@article{2622, abstract = {To understand the possible contribution of metabotropic γ-aminobutyric acid receptors (GABABR) in cortical development, we investigated the expression pattern and the cellular and subcellular localization of the GABABR1 and GABABR2 subtypes in the rat neocortex from embryonic day 14 (E14) to adulthood. At the light microscopic level, both GABABR1 and GABABR2 were detected as early as E14. During prenatal development, both subtypes were expressed highly in the cortical plate. Using double immunofluorescence, GABABR1 colocalized with GABABR2 in neurons of the marginal zone and subplate, indicating that these proteins are coexpressed and could be forming functional GABABRs during prenatal development in vivo. In contrast, only GABABR1 but not GABABR2 was detected in the tangentially migratory cells in the lower intermediate zone. During postnatal development, immunoreactivity for GABABR1 and GABABR2 was distributed mainly in pyramidal cells. Discrete GABABR1-immunopositive cell bodies of interneurons were present throughout the neocortex. In addition, GABABR1 but not GABABR2 was found in identified Cajal-Retzius cells in layer I. At the electron microscopic level, immunoreactivity for GABABR1 and GABABR2 was found in dendritic spines and dendritic shafts at extrasynaptic and perisynaptic sites throughout postnatal development. We further demonstrated the presynaptic localization of GABABR1 and GABABR2, as well as the association of the receptors with asymmetrical synaptic junctions. These results indicate potentially important roles for the GABABRs in the regulation of migratory processes during corticogenesis and in the modulation of synaptic transmission during early development of cortical circuitry.}, author = {López Bendito, Guillermina and Shigemoto, Ryuichi and Kulik, Ákos and Paulsen, Ole and Fairén, Alfonso and Luján, Rafael}, issn = {0953-816X}, journal = {European Journal of Neuroscience}, number = {11}, pages = {1766 -- 1778}, publisher = {Wiley-Blackwell}, title = {{Expression and distribution of metabotropic GABA receptor subtypes GABABR1 and GABABR2 during rat neocortical development}}, doi = {10.1046/j.1460-9568.2002.02032.x}, volume = {15}, year = {2002}, } @article{2624, abstract = {Metabotropic γ-aminobutyric acid receptors (GABABRs) are involved in modulation of synaptic transmission and activity of cerebellar and thalamic neurons. We used subtype-specific antibodies in pre- and postembedding immunohistochemistry combined with three-dimensional reconstruction of labelled profiles and quantification of immunoparticles to reveal the subcellular distribution of pre- and postsynaptic GABABR1a/b and GABABR2 in the rat cerebellum and ventrobasal thalamus. GABABR1a/b and R2 were extensively colocalized in most brain regions including the cerebellum and thalamus. In the cerebellum, immunoreactivity for both subtypes was prevalent in the molecular layer. The most intense immunoreactivity was found in Purkinje cell spines with a high density of immunoparticles at extrasynaptic sites peaking at around 240 nm from glutamatergic synapses between spines and parallel fibre varicosities. This is in contrast to dendrites at sites around GABAergic synapses where sparse and random distribution was found for both subtypes. In addition, more than one-tenth of the synaptic membrane specialization of spine-parallel fibre synapses were labelled at pre- or postsynaptic sites. Weak immunolabelling for both subtypes was also seen in parallel fibres but only rarely in GABAergic axons. In the ventrobasal thalamus, immunolabelling for both receptor subtypes was intense over the dendritic field of thalamocortical cells. Electron microscopy demonstrated an extrasynaptic localization of GABABR1a/b and R2 exclusively in postsynaptic elements. Quantitative analysis further revealed the density of GABABR1a/b around GABAergic synapses was higher than glutamatergic synapses on thalamocortical cell dendrites. The distinct localization of GABABRs relative to synaptic sites in the cerebellum and ventrobasal thalamus suggests that GABABRs differentially regulate activity of different neuronal populations.