Distribution by Scientific Domains
Distribution within Life Sciences

Kinds of Neurons

  • accumben neuron
  • active neuron
  • adrenergic neuron
  • adult neuron
  • affected neuron
  • afferent neuron
  • anterior horn neuron
  • auditory neuron
  • basal forebrain cholinergic neuron
  • brain neuron
  • brainstem neuron
  • c1 neuron
  • ca1 neuron
  • ca1 pyramidal neuron
  • ca3 pyramidal neuron
  • capsaicin-sensitive sensory neuron
  • cart neuron
  • catecholaminergic neuron
  • central neuron
  • cerebellar neuron
  • cerebral cortical neuron
  • certain neuron
  • cholinergic neuron
  • cns neuron
  • containing neuron
  • cord neuron
  • cortex neuron
  • cortical neuron
  • cortical pyramidal neuron
  • cultured cortical neuron
  • cultured hippocampal neuron
  • cultured neuron
  • cultured rat cortical neuron
  • cultured rat hippocampal neuron
  • da neuron
  • daergic neuron
  • differentiated neuron
  • dopamine neuron
  • dopaminergic neuron
  • dorsal horn neuron
  • dorsal root ganglion neuron
  • drg neuron
  • drn neuron
  • drosophila neuron
  • embryonic neuron
  • enteric neuron
  • entorhinal neuron
  • excitatory neuron
  • expressing neuron
  • forebrain cholinergic neuron
  • forebrain neuron
  • gaba neuron
  • gabaergic neuron
  • ganglion neuron
  • generated neuron
  • giant neuron
  • globu pallidu neuron
  • glutamatergic neuron
  • glycinergic neuron
  • gnrh neuron
  • granule neuron
  • hindbrain neuron
  • hippocampal ca1 pyramidal neuron
  • hippocampal neuron
  • hippocampal pyramidal neuron
  • horn neuron
  • human neuron
  • hydroxylase-positive neuron
  • hypothalamic neuron
  • identified neuron
  • ii neuron
  • immature neuron
  • immunoreactive neuron
  • inhibitory neuron
  • injured neuron
  • input neuron
  • intrinsic sensory neuron
  • labeled neuron
  • labelled neuron
  • lamina i neuron
  • large neuron
  • lower motor neuron
  • magnocellular neuron
  • many neuron
  • mature neuron
  • mechanosensory neuron
  • median neuron
  • medium spiny neuron
  • medium-sized spiny neuron
  • mesencephalic dopaminergic neuron
  • midbrain dopamine neuron
  • midbrain dopaminergic neuron
  • migrating neuron
  • mirror neuron
  • monoaminergic neuron
  • motor neuron
  • multipolar neuron
  • myenteric neuron
  • neocortical neuron
  • new neuron
  • newborn neuron
  • nigral dopaminergic neuron
  • nigral neuron
  • nigrostriatal neuron
  • nociceptive neuron
  • nodose ganglion neuron
  • noradrenergic neuron
  • normal neuron
  • nucleus neuron
  • olfactory neuron
  • olfactory receptor neuron
  • olfactory sensory neuron
  • orexin neuron
  • other neuron
  • output neuron
  • pallidal neuron
  • pallidu neuron
  • parasympathetic neuron
  • parvocellular neuron
  • peripheral neuron
  • peripheral sensory neuron
  • photoreceptor neuron
  • pontine neuron
  • positive neuron
  • post-mitotic neuron
  • postmitotic neuron
  • postsynaptic neuron
  • preganglionic neuron
  • premotor neuron
  • presynaptic neuron
  • primary afferent neuron
  • primary cortical neuron
  • primary hippocampal neuron
  • primary neuron
  • primary sensory neuron
  • principal neuron
  • projecting neuron
  • projection neuron
  • purkinje neuron
  • pvn neuron
  • pyramidal neuron
  • raphe neuron
  • rat cortical neuron
  • rat hippocampal neuron
  • rat hippocampal pyramidal neuron
  • rat neuron
  • rat primary cortical neuron
  • receptor neuron
  • recorded neuron
  • relay neuron
  • retinal neuron
  • root ganglion neuron
  • same neuron
  • scg neuron
  • scn neuron
  • second-order neuron
  • sensory neuron
  • septal cholinergic neuron
  • septal neuron
  • serotonergic neuron
  • single neuron
  • small neuron
  • spinal cord neuron
  • spinal motor neuron
  • spinal neuron
  • spiny neuron
  • spiral ganglion neuron
  • stained neuron
  • striatal neuron
  • striatal projection neuron
  • submucosal neuron
  • survival motor neuron
  • sympathetic neuron
  • target neuron
  • th-positive neuron
  • thalamic neuron
  • total neuron
  • tract neuron
  • trigeminal neuron
  • tunel-positive neuron
  • vulnerable neuron
  • young neuron

  • Terms modified by Neurons

  • neuron activity
  • neuron axon extension
  • neuron culture
  • neuron death
  • neuron degeneration
  • neuron density
  • neuron development
  • neuron disease
  • neuron dysfunction
  • neuron excitability
  • neuron intrinsic
  • neuron lead
  • neuron loss
  • neuron marker
  • neuron migration
  • neuron number
  • neuron only
  • neuron population
  • neuron precursor
  • neuron soma
  • neuron specific enolase
  • neuron survival
  • neuron system
  • neuron type

  • Selected Abstracts


    ALCOHOLISM, Issue 2008
    Amina E Jamali
    Alcohol exposure to the developing brain compromises both neurons and glial functions. While neurons are considered the primary targets, microglia may play a neurotoxic role in this process. Previous studies demonstrated that neuron death is due to oxidative stress and mitochondrially mediated (Intrinsic). These studies showed a rapid increase (within minutes) in reactive oxygen species (ROS). Due to the diffusive nature of ethanol and multiple sources of free radicals, we sought to determine the primary source of superoxide targeted by ethanol. Confocal studies of neurons suggest that the superoxide radicals may originate from the mitochondria. Using whole neurons in a luminol-based chemiluminescence assay (Diogenes) we detected superoxide radicals in the extracellular mileu. We observed a two-three fold transient increase in the steady state generation of superoxide radicals between 20 minutes to one hour of ethanol exposure (4mg/ml). However, the presence of Rotenone (mitochondrial complex I inhibitor) and DPI (an inhibitor of all flavinoids) blocked the release of these superoxide radicals. Interestingly, cortical microglia treated identically with ethanol, showed a greater than five fold increase in superoxide generation with a maximum at one hour. Moreover, since ethanol is known to induce hydrogen peroxide generation, it was used as a mimetic. Hydrogen peroxide also induced the production of superoxide different time kinetics. Thus, together these data demonstrate that ethanol induces the steady state production of superoxide radicals in the extracellular mileu in a mitochondrial dependent manner. Since NOX2 an NADPH oxidase is expressed in neurons, it is a potential candidate for the secondary sites of superoxide generation. The ROS network between mitochondria and the plasma membrane highlights new therapeutical targets to counter ethanol toxicity. [source]


