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ABSTRACT: Synaptic development is an activity-dependent process utilizing coordinated network activity to drive synaptogenesis and subsequent refinement of immature connections. Hippocampal CA3 pyramidal neurons (PYRs) exhibit intense burst firing (BF) early in development, concomitant with the period of mossy fibre (MF) development. However, whether developing MF–PYR synapses utilize PYR BF to promote MF synapse maturation remains unknown. Recently, we demonstrated that transient tonic depolarization of postsynaptic PYRs induces a persistent postsynaptic form of long-term depression (depolarization-induced long-term depression, DiLTD) at immature MF–PYR synapses. DiLTD induction is NMDAR independent but does require postsynaptic Ca2+ influx through L-type voltage gated Ca2+ channels (L-VGCCs), and is expressed as a reduction in AMPAR function through the loss of GluR2-lacking AMPARs present at immature MF–PYR synapses. Here we examined whether more physiologically relevant phasic L-VGCC activation by PYR action potential (AP) BF activity patterns can trigger DiLTD. Using combined electrophysiological and Ca2+ imaging approaches we demonstrate that PYR BF effectively drives L-VGCC activation and that brief periods of repetitive PYR BF, produced by direct current injection or intrinsic network activity induces NMDAR-independent LTD by promoting Ca2+ influx through the activated L-VGCCs. This BF induced LTD, just like DiLTD, is specific for developing MF–PYR synapses, is PICK1 dependent, and is expressed postsynaptically. Our results demonstrate that DiLTD can be induced by phasic L-VGCC activation driven by PYR BF, suggesting the engagement of natural PYR network activity patterns for MF synapse maturation.
The Journal of Physiology 09/2009; 587(18):4441 - 4454. · 4.72 Impact Factor
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ABSTRACT: Proliferative oligodendrocyte progenitor cells (OPs) express large, delayed outward-rectifying K(+) currents (I(K)), whereas nondividing immature and mature oligodendrocytes display much smaller I(K). Here, we show that up-regulation of I(K) occurs in G(1) phase of the cell cycle in purified cultured OPs and is the result of an RNA synthesis-dependent, selective increase of the K(+) channel subunit proteins Kv1.3 and Kv1.5. In oligodendrocyte cells acutely isolated from developing rat brain, a decrease of cyclin D expression is observed as these cells mature along their lineage. This is accompanied by a decrease in Kv1.3 and Kv1.5 subunit expression, suggesting a role for these subunits in the proliferative potential of OPs in situ. I(K) expressed in OPs in subventricular zone and developing white matter in acutely isolated slice preparations were selectively blocked by antagonists of Kv1.3, illustrating the functional presence of this subunit in situ. Interestingly, Kv1.3 block inhibited S-phase entry of both purified OPs in culture and in tissue slice cultures. Thus, we employ both in vitro and in situ experimental approaches to show that (i) RNA-dependent synthesis of Kv1.3 and Kv1.5 subunit proteins occurs in G(1) phase of the OP cell cycle and is responsible for the observed increase in I(K), and (ii) currents through Kv1.3-containing channels play a crucial role in G(1)/S transition of proliferating OPs.
Proceedings of the National Academy of Sciences 03/2002; 99(4):2350-5. · 9.68 Impact Factor
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ABSTRACT: Sound features are blended together en route to the central nervous system before being discriminated for further processing by the cortical synaptic network. The mechanisms underlying this synaptic processing, however, are largely unexplored. Intracortical processing of the auditory signal was investigated by simultaneously recording from pairs of connected principal neurons in layer II/III in slices from A1 auditory cortex. Physiological patterns of stimulation in the presynaptic cell revealed two populations of postsynaptic events that differed in mean amplitude, failure rate, kinetics and short-term plasticity. In contrast, transmission between layer II/III pyramidal neurons in barrel cortex were uniformly of large amplitude and high success (release) probability (Pr). These unique features of auditory cortical transmission may provide two distinct mechanisms for discerning and separating transient from stationary features of the auditory signal at an early stage of cortical processing.
