Increased excitatory synaptic activity and local connectivity of hippocampal CA1 pyramidal cells in rats with kainate-induced epilepsy.
AuthorsShao LR, Dudek FE
JournalJ Neurophysiol
PubMed ID15084640
'Formation of local excitatory circuits may contribute to epileptogenesis. We tested the hypothesis that epileptogenesis is associated with increased recurrent excitation in the hippocampal CA1 area of rats with kainate-induced epilepsy. Whole cell recordings were obtained during focal flash photolysis of caged glutamate, which served as a focal excitant to ... More
Excitatory synaptic input to granule cells increases with time after kainate treatment.
AuthorsWuarin JP, Dudek FE
JournalJ Neurophysiol
PubMed ID11247977
'Temporal lobe epilepsy is usually associated with a latent period and an increased seizure frequency following a precipitating insult. After kainate treatment, the mossy fibers of the dentate gyrus are hypothesized to form recurrent excitatory circuits between granule cells, thus leading to a progressive increase in the excitatory input to ... More
Early intermediates in the transport cycle of the neuronal excitatory amino acid carrier EAAC1.
AuthorsWatzke N, Bamberg E, Grewer C
JournalJ Gen Physiol
PubMed ID11382805
'Electrogenic glutamate transport by the excitatory amino acid carrier 1 (EAAC1) is associated with multiple charge movements across the membrane that take place on time scales ranging from microseconds to milliseconds. The molecular nature of these charge movements is poorly understood at present and, therefore, was studied in this report ... More
Selective enhancement of synaptic inhibition by hypocretin (orexin) in rat vagal motor neurons: implications for autonomic regulation.
AuthorsDavis SF, Williams KW, Xu W, Glatzer NR, Smith BN
JournalJ Neurosci
PubMed ID12736355
'The hypocretins (orexins) are hypothalamic neuropeptides implicated in feeding, arousal, and autonomic regulation. These studies were designed to determine the actions of hypocretin peptides on synaptic transmission in the dorsal motor nucleus of the vagus nerve (DMV). Whole-cell patch-clamp recordings were made from DMV neurons in transverse slices of rat ... More
How fast does the GluR1Qflip channel open?
AuthorsLi G, Niu L
JournalJ Biol Chem
PubMed ID14610080
'Opening of a ligand-gated ion channel is the step at which the binding of a neurotransmitter is transduced into the electrical signal by allowing ions to flow through the transmembrane channel, thereby altering the postsynaptic membrane potential. We report the kinetics for the opening of the GluR1Qflip channel, an alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic ... More
Focal photolysis of caged glutamate produces long-term depression of hippocampal glutamate receptors.
AuthorsKandler K, Katz LC, Kauer JA
JournalNat Neurosci
PubMed ID10195126
'Separating contributions of pre- and postsynaptic factors to the maintenance of long-term potentiation (LTP) and long-term depression (LTD) has been confounded by their experimental interdependence. To isolate the postsynaptic contribution, glutamate-receptor-mediated currents were elicited by localized photolysis of caged glutamate in small spots along the dendrites of CA1 hippocampal pyramidal ... More
Neocortical long-term potentiation and long-term depression: site of expression investigated by infrared-guided laser stimulation.
AuthorsEder M, Zieglgänsberger W, Dodt HU
JournalJ Neurosci
PubMed ID12196579
'The synaptic site of expression of long-term potentiation (LTP) and long-term depression (LTD) is still a matter of debate. To address the question of presynaptic versus postsynaptic expression of neocortical LTP and LTD in a direct approach, we measured the glutamate sensitivity of apical dendrites of layer 5 pyramidal neurons ... More
Channel-opening kinetics of GluR6 kainate receptor.
AuthorsLi G, Oswald RE, Niu L
JournalBiochemistry
PubMed ID14567698
'GluR6 is an ionotropic glutamate receptor subunit of the kainate subtype. It plays an essential role in synaptic plasticity and epilepsy. We expressed this recombinant receptor in HEK-293 cells and characterized the glutamate-induced channel-opening reaction, using a laser-pulse photolysis technique with the caged glutamate (gamma-O-(alpha-carboxy-2-nitrobenzyl)glutamate). This technique permits glutamate to ... More
Topographic specificity of functional connections from hippocampal CA3 to CA1.