    ES Louise Faber
    SUMMARY 1SK channels are small-conductance calcium-activated potassium channels that are widely expressed in neurons. The traditional view of the functional role of SK channels is in mediating one component of the after-hyperpolarization that follows action potentials. Calcium influx via voltage-gated calcium channels active during action potentials opens SK channels and the resultant hyperpolarization lowers the firing frequency of action potentials in many neurons. 2Recent advances have shown that, in addition to controlling action potential firing frequency, SK channels are also important in regulating dendritic excitability, synaptic transmission and synaptic plasticity. 3In accordance with their role in modulating synaptic plasticity, SK channels are also important in regulating several learning and memory tasks and may also play a role in a number of neurological disorders. 4The present review discusses recent findings on the role of SK channels in central neurons. [source]


    Paul P Bertrand
    SUMMARY 1.,The enteric nervous system (ENS) is present in the wall of the gastrointestinal tract and contains all the functional classes of neuron required for complete reflex arcs. One of the most important and intriguing classes of neuron is that responsive to sensory stimuli: sensory neurons with cell bodies intrinsic to the ENS. 2.,These neurons have three outstanding and interrelated features: (i) reciprocal connections with each other; (ii) a slow excitatory post-synaptic potential (EPSP) resulting from high-speed firing in other sensory neurons; and (iii) a large after-hyperpolarizing potential (AHP) at the soma. Slow EPSP depolarize the cell body, generate action potentials (APs) and reduce the AHP. Conversely, the AHP limits the firing rate and, hence, reduces transmission of slow EPSP. 3.,Processing of sensory information starts at the input terminals as different patterns of APs depending on the sensory modality and recent sensory history. At the soma, the ability to fire APs and, hence, drive outputs is also strongly determined by the recent firing history of the neuron (through the AHP) and network activity (through the slow EPSP). Positive feedback within the population of intrinsic sensory neurons means that the network is able to drive outputs well beyond the duration of the stimuli that triggered them. 4.,Thus, sensory input and subsequent reflex generation are integrated over several hierarchical levels within the network on intrinsic sensory neurons. [source]

    Inhibitory Effect of Lamotrigine on A-type Potassium Current in Hippocampal Neuron,Derived H19-7 Cells

    EPILEPSIA, Issue 7 2004
    Chin-Wei Huang
    Summary:,Purpose: We investigated the effects of lamotrigine (LTG) on the rapidly inactivating A-type K+ current (IA) in embryonal hippocampal neurons. Methods: The whole-cell configuration of the patch-clamp technique was applied to investigate the ion currents in cultured hippocampal neuron,derived H19-7 cells in the presence of LTG. Effects of various related compounds on IA in H19-7 cells were compared. Results: LTG (30 ,M,3 mM) caused a reversible reduction in the amplitude of IA. The median inhibitory concentration (IC50) value required for the inhibition of IA by LTG was 160 ,M. 4-Aminopyridine (1 mM), quinidine (30 ,M), and capsaicin (30 ,M) were effective in suppressing the amplitude of IA, whereas tetraethylammonium chloride (1 mM) and gabapentin (100 ,M) had no effect on it. The time course for the inactivation of IA was changed to the biexponential process during cell exposure to LTG (100 ,M). LTG (300 ,M) could shift the steady-state inactivation of IA to a more negative membrane potential by approximately ,10 mV, although it had no effect on the slope of the inactivation curve. Moreover, LTG (100 ,M) produced a significant prolongation in the recovery of IA inactivation. Therefore in addition to the inhibition of voltage-dependent Na+ channels, LTG could interact with the A-type K+ channels to suppress the amplitude of IA. The blockade of IA by LTG does not simply reduce current magnitude, but alters current kinetics, suggesting a state-dependent blockade. LTG might have a higher affinity to the inactivated state than to the resting state of the IA channel. Conclusions: This study suggests that in hippocampal neurons, during exposure to LTG, the LTG-mediated inhibition of these K+ channels could be one of the ionic mechanisms underlying the increased neuronal excitability. [source]

    Striatal modulation of cAMP-response-element-binding protein (CREB) after excitotoxic lesions: implications with neuronal vulnerability in Huntington's disease

    Carmela Giampà
    Abstract Recent evidence has shown that the activity of cAMP responsive element-binding protein (CREB) and of CREB-binding protein (CBP) is decreased in Huntington's disease (HD) [Steffan et al. (2000)Proc. Natl Acad. Sci. USA, 97, 6763,6768; Gines et al. (2003)Hum. Mol. Genet., 12, 497,508; Rouaux et al. (2004) Biochem. Pharmacol., 68, 1157,1164; Sugars et al. (2004)J. Biol. Chem., 279, 4988,4999]. Such decrease is thought to reflect the impaired energy metabolism observed in a HD mouse model, where a decline in striatum cAMP levels has been observed [Gines et al. (2003)Hum. Mol. Genet., 12, 497,508]. Increased levels of CREB have also been demonstrated to exert neuroprotective functions [Lonze & Ginty (2002)Neuron, 35, 605,623; Lonze et al. (2002)Neuron, 34, 371,385]. Our study aimed to investigate the distribution of CREB in the neuronal subpopulations of the striatum in normal rats compared to the HD model of quinolinic acid lesion. Twenty-five Wistar rats were administered quinolinic acid 100 mm into the right striatum, and killed after 24 h, 48 h, 1 week, 2 weeks, and six weeks, respectively. The contralateral striata were used as controls. Dual-label immunofluorescence was employed using antibodies against phosphorylated CREB and each of the different neuronal subpopulations markers. Our results show that activated CREB levels decrease progressively in projection neurons and parvalbumin (PARV) and calretinin (CALR) interneurons, whereas such levels remain stable in cholinergic and somatostatin interneurons. Thus, we speculate that the ability of cholinergic interneurons to maintain their levels of CREB after excitotoxic lesions is one of the factors determining their protection in Huntington's disease. [source]

    Cloning, distribution and functional analysis of the type III sodium channel from human brain