Nature Neuroscience 01/2002; 4(12):1230-7. · 15.53 Impact Factor
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ABSTRACT: Analysis of the Kv3 subfamily of K(+) channel subunits has lead to the discovery of a new class of neuronal voltage-gated K(+) channels characterized by positively shifted voltage dependencies and very fast deactivation rates. These properties are adaptations that allow these channels to produce currents that can specifically enable fast repolarization of action potentials without compromising spike initiation or height. The short spike duration and the rapid deactivation of the Kv3 currents after spike repolarization maximize the quick recovery of resting conditions after an action potential. Several neurons in the mammalian CNS have incorporated into their repertoire of voltage-dependent conductances a relatively large number of Kv3 channels to enable repetitive firing at high frequencies - an ability that crucially depends on the special properties of Kv3 channels and their impact on excitability.
Trends in Neurosciences 10/2001; 24(9):517-26. · 14.23 Impact Factor
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ABSTRACT: Local-circuit, gamma-aminobutyric acid-releasing inhibitory interneurons of the hippocampus and cortex have traditionally been considered as the regulators of principal neuron activity--the yin to the excitatory yang. Recent evidence indicates that, in addition to that role, their network connectivity and the properties of their intrinsic voltage-gated currents are finely tuned to permit inhibitory interneurons to generate and control the rhythmic output of large populations of both principal cells and other populations of inhibitory interneurons. This review brings together recently described properties and emerging principles of interneuron function that indicate a much more complex role for these cells than just providers of inhibition.
Nature reviews. Neuroscience 02/2001; 2(1):11-23. · 30.44 Impact Factor
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ABSTRACT: The axons of the dentate gyrus granule cells, the so-called mossy fibers, innervate their inhibitory interneuron and pyramidal neuron targets via both anatomically and functionally specialized synapses. Mossy fiber synapses onto inhibitory interneurons were comprised of either calcium-permeable (CP) or calcium-impermeable (CI) AMPA receptors, whereas only calcium-impermeable AMPA receptors existed at CA3 principal neuron synapses. In response to brief trains of high-frequency stimuli (20 Hz), pyramidal neuron synapses invariably demonstrated short-term facilitation, whereas interneuron EPSCs demonstrated either short-term facilitation or depression. Facilitation at all CI AMPA synapses was voltage independent, whereas EPSCs at CP AMPA synapses showed greater facilitation at -20 than at -80 mV, consistent with a role for the postsynaptic unblock of polyamines. At pyramidal cell synapses, mossy fiber EPSCs possessed marked frequency-dependent facilitation (commencing at stimulation frequencies >0.1 Hz), whereas EPSCs at either type of interneuron synapse showed only moderate frequency-dependent facilitation or underwent depression. Presynaptic metabotropic glutamate receptors (mGluRs) decreased transmission at all three synapse types in a frequency-dependent manner. However, after block of presynaptic mGluRs, transmission at interneuron synapses still did not match the dynamic range of EPSCs at pyramidal neuron synapses. High-frequency stimulation of mossy fibers induced long-term potentiation (LTP), long-term depression (LTD), or no change at pyramidal neuron synapses, interneuron CP AMPA synapses, and CI AMPA synapses, respectively. Induction of LTP or LTD altered the short-term plasticity of transmission onto both pyramidal cells and interneuron CP AMPA synapses by a mechanism consistent with changes in release probability. These data reveal differential mechanisms of transmission at three classes of mossy fiber synapse made onto distinct targets.
Journal of Neuroscience 12/2000; 20(22):8279-89. · 7.11 Impact Factor
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ABSTRACT: Histamine-containing neurons of the tuberomammilary nucleus project to the hippocampal formation to innervate H1 and H2 receptors on both principal and inhibitory interneurons. Here we show that H2 receptor activation negatively modulates outward currents through Kv3.2-containing potassium channels by a mechanism involving PKA phosphorylation in inhibitory interneurons. PKA phosphorylation of Kv3.2 lowered the maximum firing frequency of inhibitory neurons, which in turn negatively modulated high-frequency population oscillations recorded in principal cell layers. All these effects were absent in a Kv3.2 knockout mouse. These data reveal a novel pathway for histamine-dependent regulation of high-frequency oscillations within the hippocampal formation.
