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Synaptic Connections (synaptic + connection)
Selected AbstractsSynaptic connections of cholinergic antennal lobe relay neurons innervating the lateral horn neuropile in the brain of Drosophila melanogasterTHE JOURNAL OF COMPARATIVE NEUROLOGY, Issue 3 2003Kouji Yasuyama Abstract Presumed cholinergic projection neurons (PNs) in the brain of the fruit fly Drosophila melanogaster, immunoreactive to choline acetyltransferase (ChAT), convey olfactory information between the primary sensory antennal lobe neuropile and the mushroom body calyces, and finally terminate in the lateral horn (LH) neuropile. The texture and synaptic connections of ChAT PNs in the LH and, comparatively, in the smaller mushroom body calyces were investigated by immuno light and electron microscopy. The ChAT PN fibers of the massive inner antennocerebral tract (iACT) extend into all portions of the LH, distributing in a nonrandom fashion. Immunoreactive boutons accumulate in the lateral margins of the LH, whereas the more proximal LH exhibits less intense immunolabeling. Boutons with divergent presynaptic sites, unlabeled as well as ChAT-immunoreactive, appear to be the preponderant mode of synaptic input throughout the LH. Synapses of ChAT-labeled fibers appear predominantly as divergent synaptic boutons (diameters 1,3 ,m), connected to unlabeled postsynaptic profiles, or alternatively as a minority of tiny postsynaptic spines (diameters 0.05,0.5 ,m) among unlabeled profiles. Together these spines encircle unidentified presynaptic boutons of interneurons which occupy large areas of the LH. Thus, synaptic circuits in the LH differ profoundly from those of the PNs in the mushroom body calyx, where ChAT spines have not been encountered. Synaptic contacts between LH ChAT elements were not observed. The synaptic LH neuropile may serve as an output area for terminals of the ChAT PNs, their presynaptic boutons providing input to noncholinergic relay neurons. The significance of the postsynaptic neurites of the ChAT PNs is discussed; either local or other interneurons might connect the ChAT PNs within the LH, or PNs might receive inputs arising from outside the LH. J. Comp. Neurol. 466:299,315, 2003. © 2003 Wiley-Liss, Inc. [source] Synaptic plasticity and functionality at the cone terminal of the developing zebrafish retinaDEVELOPMENTAL NEUROBIOLOGY, Issue 3 2003Oliver Biehlmaier Abstract Previous studies have analyzed photoreceptor development, some inner retina cell types, and specific neurotransmitters in the zebrafish retina. However, only minor attention has been paid to the morphology of the synaptic connection between photoreceptors and second order neurons even though it represents the transition from the light sensitive receptor to the neuronal network of the visual system. Here, we describe the appearance and differentiation of pre- and postsynaptic elements at cone synapses in the developing zebrafish retina together with the maturation of the directly connecting second order neurons and a dopaminergic third order feedback-neuron from the inner retina. Zebrafish larvae were examined at developmental stages from 2 to 7dpf (days postfertilization) and in the adult. Synaptic maturation at the photoreceptor terminals was examined with antibodies against synapse associated proteins. The appearance of synaptic plasticity at the so-called spinule-type synapses between cones and horizontal cells was assessed by electron microscopy, and the maturation of photoreceptor downstream connection was identified by immunocytochemistry for GluR4 (AMPA-type glutamate receptor subunit), protein kinase ,1 (mixed rod-cone bipolar cells), and tyrosine hydroxylase (dopaminergic interplexiform cells). We found that developing zebrafish retinas possess first synaptic structures at the cone terminal as early as 3.5dpf. Morphological maturation of these synapses at 3.5,4dpf, together with the presence of synapse associated proteins at 2.5dpf and the maturation of second order neurons by 5dpf, indicate functional synaptic connectivity and plasticity between the cones and their second order neurons already at 5dpf. However, the mere number of spinules and ribbons at 7dpf still remains below the adult values, indicating that synaptic functionality of the zebrafish retina is not entirely completed at this stage of development. © 2003 Wiley Periodicals, Inc. J Neurobiol 56: 222,236, 2003 [source] How does the brain learn language?DEVELOPMENTAL MEDICINE & CHILD NEUROLOGY, Issue 2 2000Insights from the study of children with, without language impairment Neurobiological studies have generated new ways of thinking about development of brain structure and function. Development involves more than just growth from simple to complex structures. The initial over-abundance of neurons and synaptic connections is subsequently pruned of those that are non-functional. In addition, as behavioural and cognitive functions emerge and become automatized, the underlying brain representations are reorganized. In this paper, I shall argue that these different modes of neurodevelopmental change provide a useful metaphor for examining language acquisition. It will be argued that language acquisition can involve learning to ignore and inhibit irrelevant information, as well as forming new ways of representing complex information economically. Modular organization is not present from the outset, but develops gradually. This analysis suggests a new way of assessing specific language impairment (SLI). There has been much debate as to whether children with SLI lack specific modular components of a language processing system. I propose instead that these children persist in using inefficient ways of representing language. Finally, I consider what we know about the neurobiological basis of such a deficit. There is mounting evidence that children with SLI have subtle structural anomalies affecting the language areas of the brain, which are largely genetically determined. We should not, however, conclude that the language difficulties are immutable. [source] Brain-derived neurotrophic factor and the development of structural neuronal