    Yu Hua Chen
    Abstract The type III voltage-gated sodium channel was cloned from human brain. The full-length cDNA has 89% identity with rat type III, and the predicted protein (1951 amino acids) has 55 differences. The expression pattern of human type III mRNA was determined in adult brain tissue and, in contrast to rat, was detected in many regions, including caudate nucleus, cerebellum, hippocampus and frontal lobe. The human type III channel was stably expressed in Chinese hamster ovary (CHO) cells and its biophysical properties compared to the human type II channel using identical conditions. The voltage dependence and kinetics of activation were found to be similar to that of type II. The kinetics of inactivation of the two human subtypes were also similar. However, type III channels inactivated at more hyperpolarized potentials and were slower to recover from inactivation than type II. When expressed in human embryonic kidney (HEK293T) cells, type III channels produced currents with a prominent persistent component, which were similar to those reported for rat type II [Ma et al. (1997) Neuron, 19, 443,452]. However, unlike type II, this was prominent even in the absence of coexpressed G-proteins, suggesting type III may adopt this gating mode more readily. The distinct properties of the channel, together with its wide distribution in adult brain, suggest that in humans, type III may have important physiological roles under normal, and perhaps also pathological conditions. [source]

    A BAC transgenic mouse model to analyze the function of astroglial SPARCL1 (SC1) in the central nervous system

    GLIA, Issue 9 2008
    Jill M. Weimer
    Abstract Extracellular matrix associated Sparc-like 1 (SC1/SPARCL1) can influence the function of astroglial cells in the developing and mature central nervous system (CNS). To examine SC1's significance in the CNS, we generated a BAC transgenic mouse model in which Sc1 is expressed in radial glia and their astrocyte derivatives using the astroglial-specific Blbp (Brain-lipid binding protein; [Feng et al., (1994) Neuron 12:895,908]) regulatory elements. Characterization of these Blbf-Sc1 transgenic mice show elevated Sc1 transcript and protein in an astroglial selective pattern throughout the CNS. This model provides a novel in vivo system for evaluating the role of SC1 in brain development and function, in general, and for understanding SC1's significance in the fate and function of astroglial cells, in particular. © 2008 Wiley-Liss, Inc. [source]

    Calcium signaling in specialized glial cells,

    GLIA, Issue 7 2006
    Monica R. Metea
    Abstract This article reviews calcium signaling in three specialized types of glial cells: Müller cells of the retina, Bergmann glial cells of the cerebellum, and radial glial cells of the developing cortex. Müller cells generate spontaneous and neuronal activity-evoked increases in Ca2+. Neuron to Müller cell signaling is mediated by neuronal release of ATP and activation of glial P2Y receptors. Müller cells, in turn, modulate neuronal excitability and mediate vasomotor responses. Bergmann glial cells also generate spontaneous and activity-evoked Ca2+ increases. Neuron to Bergmann glia signaling is mediated by neuronal release of nitric oxide, noradrenaline, and glutamate. In Bergmann glia, Ca2+ increases control the structural and functional interactions between these cells and Purkinje cell synapses. In the ventricular zone of the developing cortex, radial glial cells generate spontaneous Ca2+ increases that propagate as Ca2+ waves through clusters of neighboring glial cells. These Ca2+ increases control cell proliferation and neurogenesis. © 2006 Wiley-Liss, Inc. [source]

    Neuron,Glia Signaling in Trigeminal Ganglion: Implications for Migraine Pathology

    HEADACHE, Issue 7 2007
    Srikanth Thalakoti BS
    Objective.,The goal of this study was to investigate neuronal,glial cell signaling in trigeminal ganglia under basal and inflammatory conditions using an in vivo model of trigeminal nerve activation. Background.,Activation of trigeminal ganglion nerves and release of calcitonin gene-related peptide (CGRP) are implicated in the pathology of migraine. Cell bodies of trigeminal neurons reside in the ganglion in close association with glial cells. Neuron,glia interactions are involved in all stages of inflammation and pain associated with several central nervous system (CNS) diseases. However, the role of neuron,glia interactions within the trigeminal ganglion under normal and inflammatory conditions is not known. Methods.,Sprague,Dawley rats were utilized to study neuron,glia signaling in the trigeminal ganglion. Initially, True Blue was used as a retrograde tracer to localize neuronal cell bodies in the ganglion by fluorescent microscopy and multiple image alignment. Dye-coupling studies were conducted under basal conditions and in response to capsaicin injection into the TMJ capsule. S100B and p38 expression in neurons and glia were determined by immunohistochemistry following chemical stimulation. CGRP levels in the ganglion were measured by radioimmunoassay in response to capsaicin. In addition, the effect of CGRP on the release of 19 different cytokines from cultured glial cells was investigated by protein microarray analysis. Results.,In unstimulated control animals, True Blue was detected primarily in neuronal cell bodies localized in clusters within the ganglion corresponding to the V3 region (TMJ capsule), V2 region (whisker pad), or V1 region (eyebrow and eye). However, True Blue was detected in both neuronal cell bodies and adjacent glia in the V3 region of the ganglion obtained from animals injected with capsaicin. Dye movement into the surrounding glia correlated with the time after capsaicin injection. Chemical stimulation of V3 trigeminal nerves was found to increase the expression of the inflammatory proteins S100B and p38 in both neurons and glia within the V3 region. Unexpectedly, increased levels of these proteins were also observed in the V2 and V1 regions of the ganglion. CGRP and the vesicle docking protein SNAP-25 were colocalized in many neuronal cell bodies and processes. Decreased CGRP levels in the ganglion were observed 2 hours following capsaicin stimulation. Using protein microarray analysis, CGRP was shown to differentially regulate cytokine secretion from cultured trigeminal ganglion glia. Conclusions.,We demonstrated that activation of trigeminal neurons leads to changes in adjacent glia that involve communication through gap junctions and paracrine signaling. This is the first evidence, to our knowledge, of neuron,glia signaling via gap junctions within the trigeminal ganglion. Based on our findings, it is likely that neuronal,glial communication via gap junctions and paracrine signaling are involved in the development of peripheral sensitization within the trigeminal ganglion and, thus, are likely to play an important role in the initiation of migraine. Furthermore, we propose that propagation of inflammatory signals within the ganglion may help to explain commonly reported symptoms of comorbid conditions associated with migraine. [source]

    Canine Spinal Cord Neuron and Axon Myelin Sheath Morphometry

    A. C. De Francischini Carvalho
    Summary This inedited morphometric study has been developed from healthy canine spinal cord neuron cytoplasm and nucleus, and white matter axonal myelin sheath, from cervical, thoracic and lumbar regions. For the morphometric study, the parameters were area, perimeter, maximum and minimum diameters and roundness for neurons and myelin thickness for axon. For each parameter, 300 neurons were analysed. The results revealed that lumbar neurons had the highest mean values for the analysed parameters, indicating the presence of large neurons in this region, with large axons as a result of myelin thickness, which is proportional to axon calibre. We conclude that these morphometric results can contribute for the establishment of normal patterns, for canine spinal cord cervical, thoracic and lumbar segments. [source]