AuthorsBrivanlou IH, Dantzker JL, Stevens CF, Callaway EM
JournalProc Natl Acad Sci U S A
PubMed ID14983048
'The hippocampus is a cortical region thought to play an important role in learning and memory. Most of our knowledge about the detailed organization of hippocampal circuitry responsible for these functions is derived from anatomical studies. These studies present an incomplete picture, however, because the functional character and importance of ... More
Photolysis of gamma-(alpha-carboxy-2-nitrobenzyl)-L-glutamic acid investigated in the mcrosecond time scale by time-resolved FTIR.
AuthorsCheng Q, Steinmetz MG, Jayaraman V
JournalJ Am Chem Soc
PubMed ID12083919
'The photolytic release of substrates from caged substrates has proven to be an excellent method to generate concentration jumps for kinetic measurements in the microsecond time scale. In this report we use time-resolved FTIR in the step-scan mode to probe the photolysis mechanism of one such caged compound, namely gamma-(alpha-carboxy-2-nitrobenzyl)glutamate, ... More
Precisely localized LTD in the neocortex revealed by infrared-guided laser stimulation.
AuthorsDodt H, Eder M, Frick A, Zieglgänsberger W
JournalScience
PubMed ID10506556
'In a direct approach to elucidate the origin of long-term depression (LTD), glutamate was applied onto dendrites of neurons in rat neocortical slices. An infrared-guided laser stimulation was used to release glutamate from caged glutamate in the focal spot of an ultraviolet laser. A burst of light flashes caused an ... More
Optical release of caged glutamate for stimulation of neurons in the in vitro slice preparation.
'Optical stimulation techniques prove useful to map functional inputs in the in vitro brain slice preparation: Glutamate released by a focused beam of UV light induces action potentials, which can be detected in postsynaptic neurons. The direct activation effect is influenced by factors such as compound concentration, focus depth, light ... More
Layer-specific intracolumnar and transcolumnar functional connectivity of layer V pyramidal cells in rat barrel cortex.
AuthorsSchubert D, Staiger JF, Cho N, Kötter R, Zilles K, Luhmann HJ
JournalJ Neurosci
PubMed ID11331387
'Layer V pyramidal cells in rat barrel cortex are considered to play an important role in intracolumnar and transcolumnar signal processing. However, the precise circuitry mediating this processing is still incompletely understood. Here we obtained detailed maps of excitatory and inhibitory synaptic inputs onto the two major layer V pyramidal ... More
Compartmentalized and binary behavior of terminal dendrites in hippocampal pyramidal neurons.
AuthorsWei DS, Mei YA, Bagal A, Kao JP, Thompson SM, Tang CM
JournalScience
PubMed ID11567143
'The dendritic arbor of pyramidal neurons is not a monolithic structure. We show here that the excitability of terminal apical dendrites differs from that of the apical trunk. In response to fluorescence-guided focal photolysis of caged glutamate, individual terminal apical dendrites generated cadmium-sensitive all-or-none responses that were subthreshold for somatic ... More
Postsynaptic modulation of AMPA- and NMDA-receptor currents by Group III metabotropic glutamate receptors in rat nucleus accumbens.
AuthorsTaverna S, Pennartz CM
JournalBrain Res
PubMed ID12763622
'Whole cell patch clamp recordings from rat nucleus accumbens neurons were made in order to study the effect of metabotropic glutamate receptors and dopamine on postsynaptic glutamate receptor mediated currents. AMPA- and NMDA-R currents were evoked by flash photolysis of caged glutamate, while spike-dependent release of neurotransmitters was prevented by ... More
Identity of a pathway for saccadic suppression.
AuthorsLee PH, Sooksawate T, Yanagawa Y, Isa K, Isa T, Hall WC
JournalProc Natl Acad Sci U S A
PubMed ID17420449
'Neurons in the superficial gray layer (SGS) of the superior colliculus receive visual input and excite intermediate layer (SGI) neurons that play a critical role in initiating rapid orienting movements of the eyes, called saccades. In the present study, two types of experiments demonstrate that a population of SGI neurons ... More
Inhibition of backpropagating action potentials in mitral cell secondary dendrites.