}, author = {Kulik, Ákos and Nakadate, Kazuhiko and Nyíri, Gábor and Notomi, Takuya and Malitschek, Barbara and Bettler, Bernhard and Shigemoto, Ryuichi}, issn = {0953-816X}, journal = {European Journal of Neuroscience}, number = {2}, pages = {291 -- 307}, publisher = {Wiley-Blackwell}, title = {{Distinct localization of GABAB receptors relative to synaptic sites in the rat cerebellum and ventrobasal thalamus}}, doi = {10.1046/j.0953-816x.2001.01855.x}, volume = {15}, year = {2002}, } @article{2606, abstract = {Glutamate receptors have been linked to the regulation of several developmental events in the CNS. By using cortical slices of early postnatal mice, we show that in layer I cells, glutamate produces intracellular calcium ([Ca2+]i) elevations mediated by ionotropic and metabotropic glutamate receptors (mGluRs). The contribution of mGluRs to these responses was demonstrated by application of tACPD, an agonist to groups I and II mGluRs, which evoked [Ca2+]i increases that could be reversibly blocked by MCPG, an antagonist to groups I and II mGluRs. In the absence of extracellular Ca2+, repetitive applications of tACPD or quisqualate, an agonist to group I mGluRs, elicited decreasing [Ca2+]i responses that were restored by refilling a thapsigargin-sensitive Ca2+ store. The use of specific group I mGluR agonists CHPG and DHPG indicated that the functional mGluR in layer I was of the mGluR1 subtype. Subtype specific antibodies confirmed the presence of mGlur1α, but not mGluR5, in Cajal-Retzius (Reelin-immunoreactive) neurons.}, author = {Martínez, Galán and López Bendito, Guillermina and Luján, Rafael and Shigemoto, Ryuichi and Fairén, Alfonso and Valdeolmillos, Miguel}, issn = {0953-816X}, journal = {European Journal of Neuroscience}, number = {6}, pages = {1147 -- 1154}, publisher = {Wiley-Blackwell}, title = {{Cajal-Retzius cells in early postnatal mouse cortex selectively express functional metabotropic glutamate receptors}}, doi = {10.1046/j.0953-816X.2001.01494.x}, volume = {13}, year = {2001}, } @article{3519, abstract = {In contrast to sensory cortical areas of the brain, the relevant physiological inputs to the hippocampus, leading to selective activation of pyramidal cells, are largely unknown. Pyramidal cells are thought to be phasically activated by spatial cues and a variety of sensory and motor stimuli. Here, we used a behavioural `space clamp' method, which involved the confinement of the actively running animal in a defined position in space (running wheel) and kept sensory inputs constant. Twelve percent of the recorded CA1 pyramidal cells were selectively active while the rat was running in the wheel. Cell firing was specific to the direction of running and disappeared after rotating the recording apparatus. The discharge frequency of pyramidal cells and interneurons was sustained as long as the rat ran continuously in the wheel. Furthermore, the discharge frequency of pyramidal cells and interneurons increased with increasing running velocity, even though the frequency of hippocampal theta waves remained constant. The discharge frequency of some `wheel-related' pyramidal cells could increase more than 10-fold between 10 and 100 cm/s, whereas the firing rate of `non-wheel' cells remained constantly low. We hypothesize that: (i) a necessary condition for place-specific discharge of hippocampal pyramidal cells is the presence of theta oscillation; and (ii) relevant stimuli can tonically and selectively activate hippocampal pyramidal cells as long as theta activity is present.}, author = {Czurkó, András and Hirase, Hajima and Csicsvari, Jozsef L and Buzsáki, György}, issn = {0953-816X}, journal = {European Journal of Neuroscience}, number = {1}, pages = {344 -- 352}, publisher = {Wiley-Blackwell}, title = {{Sustained activation of hippocampal pyramidal cells by ‘space clamping' in a running wheel}}, doi = {10.1046/j.1460-9568.1999.00446.x}, volume = {11}, year = {1999}, } @article{3539, abstract = {In the hippocampus, spatial representation of the environment has been suggested to be coded by either the firing rate of pyramidal cell assemblies or the relative timing of the action potentials during the theta EEG cycle. Here, we used a behavioural `space clamp' method, which involved the confinement of the actively running animal in a defined position in space (running wheel) to examine how `spatial' and other inputs affect firing rate and timing of hippocampal CA1 pyramidal cells and interneurons. Nineteen per cent of the recorded CA1 pyramidal cells were selectively active while the rat was running in the wheel in a given direction ('wheel' cells). Spatial rotation of the apparatus showed that selective discharge of pyramidal cells in the wheel was under the combined influence of distal and apparatus cues. During steady running, both discharge rate and theta phase were constant. Rotation of the wheel apparatus resulted in a shift of both firing rate and preferred theta phase. The discharge frequency of `wheel' cells increased threefold (on average) with increasing running velocity. In contrast, change in running speed had relatively little effect on the theta phase-related discharge of `wheel' cells. Our findings indicate that mechanisms that regulate rate and phase of spikes are overlapping but not necessarily identical.