    Relationship between GABAergic interneurons migration and early neocortical network activity

    Ana D. de Lima
    Abstract Available evidence converges to suggest that during the early development of the cerebral cortex, the emergence of the spontaneous network activity chronologically overlap with the end of the cell migration period in the developing cortex. We approached the functional regulation of neuronal migration in a culture model of neocortical networks, using time lapses to detect migratory movements, calcium-imaging to assess the activity of migratory neurons, and immunocytochemical methods to identify the migratory cells retrospectively. In cell cultures, early physiological development and cell migration are reproduced at a local network level, thus allowing the study of the interrelationships between cell migration and network development independent of the topographical complexity. Neurons migrate at least until 12 days in vitro and GABAergic neurons migrate faster compared with non-GABAergic neurons. A decline of migratory activity was coincident with the development of spontaneous synchronous network activity. Migrating interneurons did not participate in synchronous network activity, but interneurons that ended cell migration during observation time frequently engaged in synchronous activity within less than an hour. Application of GABAA and ionotropic glutamate receptor antagonists significantly increased the number of migrating GABAergic neurons without changing the dynamics of the migratory movements. Thus, neurotransmitters released by early network activity might favor the termination of neuronal migration. These results reinforce the idea that network activity plays an important role in the development of late-born GABAergic cells. © 2008 Wiley Periodicals, Inc. Develop Neurobiol, 2009 [source]

    GABAB receptor expression and function in olfactory receptor neuron axon growth

    Catherine A. Priest
    Abstract Neurotransmitters have been implicated in regulating growth cone motility and guidance in the developing nervous system. Anatomical and electrophysiological studies show the presence of functional GABAB receptors on adult olfactory receptor neuron (ORN) nerve terminals. Using antisera against the GABAB R1a/b receptor isoforms we show that developing mouse olfactory receptor neurons express GABAB receptors from embryonic day 14 through to adulthood. GABAB receptors are present on axon growth cones from both dissociated ORNs and olfactory epithelial explants. Neurons in the olfactory bulb begin to express glutamic acid decarboxylase (GAD), the synthetic enzyme for GABA, from E16 through to adulthood. When dissociated ORNs were cultured in the presence of the GABAB receptor agonists, baclofen or SKF97541, neurite outgrowth was significantly reduced. Concurrent treatment of the neurons with baclofen and the GABAB receptor antagonist CGP54626 prevented the inhibitory effects of baclofen on ORN neurite outgrowth. These results show that growing ORN axons express GABAB receptors and are sensitive to the effects of GABAB receptor activation. Thus, ORNs in vivo may detect GABA release from juxtaglomerular cells as they enter the glomerular layer and use this as a signal to limit their outgrowth and find synaptic targets in regeneration and development. © 2004 Wiley Periodicals, Inc. J Neurobiol 60:154,165, 2004 [source]

    Nicotinic synapses formed between chick ciliary ganglion neurons in culture resemble those present on the neurons in vivo

    Min Chen
    Abstract We studied nicotinic synapses between chick ciliary ganglion neurons in culture to learn more about factors influencing their formation and receptor subtype dependence. After 4,8 days in culture, nearly all neurons displayed spontaneous excitatory postsynaptic currents (sEPSCs), which occurred at about 1 Hz. Neurons treated with tetrodotoxin displayed miniature EPSCs (mEPSCs), but these occurred at low frequency (0.1 Hz), indicating that most sEPSCs are actually impulse driven. The sEPSCs could be classified by decay kinetics as fast, slow, or biexponential and, reminiscent of the situation in vivo, were mediated by two major nicotinic acetylcholine receptor (AChR) subtypes. Fast sEPSCs were blocked by ,-bungarotoxin (,Bgt), indicating dependence on ,Bgt-AChRs, most of which are ,7 subunit homopentamers. Slow sEPSCs were unaffected by ,Bgt, and were blocked instead by the ,3/,2-selective ,-conotoxin-MII (,CTx-MII), indicating dependence on ,3*-AChRs, which lack ,7 and contain ,3 subunits. Biexponential sEPSCs were mediated by both ,Bgt- and ,3*-AChRs because they had fast and slow components qualitatively similar to those comprising simple events, and these were reduced by ,Bgt and blocked by ,CTx-MII, respectively. Fluorescence labeling experiments revealed both ,Bgt- and ,3*-AChR clusters on neuron somata and neurites. Colabeling with antisynaptic vesicle protein antibody suggested that some ,3*-AChR clusters, and a few ,Bgt-AChR clusters are associated with synaptic sites, as is the case in vivo. These findings demonstrate the utility of ciliary ganglion neuron cultures for studying the regulation of nicotinic synapses, and suggest that mixed AChR subtype synapses characteristic of the neurons in vivo can form in the absence of normal inputs or targets. © 2001 John Wiley & Sons, Inc. J Neurobiol 47: 265,279, 2001 [source]

    The mechanisms that underlie glucose sensing during hypoglycaemia in diabetes

    DIABETIC MEDICINE, Issue 5 2008
    R. McCrimmon
    Abstract Hypoglycaemia is a frequent and greatly feared side-effect of insulin therapy, and a major obstacle to achieving near-normal glucose control. This review will focus on the more recent developments in our understanding of the mechanisms that underlie the sensing of hypoglycaemia in both non-diabetic and diabetic individuals, and how this mechanism becomes impaired over time. The research focus of my own laboratory and many others is directed by three principal questions. Where does the body sense a falling glucose? How does the body detect a falling glucose? And why does this mechanism fail in Type 1 diabetes? Hypoglycaemia is sensed by specialized neurons found in the brain and periphery, and of these the ventromedial hypothalamus appears to play a major role. Neurons that react to fluctuations in glucose use mechanisms very similar to those that operate in pancreatic B- and A-cells, in particular in their use of glucokinase and the KATP channel as key steps through which the metabolic signal is translated into altered neuronal firing rates. During hypoglycaemia, glucose-inhibited (GI) neurons may be regulated by the activity of AMP-activated protein kinase. This sensing mechanism is disturbed by recurrent hypoglycaemia, such that counter-regulatory defence responses are triggered at a lower glucose level. Why this should occur is not yet known, but it may involve increased metabolism or fuel delivery to glucose-sensing neurons or alterations in the mechanisms that regulate the stress response. [source]