AuthorsLowe G
JournalJ Neurophysiol
PubMed ID12091533
'The mammalian olfactory bulb is a geometrically organized signal-processing array that utilizes lateral inhibitory circuits to transform spatially patterned inputs. A major part of the lateral circuitry consists of extensively radiating secondary dendrites of mitral cells. These dendrites are bidirectional cables: they convey granule cell inhibitory input to the mitral ... More
Identification of chemical synapses in the pharynx of Caenorhabditis elegans.
AuthorsLi H, Avery L, Denk W, Hess GP
JournalProc Natl Acad Sci U S A
PubMed ID9159174
'The rhythmic contraction of the Caenorhabditis elegans pharynx is unique in that the network of 12 neurons, including two M3 neurons, that regulate the contraction is known. The neurotransmitters secreted by these cells, and the target cells responding to these chemical signals, are not known. Here, we describe an approach ... More
Fourier transform infrared spectroscopic characterization of a photolabile precursor of glutamate.
AuthorsJayaraman V, Thiran S, Madden DR
JournalFEBS Lett
PubMed ID10869571
'Recently, it has been demonstrated that Fourier transform infrared spectroscopy (FTIR) detects conformational changes in the glutamate receptor ligand-binding domain that are associated with agonist binding. Combined with flash photolysis, this observation offers the prospect of following conformational changes at individual protein and agonist moieties in parallel and with high ... More
Development and application of caged ligands for neurotransmitter receptors in transient kinetic and neuronal circuit mapping studies.
AuthorsHess GP, Grewer C
JournalMethods Enzymol
PubMed ID9661164
Confocal microscopic imaging of fast UV-laser photolysis of caged compounds.
AuthorsKorkotian E, Oron D, Silberberg Y, Segal M
JournalJ Neurosci Methods
PubMed ID14757356
Using a pulsed UV laser in a confocal scanning microscope, we present a relatively cheap, accurate and efficient method for fast UV laser flash photolysis of caged molecules in two-dimensional cultured neurons. The laser light is introduced through the imaging optics, can be localized by a parallel red laser and ... More
Caged compounds: photorelease technology for control of cellular chemistry and physiology.
AuthorsEllis-Davies GC
JournalNat Methods
PubMed ID17664946
Caged compounds are light-sensitive probes that functionally encapsulate biomolecules in an inactive form. Irradiation liberates the trapped molecule, permitting targeted perturbation of a biological process. Uncaging technology and fluorescence microscopy are 'optically orthogonal': the former allows control, and the latter, observation of cellular function. Used in conjunction with other technologies ... More
Stimulating neurons with light.
AuthorsCallaway EM, Yuste R
JournalCurr Opin Neurobiol
PubMed ID12367640
Recent technological advances have enabled the use of different optical methods to activate neurons, including 'caged' glutamate, photoactivation of genetically engineered cascades, and direct two-photon excitation. The ability to use light as a stimulation tool provides, in principle, a non-invasive method for the temporally and spatially precise activation of any ... More
NMDA and AMPA receptors on neocortical neurons are differentially distributed.
AuthorsDodt HU, Frick A, Kampe K, Zieglgänsberger W
JournalEur J Neurosci
PubMed ID9824448
The distribution of glutamate receptor subtypes on the surface of neurons is highly relevant for synaptic activation and signal processing in the neocortex. As a novel approach we have used infra-red videomicroscopy in combination with photostimulation or microiontophoresis in brain slices of rat neocortex to map the distribution of N-methyl-D-aspartate ... More
Temporal integration can readily switch between sublinear and supralinear summation.
AuthorsMargulis M, Tang CM
JournalJ Neurophysiol
PubMed ID9582247
Temporal summation at dendrites of cultured rat hippocampal neurons was examined as a function of the interval separating two dendritic inputs. A novel method that relies on single-mode optical fibers to achieve rapid photorelease of glutamate was developed. Dendritic excitation achieved with this approach resembles that associated with miniature excitatory ... More
Restricted photorelease of biologically active molecules near the plasma membrane.