Nature Neuroscience 09/2000; 3(8):791-8. · 15.53 Impact Factor
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ABSTRACT: Target-specific expression of pre- and postsynaptic mechanisms of synaptic transmission has been shown in a variety of central neurons by a number of laboratories. These data have demonstrated that synaptic transmission between single axons diverging onto distinct target neurons can behave independently, differentially influencing activity in the target neuron. Similarly, single neurons are capable of manufacturing molecularly distinct ligand-gated receptors and targeting them to synapses innervated by distinct converging afferent projections. A picture is emerging consistent with a role for both pre- and postsynaptic mechanisms in influencing the target-specific nature of transmission at numerous diverse synapses throughout the mammalian CNS. This target specificity adds another level of complexity in unravelling the roles played by individual neurons within a computational network. To begin to understand the coordinated activity of large ensembles of neurons it is becoming clear that the nature of transmission between individual pre- and postsynaptic elements within a circuit must first be understood for each and every neural element involved.
The Journal of Physiology 06/2000; 525 Pt 1:41-51. · 4.72 Impact Factor
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ABSTRACT: Human cortical heterotopia and neuronal migration disorders result in epilepsy; however, the precise mechanisms remain elusive. Here we demonstrate severe neuronal dysplasia and heterotopia throughout the granule cell and pyramidal cell layers of mice containing a heterozygous deletion of Lis1, a mouse model of human 17p13.3-linked lissencephaly. Birth-dating analysis using bromodeoxyuridine revealed that neurons in Lis1+/- murine hippocampus are born at the appropriate time but fail in migration to form a defined cell layer. Heterotopic pyramidal neurons in Lis1+/- mice were stunted and possessed fewer dendritic branches, whereas dentate granule cells were hypertrophic and formed spiny basilar dendrites from which the principal axon emerged. Both somatostatin- and parvalbumin-containing inhibitory neurons were heterotopic and displaced into both stratum radiatum and stratum lacunosum-moleculare. Mechanisms of synaptic transmission were severely disrupted, revealing hyperexcitability at Schaffer collateral-CA1 synapses and depression of mossy fiber-CA3 transmission. In addition, the dynamic range of frequency-dependent facilitation of Lis1+/- mossy fiber transmission was less than that of wild type. Consequently, Lis1+/- hippocampi are prone to interictal electrographic seizure activity in an elevated [K(+)](o) model of epilepsy. In Lis1+/- hippocampus, intense interictal bursting was observed on elevation of extracellular potassium to 6.5 mM, a condition that resulted in only minimal bursting in wild type. These anatomical and physiological hippocampal defects may provide a neuronal basis for seizures associated with lissencephaly.
Journal of Neuroscience 05/2000; 20(7):2439-50. · 7.11 Impact Factor
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C J McBain
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ABSTRACT: In the CA1 region of the hippocampus pyramidal neuron basilar dendrites extend into the stratum oriens-alveus while the apical dendrites project deep into the stratum lacunosum-moleculare, a distance several hundred micrometres in extent. This extended dendritic arbor provides a large surface area for afferent input. For example, the axons of CA3 pyramidal neurons synapse onto pyramidal cell dendritic spines across approximately 2/3 of the apical dendritic tree. In contrast a diverse population of local-circuit GABAergic inhibitory interneurons selectively innervate specific postsynaptic domains of principal cells (for review see Freund & Buzsaki, 1996). These cells target their axons either to the axon initial segment, somata, or proximal and distal dendrites, with each cell type implicated in a particular operational role. However, rigid classification of the numerous subpopulations has been problematic (see Parra et al. 1998 for further discussion).
The Journal of Physiology 04/2000; 524 Pt 1:2. · 4.72 Impact Factor
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ABSTRACT: SNAP-25, synaptosomal associated protein of 25 kDa, is reported to be a t-SNARE (target receptor associated with the presynaptic plasma membrane) involved in the docking and fusion of synaptic vesicles. We present here the first ultrastructural localization of SNAP-25 in intact neurons by pre-embedding EM immunocytochemistry in rat brains, hippocampal slice cultures, and PC12 cells. In differentiated neurons, SNAP-25 labeling was clearly membrane-associated. The labeling was most prominent in the plasma membrane of axons and excluded from the plasma membranes of soma and dendrites. Furthermore, SNAP-25 did not appear to be restricted to the synaptic junctions. SNAP-25 labeling was seen in the cytoplasm of the soma and large dendrites, mostly associated with the Golgi complexes. There were also some SNAP-25 labeled tubulo-vesicular structures in the cytoplasm of the soma and the axons, but rarely in the smaller dendrites. In PC12 cells, after 5-10 minutes of high potassium (75 mM) stimulation in the presence of HRP, SNAP-25 labeling appeared, additionally, on HRP-filled early endosomes. After a longer (20-30 minutes) HRP incubation, most of the later stage endosomes and lysosomes were loaded with HRP but they were negative for SNAP-25. These results suggest that SNAP-25 is sorted out of these late endosomal compartments, and that the bulk of the SNAP-25 protein is probably recycled back to the axolemma from the early endosomes. In contrast, in those samples which were incubated with HRP for longer periods, there were still some SNAP-25-positive vesicular structures which were HRP-negative. These structures most likely represent anterograde vesicles that carry newly synthesized SNAP-25 from the soma to the axolemma by axonal transport. SNAP-25 appears to be sorted at the Golgi complex to reach the axolemma specifically. Its widespread distribution all along the axolemma does not support the view of SNAP-25 as a t-SNARE limited for synaptic exocytosis.