    Carbonic Anhydrase Inhibitor Sulthiame Reduces Intracellular pH and Epileptiform Activity of Hippocampal CA3 Neurons

    EPILEPSIA, Issue 5 2002
    Tobias Leniger
    Summary: ,Purpose: Sulthiame is a carbonic anhydrase (CA) inhibitor with an anticonvulsant effect in the treatment of benign and symptomatic focal epilepsy in children. The aim of the study was to elucidate the mode of action of sulthiame with respect to possible changes of intracellular pH (pHi) that might develop along with sulthiame's anticonvulsant properties. Methods: The effects of sulthiame (a) on pHi of 2,,7-bis(2-carboxyethyl)-5(6)-carboxyfluorescein-acetoxymetyl ester (BCECF-AM) loaded CA3 neurones as well as (b) on epileptiform activity (induced by 50 ,M 4-aminopyridine) were compared with those of the CA inhibitors acetazolamide and benzolamide. Results: In the majority of neurons, sulthiame (1.0,1.5 mM; n = 8) as well as the membrane permeant acetazolamide (0.5,1.0 mM; n = 6) reversibly decreased pHi by 0.18 ± 0.05 (SD) and 0.17 ± 0.10 (SD) pH units, respectively, within 10 min. The poor membrane permeant benzolamide (1.0,2.0 mM) had no influence on pHi (n = 8). Sulthiame (1.0,2.5 mM) and acetazolamide (1.0,2.0 mM) reversibly reduced the frequency of action potentials and epileptiform bursts after 10,15 min (n = 9, n = 7), whereas benzolamide (1.0,2.0 mM) had no effect (n = 6). Conclusions: The results suggest that sulthiame acts as a membrane-permeant CA inhibitor whose beneficial effect on epileptiform activity results at least in part from a modest intracellular acidosis of central neurons. [source]

    Enhanced Calcium Influx in Hippocampal CA3 Neurons of Spontaneously Epileptic Rats

    EPILEPSIA, Issue 3 2001
    Hiroko Amano
    Summary: ,Purpose: The spontaneously epileptic rat (SER: tm/tm, zi/zi) shows both absence-like seizures and tonic convulsions. Our previous electrophysiologic studies have demonstrated that SER has abnormal excitability of hippocampal CA3 neurons, which shows a long-lasting depolarization shift by a single stimulation of mossy fibers, probably resulting from the Ca2+ channel abnormalities. The present study was performed to determine whether Ca2+ influx is actually enhanced in the CA3 area of SER. Methods: Hippocampal slices were prepared from normal Wistar rats and SER aged 11,16 weeks old, when the epileptic seizures had been observed, and loaded with fura-2AM. Intracellular Ca2+ concentration ([Ca2+]i) was monitored as the ratio of fluorescence intensities excited at wavelengths of 340 and 380 nm (RF340/F380) with photometric devices. Results: High K+ (10,60 mM) applied to the bath for 2 min increased [Ca2+]i in hippocampal CA1, CA3, and dentate gyrus (DG) areas of both the normal rats and SER in a concentration-dependent manner. However, the high K+,induced increase in [Ca2+]i was significantly more pronounced in the CA3 area of the SER than in that of the normal animals, whereas there were no significant differences in high K+,induced increases of [Ca2+]i in CA1 or DG between the SER and controls. The high K+,induced increases in [Ca2+]i of CA1, CA3, and DG were inhibited by nifedipine (1,10 nM), a Ca2+ channel antagonist in both SER and controls. However, the inhibition of the high K+,induced increase in [Ca2+]i by nifedipine (1 nM) was significantly greater in the CA3 area of SER than that of controls. Conclusions: These findings suggest that Ca2+ influx through the L-type Ca2+ channels is much greater in the CA3 area of SER than in that of normal animals and is involved in the epileptic seizures of the SER. [source]

    Abnormal Excitability of Hippocampal CA3 Neurons in Noda Epileptic Rat (NER): Alteration of Seizure with Aging

    EPILEPSIA, Issue 2000
    Ryosuke Hanaya
    Purpose: Noda epileptic rat (NER), a mutant found in thc colony of Crj:Wistar rats, spontaneously shows tonic-clonic convulsions approximately once every 30 hours from 8,16 weeks of age. A long-lasting dcpolarization shift accompanied by repetitivc firings are observed in hippocampal CA3 pyramidal neurons of NER with seizures. Using hippocampal slice preparations of NER, the present electrophysiologi- cal study was performed to elucidate whether this abnormal firing in CA3 neurons developed with age and if abnormality of Ca2+ channel was involved. Methods: Hippocampal slices (40Opm) werc prepared from NER and normal Wistar rats (age; 4,29 weeks). A single rectangular pulse stimulus composed of 0.1-ms duration was delivered to the mossy fibers every 5 seconds though a bipolar electrode placed in the granular cell layer of the dentate gyrus. Intracellular recording was made from the CA3 pyramidal cell using a microelectrode containing 3M KCI intracellular recordings. A Ca2+ spike was elicited by applying a depolarizing pulse (InA, 120ms) in the cell through the recording electrode under a blockadc of Na+ and K+ channels using 1 pM tetrodotoxin and I 0mM tctraethylammonium added to the artificial CSF, respectivcly. Nicardipine (I-IOOnM), a Ca2+ channel blocker, was applicd to the bath. Results: Thirty-seven slices from I9 NER and 6 slices from 4 normal Wishe rats were used. There were no obvious changes in the resting membrane potentials of CA3 neurons between NER and Wistar rats tested. When a single stimulus was delivered to the mossy fibers, a long-lasting depolarization shift accompanied by repetitive firings followed by after-hyperpolarization werc also obtained i n hippocampal CA3 neurons of young NER (4,5 weeks of age) before occurrence of any seizurcs, although the depolarization shift in younger NER was shorter than that in NER aged more than 6 weeks. These abnormal firings werc evokcd in 58% and 30% of all CA3 neurons tested in the younger and mature NER (6,1 5 weeks of age), respectively. Furthermore, abnormal firing was not elicited in NER aged after I6 weeks. Agc-matched Wistar rats showed only single action potentials without any depolarization shift with single mossy fiber stimulation. Bath application of nicardipine (IOnM) inhibited this long-lasting depolarization shift and the accompanying repetitive firing followed by afterhypcrpolarization without affecting the first spike induced by mossy fiber stimulations. Furthermore, nicai-dipine (IOnM) inhibited the Ca2+ spikes elicited by applying a depolarizing pulse in the neurons of NER with seizures, although a higher dose (100nM) did not affect those in Wistar rats. Conclusions: These findings indicate that abnormal excitability of the NER CA3 pyramidal neurons is probably due to abnormality in the Ca2+ channcls. The abnorinal excitability was observed in NER at an age when tonic-clonic convulsions were not detected, suggesting that thc hippocampus may probably scrve as an epileptogenic focus in younger NER and the seizure impulses originating i n this area are transinittcd to the new other seizurc foci in mature NER. [source]