connectivityDEVELOPMENTAL NEUROBIOLOGY, Issue 5 2010Susana Cohen-Cory Abstract During development, neural networks are established in a highly organized manner, which persists throughout life. Neurotrophins play crucial roles in the developing nervous system. Among the neurotrophins, brain-derived neurotrophic factor (BDNF) is highly conserved in gene structure and function during vertebrate evolution, and serves an important role during brain development and in synaptic plasticity. BDNF participates in the formation of appropriate synaptic connections in the brain, and disruptions in this process contribute to disorders of cognitive function. In this review, we first briefly highlight current knowledge on the expression, regulation, and secretion of BDNF. Further, we provide an overview of the possible actions of BDNF in the development of neural circuits, with an emphasis on presynaptic actions of BDNF during the structural development of central neurons. © 2010 Wiley Periodicals, Inc. Develop Neurobiol 2010 [source] Characterization of dendritic spines in the Drosophila central nervous systemDEVELOPMENTAL NEUROBIOLOGY, Issue 4 2009Florian Leiss Abstract Dendritic spines are a characteristic feature of a number of neurons in the vertebrate nervous system and have been implicated in processes that include learning and memory. In spite of this, there has been no comprehensive analysis of the presence of spines in a classical genetic system, such as Drosophila, so far. Here, we demonstrate that a subset of processes along the dendrites of visual system interneurons in the adult fly central nervous system, called LPTCs, closely resemble vertebrate spines, based on a number of criteria. First, the morphology, size, and density of these processes are very similar to those of vertebrate spines. Second, they are enriched in actin and devoid of tubulin. Third, they are sites of synaptic connections based on confocal and electron microscopy. Importantly, they represent a preferential site of localization of an acetylcholine receptor subunit, suggesting that they are sites of excitatory synaptic input. Finally, their number is modulated by the level of the small GTPase dRac1. Our results provide a basis to dissect the genetics of dendritic spine formation and maintenance and the functional role of spines. © 2009 Wiley Periodicals, Inc. Develop Neurobiol, 2009 [source] Adaptation of microglomerular complexes in the honeybee mushroom body lip to manipulations of behavioral maturation and sensory experienceDEVELOPMENTAL NEUROBIOLOGY, Issue 8 2008Sabine Krofczik Abstract Worker honeybees proceed through a sequence of tasks, passing from hive and guard duties to foraging activities. The underlying neuronal changes accompanying and possibly mediating these behavioral transitions are not well understood. We studied changes in the microglomerular organization of the mushroom bodies, a brain region involved in sensory integration, learning, and memory, during adult maturation. We visualized the MB lips' microglomerular organization by applying double labeling of presynaptic projection neuron boutons and postsynaptic Kenyon cell spines, which form microglomerular complexes. Their number and density, as well as the bouton volume, were measured using 3D-based techniques. Our results show that the number of microglomerular complexes and the bouton volumes increased during maturation, independent of environmental conditions. In contrast, manipulations of behavior and sensory experience caused a decrease in the number of microglomerular complexes, but an increase in bouton volume. This may indicate an outgrowth of synaptic connections within the MB lips during honeybee maturation. Moreover, manipulations of behavioral and sensory experience led to adaptive changes, which indicate that the microglomerular organization of the MB lips is not static and determined by maturation, but rather that their organization is plastic, enabling the brain to retain its synaptic efficacy. © 2008 Wiley Periodicals, Inc. Develop Neurobiol, 2008. [source] Tonotopic gradients of Eph family proteins in the chick nucleus laminaris during synaptogenesisDEVELOPMENTAL NEUROBIOLOGY, Issue 1 2004Abigail L. Person Abstract Topographically precise projections are established early in neural development. One such topographically organized network is the auditory brainstem. In the chick, the auditory nerve transmits auditory information from the cochlea to nucleus magnocellularis (NM). NM in turn innervates nucleus laminaris (NL) bilaterally. These projections preserve the tonotopy established at the level of the cochlea. We have begun to examine the expression of Eph family proteins during the formation of these connections. Optical density measurements were used to describe gradients of Eph proteins along the tonotopic axis of NL in the neuropil, the somata, and the NM axons innervating NL at embryonic day 10, when synaptic connections from NM to NL are established. At E10,11, NL dorsal neuropil expresses EphA4 at a higher concentration in regions encoding high frequency sounds, decreasing in concentration monotonically toward the low frequency (caudolateral) end. In the somata, both EphA4 and ephrin-B2 are concentrated at the high frequency end of the nucleus. These tonotopic gradients disappear between E13 and E15, and expression of these molecules is completely downregulated by hatching. The E10,11 patterns run counter to an apparent gradient in dendrite density, as indicated by microtubule associated protein 2 (MAP2) immunolabeling. Finally, ephrin-B2 is also expressed in a gradient in tissue ventral to the NL neuropil. Our findings thus suggest a possible conserved mechanism for establishing topographic projections in diverse sensory systems. These results of this study provide a basis for the functional examination of the role of Eph proteins in the formation of tonotopic maps in the brainstem. © 2004 Wiley Periodicals, Inc. J Neurobiol 60: 28,39, 2004 [source] The heterogeneous distribution of functional synaptic connections in rat hippocampal dissociated neuron culturesELECTRONICS & COMMUNICATIONS IN JAPAN, Issue 6 2009Suguru N. Kudoh