Journal of Neurocytology 02/2000; 29(1):67-77. · 1.94 Impact Factor
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ABSTRACT: Neural cell development is regulated by membrane ion channel activity. We have previously demonstrated that cell membrane depolarization with veratridine or blockage of K+ channels with tetraethylammonium (TEA) inhibit oligodendrocyte progenitor (OP) proliferation and differentiation (); however the molecular events involved are largely unknown. Here we show that forskolin (FSK) and its derivative dideoxyforskolin (DFSK) block K+ channels in OPs and inhibit cell proliferation. The antiproliferative effects of TEA, FSK, DFSK, and veratridine were attributable to OP cell cycle arrest in G1 phase. In fact, (1) cyclin D accumulation in synchronized OP cells was not affected by K+ channel blockers or veratridine; (2) these agents prevented OP cell proliferation only if present during G1 phase; and (3) G1 blockers, such as rapamycin and deferoxamine, mimicked the anti-proliferative effects of K+ channel blockers. DFSK also prevented OP differentiation, whereas FSK had no effect. Blockage of K+ channels and membrane depolarization also caused accumulation of the cyclin-dependent kinase inhibitors p27(Kip1) and p21(CIP1) in OP cells. The antiproliferative effects of K+ channel blockers and veratridine were still present in OP cells isolated from INK4a-/- mice, lacking the cyclin-dependent kinase inhibitors p16(INK4a) and p19(ARF). Our results demonstrate that blockage of K+ channels and cell depolarization induce G1 arrest in the OP cell cycle through a mechanism that may involve p27(Kip1) and p21(CIP1) and further support the conclusion that OP cell cycle arrest and differentiation are two uncoupled events.
Journal of Neuroscience 08/1999; 19(13):5380-92. · 7.11 Impact Factor
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ABSTRACT: In the hippocampal formation GABAergic inhibitory interneurons have a major role in the synchronization of neuronal activity and are involved in the generation of large-scale network oscillations. Thus, interneurons function as a 'clock' that dictates when principal cells fire during suprathreshold excitatory drive. Interneurons receive strong excitatory innervation from glutamatergic neurons and it has been much debated whether these synapses show mechanisms of long-term plasticity similar to those found at principal-cell synapses. Recent findings support the lack of conventional forms of LTP and LTD in most interneurons, partly owing to the distinct anatomical and neurochemical features of interneuronal excitatory synapses. The uncommon properties of excitatory synapses on interneurons might be required for their functioning as accurate and reliable neuronal oscillators.
Trends in Neurosciences 06/1999; 22(5):228-35. · 14.23 Impact Factor
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ABSTRACT: We examined the pathways that link neurotransmitter receptor activation and cell cycle arrest in oligodendrocyte progenitors. We had previously demonstrated that glutamate receptor activation inhibits oligodendrocyte progenitor proliferation and lineage progression. Here, using purified oligodendrocyte progenitors and cerebellar slice cultures, we show that norepinephrine and the beta-adrenergic receptor agonist isoproterenol also inhibited the proliferation, but in contrast to glutamate, isoproterenol stimulated progenitor lineage progression, as determined by O4 and O1 antibody staining. This antiproliferative effect was specifically attributable to a beta-adrenoceptor-mediated increase in cyclic adenosine monophosphate, since analogs of this cyclic nucleotide mimicked the effects of isoproterenol on oligodendrocyte progenitor proliferation, while alpha-adrenoceptor agonists were ineffective. Despite the opposite effects on lineage progression, both isoproterenol and the glutamate receptor agonist kainate caused accumulation of the cyclin-dependent kinase inhibitors p27(Kip1)and p21(CIP1), and G1 arrest. Studies with oligodendrocyte progenitor cells from INK4a-/- mice indicated that the G1 cyclin kinase inhibitor p16(INK4a) as well as p19(ARF)were not required for agonist-stimulated proliferation arrest. Our results demonstrate that beta-adrenergic and glutamatergic receptor activation inhibit oligodendrocyte progenitor proliferation through a mechanism that may involve p27(Kip1) and p21(CIP1); but while neurotransmitter-induced accumulation of p27(Kip1) is associated with cell cycle arrest, it does not by itself promote oligodendrocyte progenitor differentiation.