    The Anticonvulsant SGB-017 (ADCI) Blocks Voltage-Gated Sodium Channels in Rat and Human Neurons: Comparison with Carbamazepine

    EPILEPSIA, Issue 3 2000
    Lucy Sun
    Summary: Purpose: SGB-017 (ADCI) is a novel anticonvul-sant that blocks both voltage-activated sodium channels and N -methyl- d -aspartate (NMDA)-receptor-gated channels. Results by Rogawski et al. suggested that SGB-017 produces its anticonvulsant action primarily by inhibition of NMDA-receptor channels. However, SGB-017 is effective in several animal models of epilepsy that are unresponsive to NMDA antagonists. These results indicate that block of NMDA-receptor channels is not the only mechanism contributing to its anticonvulsant activity. Thus the effects of SGB-017 on neu-ronal sodium channels were investigated. Methods: Whole cell voltage-clamp techniques were used to record sodium currents in freshly dissociated rat superior cervical ganglion (SCG) and hippocampal neurons and cultured human NT2 neurons. The effects of SGB-017 on the amplitude of sodium currents, elicited by a depolarizing pulse to 0 mV from different holding potentials, were measured and compared with those of carbamazepine (CBZ). Results: SGB-017 inhibited sodium currents in rat SCG and hippocampal neurons with a similar potency to CBZ. Like CBZ, the inhibition of sodium channels by SGB-017 was voltage dependent. Its median inhibitory concentration (IC50) for inhibition of sodium channels at depolarized holding potentials is similar to that for its inhibition of NMDA receptor channels. In human hNT2 neurons, SGB-017 was more potent than CBZ at inhibiting sodium currents. Conclusions: SGB-017 produces its anticonvulsant activity by blocking both sodium- and NMDA-receptor channels in a voltage- and use-dependent manner. The combination of these two mechanisms of action makes SGB-017 an effective AED in several different animal models of epilepsy. [source]

    Neuronal disinhibition in the trigeminal nucleus caudalis in a model of chronic neuropathic pain

    Yasmina B. Martin
    Abstract The mechanisms underlying neuropathic facial pain syndromes are incompletely understood. We used a unilateral chronic constriction injury of the rat infraorbital nerve (CCI-IoN) as a facial neuropathic model. Pain-related behavior of the CCI-IoN animals was tested at 8, 15 and 26 days after surgery (dps). The response threshold to mechanical stimulation with von Frey hairs on the injured side was reduced at 15 and 26 dps, indicating the presence of allodynia. We performed unitary recordings in the caudalis division of the spinal trigeminal nucleus (Sp5C) at 8 or 26 dps, and examined spontaneous activity and responses to mechanical and thermal stimulation of the vibrissal pad. Neurons were identified as wide dynamic range (WDR) or low-threshold mechanoreceptive (LTM) according to their response to tactile and/or noxious stimulation. Following CCI-IoN, WDR neurons, but not LTM neurons, increased their spontaneous activity at 8 and 26 dps, and both types of Sp5C neurons increased their responses to tactile stimuli. In addition, the on,off tactile response in neurons recorded after CCI-IoN was followed by afterdischarges that were not observed in control cases. Compared with controls, the response inhibition observed during paired-pulse stimulation was reduced after CCI-IoN. Immunohistochemical studies showed an overall decrease in GAD65 immunoreactivity in Sp5C at 26 dps, most marked in laminae I and II, suggesting that following CCI-IoN the inhibitory circuits in the sensory trigeminal nuclei are depressed. Consequently, our results strongly suggest that disinhibition of Sp5C neurons plays a relevant role in the appearance of allodynia after CCI-IoN. [source]

    Neurons in primary motor cortex engaged during action observation

    Juliana Dushanova
    Abstract Neurons in higher cortical areas appear to become active during action observation, either by mirroring observed actions (termed mirror neurons) or by eliciting mental rehearsal of observed motor acts. We report the existence of neurons in the primary motor cortex (M1), an area that is generally considered to initiate and guide movement performance, responding to viewed actions. Multielectrode recordings in monkeys performing or observing a well-learned step-tracking task showed that approximately half of the M1 neurons that were active when monkeys performed the task were also active when they observed the action being performed by a human. These ,view' neurons were spatially intermingled with ,do' neurons, which are active only during movement performance. Simultaneously recorded ,view' neurons comprised two groups: approximately 38% retained the same preferred direction (PD) and timing during performance and viewing, and the remainder (62%) changed their PDs and time lag during viewing as compared with performance. Nevertheless, population activity during viewing was sufficient to predict the direction and trajectory of viewed movements as action unfolded, although less accurately than during performance. ,View' neurons became less active and contained poorer representations of action when only subcomponents of the task were being viewed. M1 ,view' neurons thus appear to reflect aspects of a learned movement when observed in others, and form part of a broadly engaged set of cortical areas routinely responding to learned behaviors. These findings suggest that viewing a learned action elicits replay of aspects of M1 activity needed to perform the observed action, and could additionally reflect processing related to understanding, learning or mentally rehearsing action. [source]

    Overexpression of GAP-43 modifies the distribution of the receptors for myelin-associated growth-inhibitory proteins in injured Purkinje axons

    Simona Foscarin
    Abstract Neurons with enhanced intrinsic growth capabilities can elongate their axons into non-permissive territories, but the mechanisms that enable the outgrowing processes to overcome environmental inhibition are largely unknown. To address this issue, we examined adult mouse Purkinje cells that overexpress the axonal growth-associated protein GAP-43. After injury, these neurons exhibit sprouting along the intracortical neuritic course and at the severed stump in the white matter. To determine whether GAP-43-overexpressing Purkinje cells are responsive to extrinsic inhibitory cues, we investigated the content and subcellular localization of major receptors for myelin-associated inhibitory proteins, PlexinB1 and the Nogo receptor (NgR) with the related co-receptors LINGO-1 and p75. Expression of these molecules, estimated by measuring perikaryal immunostaining intensity and Western blot, was not different in wild-type or transgenic mice, and it was not overtly modified after axotomy. Following injury, however, the content of PlexinB1 was significantly reduced in GAP-43-overexpressing neurites. Furthermore, in the same axons the distribution of both PlexinB1 and NgR was altered, being inverse to that of GAP-43. Labelling for the two receptors was conspicuously reduced on the axonal surface and it was almost undetectable in the outgrowing sprouts, which showed strong GAP-43 immunoreactivity. These observations indicate that although GAP-43 overexpression does not modify the expression of receptors for myelin-associated inhibitory factors, it interferes with their subcellular localization and exposure on the neuritic membrane. Therefore, GAP-43 promotes axon growth by multiple synergistic mechanisms that potentiate the intrinsic motility of the elongating processes, while reducing their sensitivity to environmental inhibition. [source]