Abstract The dynamics of functional synaptic connections are critical for information processing systems in the brain, such as perception and learning. Using rat hippocampal cells cultured on multielectrode arrays, we investigated the spatiotemporal pattern of spontaneous action potentials. The neurons developed connections and a characteristic high-frequency bursting (HFB) activity was observed transiently. After the period of HFB activity, the distribution of spontaneous activity changed drastically with the appearance of neurons with frequent electrical activity and neurons with little activity in the network. The functional connections of all the combinations of recorded spike trains were estimated and depicted simultaneously in a Connection Map. This map revealed that each culture contained hublike neurons with many functional connections, suggesting that the cultures of dissociated rat hippocampal neurons on multielectrode arrays formed heterogeneous networks of functional connections. In addition, the functional connections were drastically reorganized after the induction of synaptic potentiation, and novel hub neurons emerged. These results indicate that spontaneous activity is enough to construct dynamic assemblies of neurons connected to each other by functional synaptic connections, and that synaptic potentiation can induce reorganization of such assemblies of neurons. © 2009 Wiley Periodicals, Inc. Electron Comm Jpn, 92(6): 41,49, 2009; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecj.10063 [source] Embryonic striatal grafts restore bi-directional synaptic plasticity in a rodent model of Huntington's diseaseEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 11 2009David Mazzocchi-Jones Abstract Embryonic striatal grafts integrate with the host striatal circuitry, forming anatomically appropriate connections capable of influencing host behaviour. In addition, striatal grafts can influence host behaviour via a variety of non-specific, trophic and pharmacological mechanisms; however, direct evidence that recovery is dependent on circuit reconstruction is lacking. Recent studies suggest that striatal grafts alleviate simple motor deficits, and also that learning of complex motor skills and habits can also be restored. However, although the data suggest that such ,re-learning' requires integration of the graft into the host striatal circuitry, little evidence exists to demonstrate that such integration includes functional synaptic connections. Here we demonstrate that embryonic striatal grafts form functional connections with the host striatal circuitry, capable of restoring stable synaptic transmission, within an excitotoxic lesion model of Huntington's disease. Furthermore, such ,functional integration' of the striatal graft enables the expression of host,graft bi-directional synaptic plasticity, similar to the normal cortico-striatal circuit. These results indicate that striatal grafts express synaptic correlates of learning, and thereby provide direct evidence of functional neuronal circuit repair, an essential component of ,functional integration'. [source] The maintenance of specific aspects of neuronal function and behavior is dependent on programmed cell death of adult-generated neurons in the dentate gyrusEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 7 2009Woon Ryoung Kim Abstract A considerable number of new neurons are generated daily in the dentate gyrus (DG) of the adult hippocampus, but only a subset of these survive, as many adult-generated neurons undergo programmed cell death (PCD). However, the significance of PCD in the adult brain for the functionality of DG circuits is not known. Here, we examined the electrophysiological and behavioral characteristics of Bax -knockout (Bax -KO) mice in which PCD of post-mitotic neurons is prevented. The continuous increase in DG cell numbers in Bax -KO mice resulted in the readjustment of afferent and efferent synaptic connections, represented by age-dependent reductions in the dendritic arborization of DG neurons and in the synaptic contact ratio of mossy fibers with CA3 dendritic spines. These neuroanatomical changes were associated with reductions in synaptic transmission and reduced performance in a contextual fear memory task in 6-month-old Bax -KO mice. These results suggest that the elimination of excess DG neurons via Bax -dependent PCD in the adult brain is required for the normal organization and function of the hippocampus. [source] Glutamate regulates retinal progenitors cells proliferation during developmentEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 4 2006Rodrigo A. P. Martins Abstract The precise coordination of cell cycle exit and cell fate specification is essential for generating the correct proportion of retinal cell types during development. The decision to exit the cell cycle is regulated by intrinsic and extrinsic cues. There is growing evidence that neurotransmitters can regulate cell proliferation and cell fate specification during the early stages of CNS development prior to the formation of synaptic connections. We found that the excitatory neurotransmitter glutamate regulates retinal progenitor cell proliferation during embryonic development of the mouse. AMPA/kainate and N -methyl- d -aspartate receptors are expressed in embryonic retinal progenitor cells. Addition of exogenous glutamate leads to a dose-dependent decrease in cell proliferation without inducing cell death or activating the p53 pathway. Activation of AMPA/kainate receptors induced retinal progenitor cells to prematurely exit the cell cycle. Using a replication-incompetent retrovirus to follow the clonal expansion of individual retinal progenitor cells, it was observed that blockade of AMPA/kainate receptors increased the proportion of large clones, showing that modulation of endogenous glutamatergic activity can have long-term consequences on retinal cell proliferation. Real time reverse transcriptase-polymerase chain reaction and immunoblot analyses demonstrated that glutamate does not alter the levels of the mRNA and proteins that regulate the G1/S-phase transition. Instead, the activity of the Cdk2 kinase