suggest that Hebb’s rule may need to incorporate a quantitative consideration of spike timing that reflects the narrow and asymmetric window for the induction of synaptic modification.

4,382 citations

Journal Article
TL;DR: The cloning of cDNAs encoding glutamate receptor subunits, which occurred mainly between 1989 and 1992, stimulated the development of ionotropic glutamate receptors in the brain.
Abstract: The ionotropic glutamate receptors are ligand-gated ion channels that mediate the vast majority of excitatory neurotransmission in the brain. The cloning of cDNAs encoding glutamate receptor subunits, which occurred mainly between 1989 and 1992 ([Hollmann and Heinemann, 1994][1]), stimulated this

4,112 citations

Journal ArticleDOI
30 Sep 2004-Neuron
TL;DR: This work reviews those forms of LTP and LTD for which mechanisms have been most firmly established and examples are provided that show how these mechanisms can contribute to experience-dependent modifications of brain function.

3,767 citations