    Comparison of spatial integration and surround suppression characteristics in spiking activity and the local field potential in macaque V1

    M. A. Gieselmann
    Abstract Neurons in primary visual cortex exhibit well documented centre,surround receptive field organization, whereby the centre is dominated by excitatory influences and the surround is generally dominated by inhibitory influences. These effects have largely been established by measuring the output of neurons, i.e. their spiking activity. How excitation and inhibition are reflected in the local field potential (LFP) is little understood. As this can bear on the interpretation of human fMRI BOLD data and on our understanding of the mechanisms of local field potential oscillations, we measured spatial integration and centre,surround properties in single- and multiunit recordings of V1 in the awake fixating macaque monkey, and compared these to spectral power in different frequency bands of simultaneously recorded LFPs. We quantified centre,surround organization by determining the size of the summation and suppression area in spiking activity as well as in different frequency bands of the LFP, with the main focus on the gamma band. Gratings extending beyond the summation area usually inhibited spiking activity while the LFP gamma-band activity increased monotonically for all grating sizes. This increase was maximal for stimuli infringing upon the near classical receptive field surround, where suppression started to dominate spiking activity. Thus, suppressive influences in primary cortex can be inferred from spiking activity, but they also seem to affect specific features of gamma-band LFP activity. [source]

    Phenotype of V2-derived interneurons and their relationship to the axon guidance molecule EphA4 in the developing mouse spinal cord

    Line Lundfald
    Abstract The ventral spinal cord consists of interneuron groups arising from distinct, genetically defined, progenitor domains along the dorsoventral axis. Many of these interneuron groups settle in the ventral spinal cord which, in mammals, contains the central pattern generator for locomotion. In order to better understand the locomotor networks, we have used different transgenic mice for anatomical characterization of one of these interneuron groups, called V2 interneurons. Neurons in this group are either V2a interneurons marked by the postmitotic expression of the transcription factor Chx10, or V2b interneurons which express the transcription factors Gata2 and Gata3. We found that all V2a and most V2b interneurons were ipsilaterally projecting in embryos as well as in newborns. V2a interneurons were for the most part glutamatergic while V2b interneurons were mainly GABAergic or glycinergic. Furthermore, we demonstrated that a large proportion of V2 interneurons expressed the axon guidance molecule EphA4, a molecule previously shown to be important for correct organization of locomotor networks. We also showed that V2 interneurons and motor neurons alone did not account for all EphA4-expressing neurons in the spinal cord. Together, these findings enable a better interpretation of neural networks underlying locomotion, and open up the search for as yet unknown components of the mammalian central pattern generator. [source]

    GABAergic projections from the hippocampus to the retrosplenial cortex in the rat

    Toshio Miyashita
    Abstract The retrosplenial cortex (RS) in rats has been implicated in a wide range of behaviors, including spatial navigation and memory. Relevant to this, the RS is closely interconnected with the hippocampus by multiple direct and indirect routes. Here, by injecting the retrograde tracer cholera toxin subunit B conjugated with Alexa488 (CTB-Alexa488) in the granular retrosplenial cortex (GRS), we demonstrate a moderately dense non-pyramidal projection from CA1. Neurons are in several layers, but mainly (about 65%) at the border of the stratum radiatum (SR) and stratum lacunosum moleculare (SLM). In particular, by double-labeling with GAD67 or ,-aminobutyric acid (GABA), we establish that these neurons are GABAergic. Further immunocytochemical screening for calcium-binding proteins, somatostatin (SS) or cholecystokinin (CCK) failed to identify additional neurochemical subgroups; but a small subset (about 14%) is positive for the m2 muscarinic acetylcholine receptor (M2R). Terminations target layer 1 of the GRS, as shown by biotinylated dextran amine (BDA) injections into CA1 and confirmed by a very superficial injection of CTB-Alexa488 in GRS. The superficial injection shows that there is a sparse GABAergic projection from the subiculum to layer 1 of the GRS, in addition to the dense excitatory connections to layer 3. The role of these dual inhibitory,excitatory pathways , within the subiculum, and in parallel from CA1 and the subiculum , remains to be determined, but may be related to synchronized oscillatory activity in the hippocampal complex and GRS, or to the generation of rhythmic activity within the GRS. [source]

    Muscarine activates the sodium,calcium exchanger via M3 receptors in basal forebrain neurons

    Changqing Xu
    Abstract Neurons of the medial septum/diagonal band of Broca (MSDB) project to the hippocampus. Muscarinic cholinergic mechanisms within the MSDB are potent modulators of hippocampal functions; intraseptal scopolamine disrupts and intraseptal carbachol facilitates hippocampus-dependent learning and memory tasks, and the associated hippocampal theta rhythm. In earlier work, we demonstrated that, within the MSDB, the septohippocampal GABAergic but not cholinergic neurons are the primary target of muscarinic manipulations and that muscarinic activation of septohippocampal GABAergic neurons is mediated directly via M3 receptors. In the present study, we examined the ionic mechanism(s) underlying the excitatory actions of muscarine in these neurons. Using whole-cell patch-clamp recording techniques in rat brain slices, we demonstrated that M3 receptor-mediated muscarinic activation of MSDB neurons is dependent on external Na+ and is also reduced by bath-applied Ni2+ and KB-R7943 as well as by replacing external Na+ with Li+, suggesting a primary involvement of the Na+,Ca2+ exchanger. We conclude that the M3 receptor-mediated muscarinic activation of MSDB septohippocampal GABA-type neurons, that is important for cognitive functioning, is mediated via activation of the Na+,Ca2+ exchanger. [source]