is reduced in the presence of glutamate. These data indicate that glutamate regulates retinal progenitor cell proliferation by post-translational modulation of cyclin/Cdk2 kinase activity. [source] In vivo optical recordings of synaptic transmission and intracellular Ca2+ and Cl, in the superior colliculus of fetal ratsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 6 2006Yoshiyuki Sakata Abstract Although the N -methyl- d -aspartate (NMDA) receptor is known to play a crucial role in activity-dependent remodeling of synaptic connections in the fetal superior colliculus (SC), its contribution to the electrical activity of fetal SC neurons has not been determined. Furthermore, whether ,-aminobutyric acid (GABA)-mediated inhibition occurs either as early as prenatal periods or only after eye opening has been controversial. We therefore performed optical recordings using voltage-, Ca2+ - and Cl, -sensitive fluorescent dyes to analyse synaptic transmission and changes in intracellular Ca2+ and Cl, in the SC of fetal rats that were still connected with the dams by the umbilical cord. Excitatory and inhibitory responses were evoked by focal SC stimulation. The excitatory synaptic responses are composed of early and late components. The early component was mediated by both non-NMDA and NMDA receptors, whereas the late component occurred mainly via NMDA receptors. Train pulse stimulation at higher currents was required for induction of the inhibition, which was antagonized by bicuculline, and blocking of the GABA-mediated inhibition by bicuculline uncovered masked excitatory synaptic responses. Focal SC stimulation induced increases in [Cl,]i and [Ca2+]i that were mediated by GABA-A receptors and mainly by NMDA receptors, respectively. GABA antagonists augmented SC-induced increases in [Ca2+]i. These results indicate that, in the fetal SC, excitatory and inhibitory synaptic transmissions occur before birth, that the NMDA receptor is a major contributor to excitatory synaptic transmission and increased [Ca2+]i, and that the GABA-A receptor is already functioning to inhibit excitatory neurotransmission. [source] Differences between the effects of three plasticity inducing protocols on the organization of the human motor cortexEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 3 2006Karin Rosenkranz Abstract Several experimental protocols induce lasting changes in the excitability of motor cortex. Some involve direct cortical stimulation, others activate the somatosensory system and some combine motor and sensory stimulation. The effects usually are measured as changes in amplitude of the motor-evoked-potential (MEP) or short-interval intracortical inhibition (SICI) elicited by a single or paired pulses of transcranial magnetic stimulation (TMS). Recent work has also tested sensorimotor organization within the motor cortex by recording MEPs and SICI during short periods of vibration applied to single intrinsic hand muscles. Here sensorimotor organization is focal: MEPs increase and SICI decreases in the vibrated muscle, whilst the opposite occurs in neighbouring muscles. In six volunteers we compared the after effects of three protocols that lead to lasting changes in cortical excitability: (i) paired associative stimulation (PAS) between a TMS pulse and an electrical stimulus to the median nerve; (ii) motor practice of rapid thumb abduction; and (iii) sensory input produced by semicontinuous muscle vibration, on MEPs and SICI at rest and on the sensorimotor organization. PAS increased MEP amplitudes, whereas vibration changed sensorimotor organization. Motor practice had a dual effect and increased MEPs as well as affecting sensorimotor organization. The implication is that different protocols target different sets of cortical circuits. We speculate that protocols that involve repeated activation of motor cortical output lead to lasting changes in efficacy of synaptic connections in output circuits, whereas protocols that emphasize sensory inputs affect the strength of sensory inputs to motor circuits. [source] Activity-dependent maturation of excitatory synaptic connections in solitary neuron cultures of mouse neocortexEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 2 2005Naoki Takada Abstract Activity plays important roles in the formation and maturation of synaptic connections. We examined these roles using solitary neocortical excitatory neurons, receiving only self-generated synaptic inputs, cultured in a microisland with and without spontaneous spike activity. The amplitude of excitatory postsynaptic currents (EPSCs), evoked by applying brief depolarizing voltage pulses to the cell soma, continued to increase from 7 to 14 days in culture. Short-term depression of EPSCs in response to paired-pulse or 10-train-pulse stimulation decreased with time in culture. These developmental changes were prevented when neurons were cultured in a solution containing tetrodotoxin (TTX). The number of functional synapses estimated by recycled synaptic vesicles with FM4-64 was significantly smaller in TTX-treated than control neurons. However, the miniature EPSC amplitude remained unchanged during development, irrespective of activity. Transmitter release probability, assessed by use-dependent blockade of N -methyl- d -aspartate receptor-mediated EPSCs with MK-801, was higher in TTX-treated than control neurons. Therefore, the activity-dependent increase in EPSC amplitude was mainly ascribed to the increase in synapse number, while activity-dependent alleviation of short-term depression was mostly ascribed to the decrease in release probability. The effect of activity blockade on short-term depression, but not EPSC amplitude, was reversed after 4 days of TTX removal, indicating that synapse number and release probability are controlled by activity in very different ways. These results demonstrate that activity regulates the conversion of immature synapses transmitting low-frequency input signals preferentially to mature synapses transmitting both low- and high-frequency signals effectively, which may be necessary for information processing in mature cortex. [source] Phase-coupled oscillator