AuthorsSuga T, Hirano M, Takayanagi M, Koshimoto H, Watanabe A
JournalBiochem Biophys Res Commun
PubMed ID9878552
An evanescent wave of ultraviolet light was successfully used to release biologically active molecules from caged compounds in living cells. The evanescent wave was generated by the total internal reflection in a limited region near the plasma membrane attached to the illuminated interface. At first, the photolysis efficiency of the ... More
Quantification of spread of cerebellar long-term depression with chemical two-photon uncaging of glutamate.
AuthorsWang SS, Khiroug L, Augustine GJ
JournalProc Natl Acad Sci U S A
PubMed ID10890882
Localized, chemical two-photon photolysis of caged glutamate was used to map the changes in alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-type glutamate receptors caused by long-term synaptic depression (LTD) in cerebellar Purkinje cells. LTD produced by pairing parallel fiber activity with depolarization was accompanied by a decline in the response of Purkinje cells to uncaged ... More
Cell type-specific circuits of cortical layer IV spiny neurons.
Sensory signal processing in cortical layer IV involves two major morphological classes of excitatory neurons: spiny stellate and pyramidal cells. It is essentially unknown how these two cell types are integrated into intracortical networks and whether they play different roles in cortical signal processing. We mapped their cell-specific intracortical afferents ... More
Circuitry of rat barrel cortex investigated by infrared-guided laser stimulation.
AuthorsDodt HU, Schierloh A, Eder M, Zieglgänsberger W
JournalNeuroreport
PubMed ID12657899
Infrared-guided laser stimulation was used to examine the synaptic connectivity of neurons in rat barrel cortex. Layer V pyramidal neurons were visualized by infrared videomicroscopy and their membrane potential was recorded with patch pipettes. Presumptive presynaptic neurons were activated by uncaging glutamate with the light of a uv laser directed ... More
Convergence of magno- and parvocellular pathways in layer 4B of macaque primary visual cortex.
AuthorsSawatari A, Callaway EM
JournalNature
PubMed ID8602243
Early visual processing is characterized by two independent parallel pathways: the magnocellular stream, which carries information useful for motion analysis, and the parvocellular stream, which carries information useful for analyses of shape and colour. Although increasing anatomical and physiological evidence indicates some degree of convergence of the two streams, the ... More
Mechanism and kinetics of heterosynaptic depression at a cerebellar synapse.
AuthorsDittman JS, Regehr WG
JournalJ Neurosci
PubMed ID9364051
High levels of activity at a synapse can lead to spillover of neurotransmitter from the synaptic cleft. This extrasynaptic neurotransmitter can diffuse to neighboring synapses and modulate transmission via presynaptic receptors. We studied such modulation at the synapse between granule cells and Purkinje cells in rat cerebellar slices. Brief tetanic ... More
Photolabile precursors of glutamate: synthesis, photochemical properties, and activation of glutamate receptors on a microsecond time scale.
Newly synthesized photolabile derivatives of glutamate, caged glutamate, that release free glutamate on a microsecond time scale after a pulse of UV laser light are described. 2-Nitrobenzyl derivatives were attached to the amino or carboxyl groups of glutamate. Substitution with a -CO2- group at the benzylic carbon accelerates the photolysis ... More
Morphology, electrophysiology and functional input connectivity of pyramidal neurons characterizes a genuine layer va in the primary somatosensory cortex.
Cortical layer V classically has been subdivided into sublayers Va and Vb on cytoarchitectonic grounds. In the analysis of cortical microcircuits, however, layer Va has largely been ignored. The purpose of this study was to investigate pyramidal neurons of layer Va in view of their potential role in integrating information ... More
Analysing functional connectivity in brain slices by a combination of infrared video microscopy, flash photolysis of caged compounds and scanning methods.
AuthorsKötter R, Staiger JF, Zilles K, Luhmann HJ
JournalNeuroscience
PubMed ID9692760
We evaluate a novel set-up for scanning functional connectivity in brain slices from the somatosensory cortex of the rat. Upright infrared video microscopy for targeted placement of electrodes is combined with rapid photolysis of bath-applied caged neurotransmitter induced by a xenon flash lamp. Flash photolysis of caged glutamate and electrical ... More
Photostimulation with caged neurotransmitters using fiber optic lightguides.