    Immunolocalization of BK channels in hippocampal pyramidal neurons

    Claudia A. Sailer
    Abstract Neurons are highly specialized cells in which the integration and processing of electrical signals critically depends on the precise localization of ion channels. For large-conductance Ca2+ - activated K+ (BK) channels, targeting to presynaptic membranes in hippocampal pyramidal cells was reported; however, functional evidence also suggests a somatodendritic localization. Therefore we re-examined the subcellular distribution of BK channels in mouse hippocampus using a panel of independent antibodies in a combined approach of conventional immunocytochemistry on cultured neurons, pre- and postembedding electron microscopy and immunoprecipitation. In cultured murine hippocampal neurons, the colocalization of BK channels with both pre- and postsynaptic marker proteins was observed. Electron microscopy confirmed targeting of BK channels to axonal as well as dendritic membranes of glutamatergic synapses in hippocampus. A postsynaptic localization of BK channels was also supported by the finding that the channel coimmunoprecipitated with PSD95, a protein solely expressed in the postsynaptic compartment. These results thus demonstrate that BK channels reside in both post- and presynaptic compartments of hippocampal pyramidal neurons. [source]

    Disparate cholinergic currents in rat principal trigeminal sensory nucleus neurons mediated by M1 and M2 receptors: a possible mechanism for selective gating of afferent sensory neurotransmission

    Kristi A. Kohlmeier
    Abstract Neurons situated in the principal sensory trigeminal nucleus (PSTN) convey orofacial sensory inputs to thalamic relay regions and higher brain centres, and the excitability of these ascending tract cells is modulated across sleep/wakefulness states and during pain conditions. Moreover, acetylcholine release changes profoundly across sleep/wakefulness states and ascending sensory neurotransmission is altered by cholinergic agonists. An intriguing possibility is, therefore, that cholinergic mechanisms mediate such state-dependent modulation of PSTN tract neurons. We tested the hypotheses that cholinergic agonists can modulate PSTN cell excitability and that such effects are mediated by muscarinic receptor subtypes, using patch-clamp methods in rat and mouse. In all examined cells, carbachol elicited an electrophysiological response that was independent of action potential generation as it persisted in the presence of tetrodotoxin. Responses were of three types: depolarization, hyperpolarization or a biphasic response consisting of hyperpolarization followed by depolarization. In voltage-clamp mode, carbachol evoked corresponding inward, outward or biphasic currents. Moreover, immunostaining for the vesicle-associated choline transporter showed cholinergic innervation of the PSTN. Using muscarinic receptor antagonists, we found that carbachol-elicited PSTN neuron hyperpolarization was mediated by M2 receptors and depolarization, in large part, by M1 receptors. These data suggest that acetylcholine acting on M1 and M2 receptors may contribute to selective excitability enhancement or depression in individual, rostrally projecting sensory neurons. Such selective gating effects via cholinergic input may play a functional role in modulation of ascending sensory transmission, including across behavioral states typified by distinct cholinergic tone, e.g. sleep/wakefulness arousal levels or neuropathic pain conditions. [source]

    Ventral pallidal neurons code incentive motivation: amplification by mesolimbic sensitization and amphetamine

    Amy J. Tindell
    Abstract Neurons in ventral pallidum fire to reward and its predictive cues. We tested mesolimbic activation effects on neural reward coding. Rats learned that a Pavlovian conditioned stimulus (CS+1 tone) predicted a second conditioned stimulus (CS+2 feeder click) followed by an unconditioned stimulus (UCS sucrose reward). Some rats were sensitized to amphetamine after training. Electrophysiological activity of ventral pallidal neurons to stimuli was later recorded under the influence of vehicle or acute amphetamine injection. Both sensitization and acute amphetamine increased ventral pallidum firing at CS+2 (population code and rate code). There were no changes at CS+1 and minimal changes to UCS. With a new ,Profile Analysis', we show that mesolimbic activation by sensitization/amphetamine incrementally shifted neuronal firing profiles away from prediction signal coding (maximal at CS+1) and toward incentive coding (maximal at CS+2), without changing hedonic impact coding (maximal at UCS). This pattern suggests mesolimbic activation specifically amplifies a motivational transform of CS+ predictive information into incentive salience coded by ventral pallidal neurons. Our results support incentive-sensitization predictions and suggest why cues temporally proximal to drug presentation may precipitate cue-triggered relapse in human addicts. [source]

    Translation of an integral membrane protein in distal dendrites of hippocampal neurons

    Jeffrey C. Grigston
    Abstract Maintenance of synaptic plasticity requires protein translation. Because changes in synaptic strength are regulated at the level of individual synapses, a mechanism is required for newly translated proteins to specifically and persistently modify only a subset of synapses. Evidence suggests this may be accomplished through local translation of proteins at or near synapses in response to plasticity-inducing patterns of activity. A number of proteins important for synaptic function are integral membrane proteins, which require a specialized group of organelles, proteins and enzymatic activities for proper synthesis. Dendrites appear to contain machinery necessary for the proper production of these proteins, and mRNAs for integral membrane proteins have been found localized to dendrites. Experiments are described that investigate the local translation of membrane proteins in the dendrites of cultured rat hippocampal neurons, using fluorescence recovery after photobleaching. Neurons were transfected with cDNAs encoding a fluorescently labeled transmembrane protein, TGN-38. Under conditions where the transport of this reporter construct was inhibited, the appearance of newly synthesized protein was observed via fluorescent microscopy. The dendritic translation of this protein required activation of glutamate receptors. The results demonstrate a functional capacity for activity-dependent synthesis of integral membrane proteins for distal dendrites in hippocampal neurons. [source]

    The actin-binding protein profilin I is localized at synaptic sites in an activity-regulated manner

    Henrike Neuhoff
    Abstract Morphological changes at synaptic specializations have been implicated in regulating synaptic strength. Actin turnover at dendritic spines is regulated by neuronal activity and contributes to spine size, shape and motility. The reorganization of actin filaments requires profilins, which stimulate actin polymerization. Neurons express two independent gene products , profilin I and profilin II. A role for profilin II in activity-dependent mechanisms at spine synapses has recently been described. Although profilin I interacts with synaptic proteins, little is known about its cellular and subcellular localization in neurons. Here, we investigated the subcellular distribution of this protein in brain neurons as well as in hippocampal cultures. Our results indicate that the expression of profilin I varies in different brain regions. Thus, in cerebral cortex and hippocampus profilin I immunostaining was associated predominantly with dendrites and was present in a subset of dendritic spines. In contrast, profilin I in cerebellum was associated primarily with presynaptic structures. Profilin I immunoreactivity was partially colocalized with the synaptic molecules synaptophysin, PSD-95 and gephyrin in cultured hippocampal neurons, indicating that profilin I is present in only a subset of synapses. At dendritic spine structures, profilin I was found primarily in protrusions, which were in apposition to presynaptic terminal boutons. Remarkably, depolarization with KCl caused a moderate but significant increase in the number of synapses containing profilin I. These results show that profilin I can be present at both pre- and postsynaptic sites and suggest a role for this actin-binding protein in activity-dependent remodelling of synaptic structure. [source]