models can predict hippocampal inhibitory synaptic connectionsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 12 2001F. K. Skinner Abstract What factors are responsible for propagating electrical activity in the hippocampus? Using an intact, isolated hippocampus preparation, it is possible to observe spontaneous delta (, 4 Hz) waves of rhythmic field potentials. These rhythmic potentials are inhibitory in nature, mediated by GABAergic inhibitory potentials originating from a population of principal neurons. They start in the ventro-temporal region and move longitudinally towards the dorso-septal region with a phase lag of , 10% between the extracellular recordings. We use the mathematical framework of phase-coupled oscillators (PCO) to gain some insight into the underlying network system. A chain of 15 nearest-neighbour bidirectionally coupled PCOs is used where each oscillator refers to a segment of the CA1 region of the hippocampus that can generate these slow field potentials. We find that ventro-dorsal delta waves exist if there is a dominance in coupling strength in one direction. Without a one-way coupling dominance, ventro-dorsal waves can still exist, but then the coupling strengths need to be much larger. The relationship between entrained and intrinsic frequencies and the variation of propagation speeds along the longitudinal axis can be used to determine which case applies. Currently available experimental data supports one of the cases, predicting that there is a stronger ventral to dorsal inhibitory effect. [source] Changes in rat hippocampal CA1 synapses following imipramine treatmentHIPPOCAMPUS, Issue 7 2008Fenghua Chen Abstract Neuronal plasticity in hippocampus is hypothesized to play an important role in both the pathophysiology of depressive disorders and the treatment. In this study, we investigated the consequences of imipramine treatment on neuroplasticity (including neurogenesis, synaptogenesis, and remodelling of synapses) in subregions of the hippocampus by quantifying number of neurons and synapses. Adult male Sprague-Dawley rats were injected with imipramine or saline (i.p.) daily for 14 days. Unbiased stereological methods were used to quantify the number of neurons and synapses. No differences in the volume and number of neurons of hippocampal subregions following imipramine treatment were found. However, the number and percentage of CA1 asymmetric spine synapses increased significantly and, conversely, the percentage of asymmetric shaft synapses significantly decreased in the imipramine treated group. Our results indicate that administration of imipramine for 14 days in normal rats could significantly increase the excitatory spine synapses, and change the relative distribution of spine and shaft synapses. We speculate that the present findings may be explained by the establishment of new synaptic connections and by remodelling or transformation of existing synapses. © 2008 Wiley-Liss, Inc. [source] The network behind spatio-temporal patterns: building low-complexity retinal models in CNN based on morphology, pharmacology and physiologyINTERNATIONAL JOURNAL OF CIRCUIT THEORY AND APPLICATIONS, Issue 2 2001Csaba Rekeczky Abstract In this paper, a vertebrate retina model is described based on a cellular neural network (CNN) architecture. Though largely built on the experience of previous studies, the CNN computational framework is considerably simplified: first-order RC cells are used with space-invariant nearest-neighbour interactions only. All non-linear synaptic connections are monotonic continuous functions of the pre-synaptic voltage. Time delays in the interactions are continuous represented by additional first-order cells. The modelling approach is neuromorphic in its spirit relying on both morphological and pharmacological information. However, the primary motivation lies in fitting the spatio-temporal output of the model to the data recorded from biological cells (tiger salamander). In order to meet a low-complexity (VLSI) implementation framework some structural simplifications have been made. Large-neighbourhood interaction (neurons with large processes), furthermore inter-layer signal propagation are modelled through diffusion and wave phenomena. This work presents novel CNN models for the outer and some partial models for the inner (light adapted) retina. It describes an approach that focuses on efficient parameter tuning and also makes it possible to discuss adaptation, sensitivity and robustness issues on retinal ,image processing' from an engineering point of view. Copyright © 2001 John Wiley & Sons, Ltd. [source] Commonalities in the neurobiology between autism and fragile XJOURNAL OF INTELLECTUAL DISABILITY RESEARCH, Issue 10 2008R. Hagerman There is a close association between autism and fragile X syndrome (FXS) with 30% of males with FXS having autism and 2 to 7% of children with autism having the fragile X mutation. The protein that is missing or deficient in FXS, FMRP, is an RNA binding and transport protein which regulates the translation of many messages important for synaptic plasticity. Typically FMRP inhibits the translation of these messages, such that protein production increases when FMRP is absent. Some of these proteins are known to also cause autism when they are mutated including neuroligin 3 and 4 and the SHANK protein. Therefore, when FMRP is missing there is dysregulation of other proteins that are known to cause autism. FMRP is an important inhibitor of protein production in the metabotropic glutamate receptor 5 pathway (mGluR5) which leads to long term depression (LTD) or the weakening of synaptic connections. Therefore, when FMRP is missing there is enhanced mGluR5 activity leading to enhanced LTD and weak or immature synaptic connections. The use of mGluR5 antagonists to reverse the LTD in the animal models of FXS has led to reversal of the learning, behaviour and dendritic spine abnormalities in these animals. There are now initial studies taking place in humans regarding the use of mGluR5 antagonists to improve behaviour and cognition in FXS. It is likely that these mGluR5 antagonists will also be helpful in a subgroup