Development 03/1999; 126(5):1077-90. · 6.60 Impact Factor
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ABSTRACT: Neurons of a distinct type in CA1 area stratum radiatum of the rat hippocampus have been found to express a direct cellular form of long-term potentiation (LTP, Maccaferri & McBain, 1996, J. Neurosci. 16, 5334), but their functional identity, i.e. whether interneuron or principal cell, remained unknown. Whole cell recording from hippocampal slices in vitro was combined with light and electron microscopy to answer this question. LTP was robustly induced by a pairing protocol and physiological properties were measured in radiatum giant cells (RGCs) using biocytin containing pipettes. Reconstruction of the cells' dendritic and axonal arbor revealed morphological properties similar to CA1 pyramidal cells with some characteristic differences. They typically had two large diameter apical dendrites, or when only one dendrite arose, it soon bifurcated. Apical dendrites formed a dendritic tuft in stratum lacunosum-moleculare and the dendrites, but not the somata, were densely covered with conventional spines. The axon arose from the basal pole of the soma, descended to stratum oriens and emitted several axon terminals bearing collaterals that travelled horizontally, remaining in stratum oriens. The main, myelinated axon trunks turned towards the fimbria. In the electron microscope axon terminals were found to form asymmetrical synapses on postsynaptic dendritic shafts and dendritic spines in stratum oriens. The dendrites received asymmetrical synapses, mostly on their spines. The axon initial segments also received several synapses, a feature never observed on interneurons. All the above characteristics support the conclusion that RGCs are excitatory principal neurons.
European Journal of Neuroscience 12/1998; 10(12):3813-22. · 3.63 Impact Factor
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ABSTRACT: Using the polyamine toxin philanthotoxin, which selectively blocks calcium-permeable AMPA receptors, we show that synaptic transmission onto single hippocampal interneurons occurs by afferent-specific activation of philanthotoxin-sensitive and -insensitive AMPA receptors. Calcium-permeable AMPA receptors are found exclusively at synapses from mossy fibers. In contrast, synaptic responses evoked by stimulation of CA3 pyramidal neurons are mediated by calcium-impermeable AMPA receptors. Both pathways converge onto single interneurons and can be discriminated with Group II mGluR agonists. Thus, single interneurons target AMPA receptors of different subunit composition to specific postsynaptic sites, providing a mechanism to increase the synapse-specific computational properties of hippocampal interneurons.
Nature Neuroscience 12/1998; 1(7):572-8. · 15.53 Impact Factor
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ABSTRACT: Heterozygous mutation or deletion of the beta subunit of platelet-activating factor acetylhydrolase (PAFAH1B1, also known as LIS1) in humans is associated with type I lissencephaly, a severe developmental brain disorder thought to result from abnormal neuronal migration. To further understand the function of PAFAH1B1, we produced three different mutant alleles in mouse Pafah1b1. Homozygous null mice die early in embryogenesis soon after implantation. Mice with one inactive allele display cortical, hippocampal and olfactory bulb disorganization resulting from delayed neuronal migration by a cell-autonomous neuronal pathway. Mice with further reduction of Pafah1b1 activity display more severe brain disorganization as well as cerebellar defects. Our results demonstrate an essential, dosage-sensitive neuronal-specific role for Pafah1b1 in neuronal migration throughout the brain, and an essential role in early embryonic development. The phenotypes observed are distinct from those of other mouse mutants with neuronal migration defects, suggesting that Pafah1b1 participates in a novel pathway for neuronal migration.