}, author = {Hirase, Hajima and Czurkó, András and Csicsvari, Jozsef L and Buzsáki, György}, issn = {0953-816X}, journal = {European Journal of Neuroscience}, number = {12}, pages = {4373 -- 4380}, publisher = {Wiley-Blackwell}, title = {{Firing rate and theta-phase coding by hippocampal pyramidal neurons during ‘space clamping’}}, doi = {10.1046/j.1460-9568.1999.00853.x}, volume = {11}, year = {1999}, } @article{2574, abstract = {lonotropic and metabotropic (mGluR1a) glutamate receptors were reported to be segregated from each other within the postsynaptic membrane at individual synapses. In order to establish whether this pattern of distribution applies to the hippocampal principal cells and to other postsynaptic metabotropic glutamate receptors, the mGluR1a/b/c and mGluR5 subtypes were localized by immunocytochemistry. Principal cells in all hippocampal fields were reactive for mGluR5, the strata oriens and radiatum of the CA1 area being most strongly immunolabelled. Labelling for mGluR1b/c was strongest on some pyramids in the CA3 area, weaker on granule cells and absent on CA1 pyramids. Subpopulations of non-principal cells showed strong mGluR1 or mGluR5 immunoreactivity. Electron microscopic pre-embedding immunoperoxidase and both pre- and postembedding immunogold methods consistently revealed the extrasynaptic location of both mGluRs in the somatic and dendritic membrane of pyramidal and granule cells. The density of immunolabelling was highest on dendritic spines. At synapses, immunoparticles for both mGluR1 and mGluR5 were found always outside the postsynaptic membrane specializations. Receptors were particularly concentrated in a perisynaptic annulus around type 1 synaptic junctions, including the invaginations at 'perforated' synapses. Measurements of immunolabelling on dendritic spines showed decreasing levels of receptor as a function of distance from the edge of the synaptic specialization. We propose that glutamatergic synapses with an irregular edge develop in order to increase the circumference of synaptic junctions leading to an increase in the metabotropic to ionotropic glutamate receptor ratio at glutamate release sites. The perisynaptic position of postsynaptic metabotropic glutamate receptors appears to be a general feature of glutamatergic synaptic organization and may apply to other G-protein-coupled receptors. © European Neuroscience Association.}, author = {Luján, Rafael and Nusser, Zoltán and Roberts, John and Shigemoto, Ryuichi and Somogyi, Péter}, issn = {0953-816X}, journal = {European Journal of Neuroscience}, number = {7}, pages = {1488 -- 1500}, publisher = {Wiley-Blackwell}, title = {{ Perisynaptic location of metabotropic glutamate receptors mGluR1 and mGluR5 on dendrites and dendritic spines in the rat hippocampus}}, doi = {10.1111/j.1460-9568.1996.tb01611.x}, volume = {8}, year = {1996}, } @article{4175, abstract = {We have studied the effects of different neurotrophins on the survival and proliferation of rat cerebellar granule cells in culture. These neurons express trkB and trkC, the putative neuronal receptors for brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) respectively. Binding studies using iodinated BDNF and NT-3 demonstrated that both BDNF and NT-3 bind to the cerebellar granule neurons with a similar affinity of approximately 2 x 10(-9) M. The number of receptors per granule cell was surprisingly high, approximately 30 x 10(-4) and 2 x 10(5) for BDNF and NT-3, respectively. Both NT-3 and BDNF elevated c-fos mRNA in the granule neurons, but only BDNF up-regulated the mRNA encoding the low-affinity neurotrophin receptor (p75). In contrast to NT-3, BDNF acted as a survival factor for the granule neurons. BDNF also induced sprouting of the granule neurons and significantly protected them against neurotoxicity induced by high (1 mM) glutamate concentrations. Cultured granule neurons also expressed low levels of BDNF mRNA which were increased by kainic acid, a glutamate receptor agonist. Thus, BDNF, but not NT-3, is a survival factor for cultured cerebellar granule neurons and activation of glutamate receptor(s) up-regulates BDNF expression in these cells.}, author = {Lindholm, Dan and Dechant, Georg and Heisenberg, Carl-Philipp J and Thoenen, Hans}, issn = {0953-816X}, journal = {European Journal of Neuroscience}, number = {11}, pages = {1455 -- 1464}, publisher = {Wiley-Blackwell}, title = {{Brain-derived neurotrophic factor is a survival factor for cultured rat cerebellar granule neurons and protects them against glutamate-induced neurotoxicity}}, doi = {10.1111/j.1460-9568.1993.tb00213.x}, volume = {5}, year = {1993}, }