of patients with non fragile X autism who have similar problems with hyperactivity, hyperarousal and anxiety to those seen in FXS. A second cause of autism is the fragile X premutation but this mechanism of involvement is related to RNA toxicity which perhaps stimulates neuroimmune problems and may mimic other causes of autism. Neurons with the premutation are more vulnerable to environmental toxicity and oxidative stress leading to early cell death. [source] Three-dimensional reconstruction and neural map of the serotonergic brain of Asplanchna brightwellii (Rotifera, Monogononta)JOURNAL OF MORPHOLOGY, Issue 4 2009Rick Hochberg Abstract The basic organization of the rotifer brain has been known for nearly a century; yet, fine details on its structure and organization remain limited despite the importance of rotifers in studies of evolution and population biology. To gain insight into the structure of the rotifer brain, and provide a foundation for future neurophysiologic and neurophylogenetic research, the brain of Asplanchna brightwellii was studied with immunohistochemistry, confocal laser scanning microscopy, and computer modeling. A three-dimensional map of serotonergic connections reveals a complex network of approximately 28 mostly unipolar, cerebral perikarya and associated neurites. Cells and their projections display symmetry in quantity, size, connections, and pathways between cerebral hemispheres within and among individuals. Most immunopositive cells are distributed close to the brain midline. Three pairs of neurites form decussations at the brain midline and may innervate sensory receptors in the corona. A single neuronal pathway appears to connect both the lateral horns and dorsolateral apical receptors, suggesting that convergence of synaptic connections may be common in the afferent sensory systems of rotifers. Results show that the neural map of A. brightwellii is much more intricate than that of other monogonont rotifers; nevertheless, the consistency in neural circuits provides opportunities to identify homologous neurons, distinguish functional regions based on neurotransmitter phenotype, and explore new avenues of neurophylogeny in Rotifera. J. Morphol. 2009. © 2008 Wiley-Liss, Inc. [source] Striatal synaptic plasticity: Implications for motor learning and Parkinson's diseaseMOVEMENT DISORDERS, Issue 4 2005Antonio Pisani MD Abstract Changing the strength of synaptic connections between neurons is widely assumed to be the mechanism by which memory traces are encoded and stored in the central nervous system. Plastic changes appear to follow a regional specialization and underlie the specific type of memory mediated by the brain area in which plasticity occurs. Thus, long-term changes occurring at excitatory corticostriatal synapses should be critically involved in motor learning. Indeed, repetitive stimulation of the corticostriatal pathway can cause either a long-lasting increase or an enduring decrease in synaptic strength, respectively referred to as long-term potentiation (LTP), and long-term depression, both requiring a complex sequence of biochemical events. Once established, LTP can be reversed to control levels by a low-frequency stimulation protocol, an active phenomenon defined "synaptic depotentiation," required to erase redundant information. In the 6-hydroxydopamine rat model of Parkinson's disease (PD), striatal synaptic plasticity has been shown to be impaired, although chronic treatment with levodopa was able to restore it. Of interest, a consistent number of L -dopa,treated animals developed involuntary movements, resembling human dyskinesias. Strikingly, electrophysiological recordings from the dyskinetic group of rats demonstrated a selective impairment of synaptic depotentiation. This survey will provide an overview of plastic changes occurring at striatal synapses. The potential relevance of these findings in the control of motor function and in the pathogenesis both of PD and L -dopa,induced motor complications will be discussed. © 2005 Movement Disorder Society [source] Nogo A expression in the adult enteric nervous systemNEUROGASTROENTEROLOGY & MOTILITY, Issue 4 2004S. L. Osborne Abstract, Neuronal plasticity plays an important role in physiological and pathological processes within the gastrointestinal (GI) tract. Nogo A is a major contributor to the negative effect central nervous system (CNS) myelin has on neurite outgrowth after injury and may also play a role in maintaining synaptic connections in the healthy CNS. Nogo A is highly expressed during neuronal development but in the CNS declines postnatally concomitantly with a loss of regenerative potential while ganglia of the Peripheral Nervous System (PNS) retain Nogo A. The enteric nervous system shares a number of features in common with the CNS, thus the peripheral distribution of factors affecting plasticity is of interest. We have investigated the distribution of Nogo in the adult mammalian gastrointestinal tract. Nogo A mRNA and protein are detectable in the adult rat GI tract. Nogo A is expressed heterogeneously in enteric neurons throughout the GI tract though expression levels appear not to be correlated with neuronal sub-type. The pattern of expression is maintained in cultured myenteric plexus from the guinea-pig small intestine. As is seen in developing neurons of the CNS, enteric Nogo A is present in both neuronal cell bodies and axons. Our results point to a hitherto unsuspected role for Nogo A in enteric neuronal physiology. [source] Differential expression of glycans in the hippocampus of rats trained on an inhibitory learning paradigmNEUROPATHOLOGY, Issue 6 2006Alejandra Hidalgo The glycan chains of glycoconjugates play important roles in cell,cell and cell,matrix interactions. In the CNS, previous studies on learning and memory suggest the importance of oligosaccharides attached to glycoconjugates in the modulation of synaptic connections. We studied the hippocampal glycan distribution of rats subject to an inhibitory avoidance task. The expression of glycans was examined by lectin-histochemistry using Vicia villosa lectin (VVL) for terminal ,/, N-acetylgalactosamine (,/, GalNAc); Galanthus nivalus lectin (GNL) for terminal mannose ,-1,3 (Man ,-1,3); Peanut agglutinin (PNA) for galactose ,-1,3N-acetylgalactosamine (Gal ,-1,3 GalNAc); Erythrina cristagalli lectin (ECL) for galactose ,-1,4 N-acetylglucosamine (Gal ,-1,4 GlcNAc); Sambucus nigra lectin (SNA) for sialic acid ,-2.6 galactose (SA ,-2,6 Gal); Maackia amurensis lectin II (MAL II) for sialic acid ,-2,3 (SA ,-2,3); Wheat germ agglutinin (WGA) for terminal N-acetylglucosamine with/without sialic acid (GlcNAc wo SA); succynilated WGA (sWGA) for terminal N-acetylglucosamine without sialic acid (terminal GlcNAc without SA); Griffonia simplicifolia lectin II (GSL II) for terminal ,/, N-acetylglucosamine (,/, GlcNAc terminal); and Lotus tetragonolobus lectin (LTL) ,,fucose. Two groups of 10 animals were examined: non-trained (Control) and Trained rats. ECL, sWGA and GSL II were negative for both groups in all the hippocampal subfields studied. For both groups, VVL was negative in CA4 and granular cells of the Dentate Gyrus (DG) and LTL was negative in the CA4 subfield. Expression of ,/, GalNAc, , -fucose and GlcNAc in other hippocampal subfields was positive, with no differences between groups. However, expression of Man ,-1,3 was significantly higher in the CA1, CA2, CA3, and CA4 subfields in the Trained group. On the other hand, expression of Gal ,-1,3 GalNAc was significantly low in CA4 and DG in the Trained group. In conclusion, the results here presented indicate that the exposure of rats to an associative behavioral paradigm related to declarative memory, involves some regulatory mechanism/s for the differential patterns of glycan expression. [source] Visual deprivation increases accumulation of dense core vesicles in developing optic tectal synapses in Xenopus laevisTHE JOURNAL OF COMPARATIVE NEUROLOGY, Issue 12 2010Jianli Li Abstract Despite considerable progress in understanding the molecular components of synapses in the central nervous system, the ultrastructural rearrangements underlying synaptic development remain unclear. We used serial section transmission electron microscopy and three-dimensional reconstructions of the optic tectal neuropil of Xenopus laevis tadpoles to detect and quantify changes in synaptic ultrastructure over a 1-week period from stages 39 and 47, during which time the visual system of Xenopus tadpoles becomes functional. Synapse density, presynaptic maturation index, and number of synapses per axon bouton increase, whereas the number of DCVs per bouton decreases, between stages 39 and 47. The width of the synaptic cleft decreased and the diameter of postsynaptic profiles increased between stages 39 and 47 and then remained relatively unchanged after stage 47. We found no significant difference in synapse maturation between GABAergic and non-GABAergic synapses. To test the effect of visual experience on synaptogenesis, animals were deprived of visual experience for 3 days from stage 42 to 47. Visual deprivation decreased synapse maturation and the number of connections per bouton. Furthermore, visual deprivation increased the number of DCVs per bouton by more than twofold. The visual-deprivation-induced decrease in synaptic connections is specific to asymmetric non-GABAergic synapses; however, both symmetric GABAergic and asymmetric synapses show comparable increases in the number DCVs with visual deprivation. In both the control and the visually deprived animals, the number of DCVs per bouton is highly variable and does not correlate with either synapse maturation or the number of connected partners per bouton. These data suggest that synaptogenesis and DCV accumulation are regulated by visual experience and further suggest a complex spatial and temporal relation between DCV accumulation and synapse formation. J. Comp. Neurol. 518:2365,2381, 2010. © 2010 Wiley-Liss, Inc. [source] Symmetric synaptic patterns between starburst amacrine cells and direction selective ganglion cells in the rabbit retinaTHE JOURNAL OF COMPARATIVE NEUROLOGY, Issue 1 2008Yung-Cheng Chen Abstract Inputs from starburst amacrine cells (SACs) to ON-OFF direction selective ganglion cells (DSGCs) in the rabbit retina are themselves directional. However, the synaptic asymmetry between SACs and DSGCs required for generating direction selectivity has been controversial. We investigated dendritic contacts and distribution of inhibitory synapses between SACs and their overlapped DSGCs. Double injection of SAC/DSGC pairs and quantitative analysis revealed no obvious asymmetry of dendritic contacts between SACs and DSGCs. Furthermore, examination of the inhibitory input pattern on the dendrites of DSGCs using antibodies against GABAA receptors also suggested an isotropic arrangement with the overlapping SACs in both the preferred and the null directions. Therefore, the presynaptic mechanism of direction selectivity upon DSGCs may not result from a simple asymmetric arrangement with overlapping SACs. Multiple layer interactions and sophisticated synaptic connections between SACs and DSGCs are necessary. J. Comp. Neurol. 508:175,183, 2008. © 2008 Wiley-Liss, Inc. [source] Synaptic connections of cholinergic antennal lobe relay neurons innervating the lateral horn neuropile in the brain of Drosophila melanogasterTHE JOURNAL OF COMPARATIVE NEUROLOGY, Issue 3 2003Kouji Yasuyama Abstract Presumed cholinergic projection neurons (PNs) in the brain of the fruit fly Drosophila melanogaster, immunoreactive to choline acetyltransferase (ChAT), convey olfactory information between the primary sensory antennal lobe neuropile and the mushroom body calyces, and finally terminate in the lateral horn (LH) neuropile. The texture and synaptic connections of ChAT PNs in the LH and, comparatively, in the smaller mushroom body calyces were investigated by immuno light and electron microscopy. The ChAT PN fibers of the massive inner antennocerebral tract (iACT) extend into all portions of the LH, distributing in a nonrandom fashion. Immunoreactive boutons accumulate in the lateral margins of the LH, whereas the more proximal LH exhibits less intense immunolabeling. Boutons with divergent presynaptic sites, unlabeled as well as