AuthorsGodwin DW, Che D, O'Malley DM, Zhou Q
JournalJ Neurosci Methods
PubMed ID9130682
'Caged' neurotransmitters are molecules that are transformed to a neuroactive state by exposure to light of an appropriate wavelength and intensity. Use of these substances has centered on in vitro bath application and subsequent activation using light from lasers or flashlamps that is delivered into the preparation through microscope optics. ... More
Isolation of glutamate transport-coupled charge flux and estimation of glutamate uptake at the climbing fiber-Purkinje cell synapse.
AuthorsBrasnjo G, Otis TS
JournalProc Natl Acad Sci U S A
PubMed ID15067125
Excitatory amino acid transporters (EAATs) located on neurons and glia are responsible for limiting extracellular glutamate concentrations, but specific contributions made by neuronal and glial EAATs have not been determined. At climbing fiber to Purkinje cell (PC) synapses in cerebellum, a fraction of released glutamate is rapidly bound and inactivated ... More
Glutamate receptors form hot spots on apical dendrites of neocortical pyramidal neurons.
AuthorsFrick A, Zieglgänsberger W, Dodt HU
JournalJ Neurophysiol
PubMed ID11535687
Apical dendrites of layer V cortical pyramidal neurons are a major target for glutamatergic synaptic inputs from cortical and subcortical brain regions. Because innervation from these regions is somewhat laminar along the dendrites, knowing the distribution of glutamate receptors on the apical dendrites is of prime importance for understanding the ... More
Mossy fiber-granule cell synapses in the normal and epileptic rat dentate gyrus studied with minimal laser photostimulation.
AuthorsMolnár P, Nadler JV
JournalJ Neurophysiol
PubMed ID10515977
Dentate granule cells become synaptically interconnected in the hippocampus of persons with temporal lobe epilepsy, forming a recurrent mossy fiber pathway. This pathway may contribute to the development and propagation of seizures. The physiology of mossy fiber-granule cell synapses is difficult to characterize unambiguously, because electrical stimulation may activate other ... More
Organization of the intermediate gray layer of the superior colliculus. I. Intrinsic vertical connections.
AuthorsHelms MC, Ozen G, Hall WC
JournalJ Neurophysiol
PubMed ID15010497
A pathway from the superficial visual layers to the intermediate premotor layers of the superior colliculus has been proposed to mediate visually guided orienting movements. In these experiments, we combined photostimulation using "caged" glutamate with in vitro whole cell patch-clamp recording to demonstrate this pathway in the rat. Photostimulation in ... More
Laminar characteristics of functional connectivity in rat barrel cortex revealed by stimulation with caged-glutamate.
AuthorsStaiger JF, Kötter R, Zilles K, Luhmann HJ
JournalNeurosci Res
PubMed ID10802343
In rodent somatosensory (barrel) cortex input is processed by whisker-related columns before the integrated output is fed into behaviorally-relevant circuits. The layer-specific activation patterns of the rat barrel cortex were examined with a set-up for scanning functional connectivity in brain slices. Flash-induced release of caged-glutamate at a large number of ... More
Glutamate translocation of the neuronal glutamate transporter EAAC1 occurs within milliseconds.
AuthorsGrewer C, Watzke N, Wiessner M, Rauen T
JournalProc Natl Acad Sci U S A
PubMed ID10931942
The activity of glutamate transporters is essential for the temporal and spatial regulation of the neurotransmitter concentration in the synaptic cleft, and thus, is crucial for proper excitatory signaling. Initial steps in the process of glutamate transport take place within a time scale of microseconds to milliseconds. Here we compare ... More
Is the glutamate residue Glu-373 the proton acceptor of the excitatory amino acid carrier 1?
AuthorsGrewer C, Watzke N, Rauen T, Bicho A
JournalJ Biol Chem
PubMed ID12419818
Glutamate transport by the neuronal excitatory amino acid carrier (EAAC1) is accompanied by the coupled movement of one proton across the membrane. We have demonstrated previously that the cotransported proton binds to the carrier in the absence of glutamate and, thus, modulates the EAAC1 affinity for glutamate. Here, we used ... More