Nature Genetics 09/1998; 19(4):333-9. · 35.53 Impact Factor
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ABSTRACT: We tested the hypothesis that the neurotransmitter glutamate would influence glial proliferation and differentiation in a cytoarchitecturally intact system. Postnatal day 6 cerebellar slices were maintained in organotypic culture and treated with glutamate receptor agonists or antagonists. After dissociation, cells were stained with antibodies for different oligodendrocyte developmentally regulated antigens. Treatment of the slices with the glutamate receptor agonists kainate or alpha -amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid significantly decreased the percentage of LB1(+), NG2(+) and O4(+) cells, and their bromodeoxyuridine labeling index. The non-N-methyl-D-aspartate glutamate receptor antagonist 6,7-dinitroquinoxaline-2,3-dione increased the percentage and bromodeoxyuridine labeling of LB1(+), NG2(+) and O4(+) cells. In intact slices, RNA levels of the oligodendrocyte gene for 2',3'-cyclic nucleotide 3'-phosphodiesterase were decreased by kainate and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, and increased by 6,7-dinitroquinoxaline-2,3-dione. The percentage of astrocytes was not modified by kainate, alpha -amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid or 6, 7-dinitroquinoxaline-2,3-dione. Treatment with the N-methyl-D-aspartate receptor antagonist 2-amino-5-phosphonopentanoic acid did not alter the percentage of O4(+) cells, nor their proliferation. Incubation with the gamma-aminobutyric acid receptor antagonist bicuculline did not modify the percentage of LB1(+), A2B5(+) and O4(+) cells. In purified cerebellar oligodendrocyte progenitor cells, glutamate receptor agonists blocked K+ currents, and inhibited cell proliferation and lineage progression. The K+ channel blocker tetraethylammonium also inhibited oligodendrocyte progenitor cell proliferation. These findings indicate that in rat cerebellar tissue slices: (i) glutamate specifically modulates oligodendrocyte but not astrocyte development through selective activation of alpha -amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors, and (ii) cell depolarization and blockage of voltage-dependent K+ channels is likely to be the triggering mechanism.
Development 09/1998; 125(15):2901-14. · 6.60 Impact Factor
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ABSTRACT: A variety of voltage-gated ion channels are expressed on principal cell dendrites and have been proposed to play a pivotal role in the regulation of dendritic excitability. Previous studies at the light microscopic level demonstrated that the K+ channel subunit Kv2.1 expression was polarized to the cell soma and dendrites of principal neurons throughout the central nervous system. Here, using double immunostaining we now show that Kv2.1 protein is similarly expressed in the majority of cortical and hippocampal parvalbumin, calbindin and somatostatin-containing inhibitory interneurons. At the electron microscopic level Kv2.1 immunoreactivity was primarily observed on the plasma membrane of the somata and proximal dendrites of both principal neurons and inhibitory interneurons; expression was low on smaller dendritic branches, and absent on axons and presynaptic terminals. Kv2.1 subunit expression was highly concentrated on the cell surface membrane immediately facing astrocytic processes. Kv2.1 expression was also concentrated in specific cytoplasmic compartments and on the subsurface cisterns underlying the plasma membrane facing astrocytes. In addition, Kv2.1 subunit immunoreactivity was associated with postsynaptic densities of a fraction of inhibitory symmetric synapses; while expression at asymmetric synapses was rare. These data demonstrate that channels formed by Kv2.1 subunits are uniquely positioned on the soma and principal dendrites of both pyramidal cells and inhibitory interneurons at sites immediately adjacent to astrocytic processes. This close apposition to astrocytes will ensure a rapid removal and limit the influence of K+ released into the extracellular space. This expression pattern suggests that channels formed by Kv2.1 are poised to provide a role in the regulation of neuronal dendritic excitability.
Neuroscience 05/1998; 84(1):37-48. · 3.38 Impact Factor
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ABSTRACT: Mossy fiber synaptic transmission at hippocampal CA3 pyramidal cells and interneurons was compared in rat brain slices to determine whether mossy terminals are functionally equivalent. Tetanic stimulation of mossy fibers induced long-term potentiation in pyramidal neurons but was either without effect or it induced depression at synapses onto interneurons. Unlike transmission onto pyramidal neurons, transmission onto interneurons was not potentiated after adenosine 3',5'-monophosphate (cAMP) activation. Furthermore, metabotropic glutamate receptor depression of transmission onto interneurons did not involve cAMP-dependent pathways. Thus, synaptic terminals arising from a common afferent pathway do not function as a single compartment but are specialized, depending on their postsynaptic target.
Science 03/1998; 279(5355):1368-70. · 31.20 Impact Factor