ChAT-immunoreactive, appear to be the preponderant mode of synaptic input throughout the LH. Synapses of ChAT-labeled fibers appear predominantly as divergent synaptic boutons (diameters 1,3 ,m), connected to unlabeled postsynaptic profiles, or alternatively as a minority of tiny postsynaptic spines (diameters 0.05,0.5 ,m) among unlabeled profiles. Together these spines encircle unidentified presynaptic boutons of interneurons which occupy large areas of the LH. Thus, synaptic circuits in the LH differ profoundly from those of the PNs in the mushroom body calyx, where ChAT spines have not been encountered. Synaptic contacts between LH ChAT elements were not observed. The synaptic LH neuropile may serve as an output area for terminals of the ChAT PNs, their presynaptic boutons providing input to noncholinergic relay neurons. The significance of the postsynaptic neurites of the ChAT PNs is discussed; either local or other interneurons might connect the ChAT PNs within the LH, or PNs might receive inputs arising from outside the LH. J. Comp. Neurol. 466:299,315, 2003. © 2003 Wiley-Liss, Inc. [source] Developmental alterations in the functional properties of excitatory neocortical synapsesTHE JOURNAL OF PHYSIOLOGY, Issue 9 2009Dirk Feldmeyer In the neocortex, most excitatory, glutamatergic synapses are established during the first 4,5 weeks after birth. During this period profound changes in the properties of synaptic transmission occur. Excitatory postsynaptic potentials (EPSPs) at immature synaptic connections are profoundly and progressively reduced in response to moderate to high frequency (5,100 Hz) stimulation. With maturation, this frequency-dependent depression becomes progressively weaker and may eventually transform into a weak to moderate EPSP facilitation. In parallel to changes in the short-term plasticity, a reduction in the synaptic reliability occurs at most glutamatergic neocortical synapses: immature synapses show a high probability of neurotransmitter release as indicated by their low failure rate and small EPSP amplitude variation. This high reliability is reduced in mature synapses, which show considerably higher failure rates and more variable EPSP amplitudes. During early neocortical development synaptic vesicle pools are not yet fully differentiated and their replenishment may be slow, thus resulting in EPSP amplitude depression. The decrease in the probability of neurotransmitter release may be the result of an altered Ca2+ control in the presynaptic terminal with a reduced Ca2+ influx and/or a higher Ca2+ buffering capacity. This may lead to a lower synaptic reliability and a weaker short-term synaptic depression with maturation. [source] Synaptic heterogeneity between mouse paracapsular intercalated neurons of the amygdalaTHE JOURNAL OF PHYSIOLOGY, Issue 1 2007Raffaella Geracitano GABAergic medial paracapsular intercalated (Imp) neurons of amygdala are thought of as playing a central role in fear learning and extinction. We report here that the synaptic network formed by these neurons exhibits distinct short-term plastic synaptic responses. The success rate of synaptic events evoked at a frequency range of 0.1,10 Hz varied dramatically between different connected cell pairs. Upon enhancing the frequency of stimulation, the success rate increased, decreased or remained constant, in a similar number of cell pairs. Such synaptic heterogeneity resulted in inhibition of the firing of the postsynaptic neurons with different efficacies. Moreover, we found that the different synaptic weights were mainly determined by diversity in presynaptic release probabilities rather than postsynaptic changes. Sequential paired recording experiments demonstrated that the same presynaptic neuron established the same type of synaptic connections with different postsynaptic neurons, suggesting the absence of target-cell specificity. Conversely, the same postsynaptic neuron was contacted by different types of synaptic connections formed by different presynaptic neurons. A detailed anatomical analysis of the recorded neurons revealed discrete and unexpected peculiarities in the dendritic and axonal patterns of different cell pairs. In contrast, several intrinsic electrophysiological responses were homogeneous among neurons, and synaptic failure counts were not affected by presynaptic cannabinoid 1 or GABAB receptors. We propose that the heterogeneous functional connectivity of Imp neurons, demonstrated by this study, is required to maintain the stability of firing patterns which is critical for the computational role of the amygdala in fear learning and extinction. [source] Immunocytochemical Detection of Synaptophysin in Enteric Neurones during Prenatal Development in the Rat StomachANATOMIA, HISTOLOGIA, EMBRYOLOGIA, Issue 3 2004M. Asar Summary In this study, the localization and appearance of synaptophysin-immunoreactive (IR) nerve cells and their relationships with the developing gastric layers were studied by immunocytochemistry and light microscopy in the embryonic rat stomach. The stomachs of Wistar rat embryos aged 13,21 days were used. The first neuronal bodies and their processes containing synaptophysin-immunoreactivity were observed on embryonic day 13. In contrast, synaptophysin-IR nerve terminals were first observed between mesenchymal cells on embryonic day 14. These results indicate that synaptophysin is expressed in growing neurits and neuronal cell bodies before these neurones have established synaptic connections. The occurrences of mesenchymal cell condensation near synaptophysin-IR neuroblasts on embryonic day 15 reflect an active nerve element-specific mesenchymal cell induction resulting in the morphogenesis of muscle cells. Similarly, the appearance of glandular structures after synaptophysin-IR neuroblasts, on embryonic day 18, suggests that the epithelial differentiation may be closely related to the neuronal maturation as well as other factors. Finally, synaptophysin is functionally important in neuronal development and maturation, together with the establishment of neuroneuronal and neuromuscular contacts and in epithelial differentiation. [source] | ||||||||||||||||||||||||||||