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    Developmental modulation of synaptic transmission by acetylcholine in the primary visual cortex

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    Despite the evidence that cortical synaptic organization and cognitive functions are influenced by the activity of the cholinergic system during postnatal development, so far no information is available on the effects produced by acetylcholine (ACh) on synaptic transmission. In the present article, we show that the ability of visual cortex slices to respond to ACh depends on postnatal age. In adulthood, ACh exerts mainly a facilitatory action on synaptic transmission, depressing field potential (FP) amplitude only if applied at high concentrations (millimolar range). During early postnatal development, at postnatal day 13 (P13), facilitation by ACh was lacking, with depression of FP observed with concentration of ACh in the micromolar range. The magnitude of ACh facilitatory effects increases with age. The time course of ACh-dependent facilitation overlaps the developmental maturation of acetylcholinesterase (AChE), suggesting a close relationship between ACh action and AChE activity. Thus, age-dependent modification of the cholinergic modulatory action may affect cortical maturation by regulating the magnitude of synaptic transmission. (c) 2006 Elsevier B.V. All rights reserved

    THE ROLE OF CHOLINERGIC SYSTEM IN NEURONAL PLASTICITY: FOCUS ON VISUAL CORTEX AND MUSCARINIC RECEPTORS

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    This review is focused on the basal forebrain (BFB) cholinergic system, cholinergic receptors and cholinoceptive target areas such as the neocortex, all of which are intimately involved in high cognitive functions and synaptic plasticity. The neurons of the BFB synthesize acetylcholine (ACh) whose action is mediated by two subclasses of receptors, namely nicotinic and muscarinic receptors. Using the visual system as a model, the aim here is to integrate and discuss the current knowledge on anatomy, ontogeny and function of the BFB cholinergic system. This signaling system represents the anatomo-functional basis of ACh action on neuronal network, neuronal plasticity and cognitive functions. Cholinergic system role on higher brain functions has received increasing attention since the first observation of A. Alzheimer (1907) reporting dramatic changes of the BFB cholinergic neuro-anatomy in one of the most devastating neUrodegenerative diseases of adult brain, i.e. Alzheirner's disease (AD). In addition to this observation, later work demonstrated its participation in deep re-arrangements of brain connectivity such as the regulation of neuronal plasticity during maturation of cortical sensory maps, in adult and aged brain

    Nerve growth factor favours long-term depression over long-term potentiation in layer II-III neurones of rat visual cortex

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    Nerve growth factor (NGF) has been shown to regulate plasticity in the visual cortex of monocularly deprived animals. However, to date, few attempts have been made to investigate the role of NGF in synaptic plasticity at the cellular level. In the study reported here we looked at the effects of exogenously applied NGF on synaptic plasticity of layer II-III regular spiking (RS) neurones in visual cortex of 16- to 18-day-old rats. We found that local application of NGF converted high frequency stimulation (HFS)-induced long-term potentiation (LTP) into long-term depression (LTD). We showed that this shift of synaptic plasticity was also obtained with bath application of NGF during HFS. Application of NGF subsequent to HFS left LTP unaffected, conferring temporal constraints on NGF efficacy. NGF effects on LTP were mediated by TrkA receptors. Indeed, blockade of TrkA by monoclonal antibody prevented NGF from inducing LTD following HFS. Low frequency stimulation (LFS) elicited LTD in RS cells. We found that NGF or blockade of NGF signalling by anti-TrkA antibody did not change the amplitude of the LTD induced by LFS. Thus, the NGF effect is selective for synaptic modifications induced by HFS in RS cells. The present results indicate that NGF may modulate the sign of long-term changes of synaptic efficacy in response to high frequency inputs

    Nerve growth factor favours long-term depression over long-term potentiation in layer II-III neurones of rat visual cortex

    No full text
    Nerve growth factor (NGF) has been shown to regulate plasticity in the visual cortex of monocularly deprived animals. However, to date, few attempts have been made to investigate the role of NGF in synaptic plasticity at the cellular level. In the study reported here we looked at the effects of exogenously applied NGF on synaptic plasticity of layer II-III regular spiking (RS) neurones in visual cortex of 16- to 18-day-old rats. We found that local application of NGF converted high frequency stimulation (HFS)-induced long-term potentiation (LTP) into long-term depression (LTD). We showed that this shift of synaptic plasticity was also obtained with bath application of NGF during HFS. Application of NGF subsequent to HFS left Up unaffected, conferring temporal constraints on NGF efficacy. NGF effects on UP were mediated by TrkA receptors. Indeed, blockade of TrkA by monoclonal antibody prevented NGF from inducing LTD following HFS. Low frequency stimulation (LFS) elicited LTD in RS cells. We found that NGF or blockade of NGF signalling by anti-TrkA antibody did not change the amplitude of the LTD induced by LFS. Thus, the NGF effect is selective for synaptic modifications induced by HFS in RS cells. The present results indicate that NGF may modulate the sign of long-term changes of synaptic efficacy in response to high frequency inputs

    Acetylcholine modulates cortical synaptic transmission via different muscarinic receptors, as studied with receptor knockout mice

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    The central cholinergic system plays a crucial role in synaptic plasticity and spatial attention; however, the roles of the individual cholinergic receptors involved in these activities are not well understood at present. In the present study, we show that acetylcholine (ACh) can facilitate or depress synaptic transmission in occipital slices of mouse visual cortex. The precise nature of the ACh effects depends on the ACh concentration, and is input specific, as shown by stimulating different synaptic pathways. Pharmacological blockade of muscarinic receptor (mAChR) subtypes and the Use of M-1-M-5 mAChR-deficient mice showed that specific mAChR subtypes, together with the activity of the cholinesterases (ChEs), mediate facilitation or depression of synaptic transmission. The present data suggest that local ACh, acting through mAChRs, regulates the cortical dynamics making cortical circuits respond to specific stimuli

    Selective cholinergic immunolesioning affects synaptic plasticity in developing visual cortex

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    Cholinergic neurotransmission is known to affect activity-dependent plasticity in various areas, including the visual cortex. However, relatively little is known about the exact role of subcortical cholinergic inputs in the regulation of plastic events in this region during early postnatal development. In the present study, synaptic transmission and plasticity in the developing visual cortex were studied following selective immunotoxic removal of the basal forebrain cholinergic afferents in 4-day-old rat pups. The lesion produced dramatic cholinergic neuronal and terminal fibre loss associated with decreased mRNA levels for the M-1 and M-2 muscarinic receptors, as well as clear-cut impairments of long-term potentiation (LTP) in visual cortex slices. Indeed, after theta burst stimulation of layer IV a long-term depression (LTD) instead of an LTP was induced in immunolesioned slices. This functional change appears to be due to the lack of cholinergic input as exogenous application of acetylcholine prevented the shift from LTP to LTD. In addition, lesioned rats showed an increased sensitivity to acetylcholine (ACh). While application of 20 mu m ACh produced a depression of the field potential in immunolesioned rat slices, in order to observe the same effect in control slices we had to increase ACh concentration to up to 200 mu m. Taken together, our results indicate that deprivation of cholinergic input affects synaptic transmission and plasticity in developing visual cortex, suggesting that the cholinergic system could play an active role in the refinement of the cortical circuitry during maturation

    Muscarinic acetylcholine receptor knockout mice show distinct synaptic plasticity impairments in the visual cortex

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    In the present report, we focused our attention on the role played by the muscarinic acetylcholine receptors(mAChRs)in different forms of long-term synaptic plasticity. Specifically, we investigated long-termpotentiation (LTP)and long-termdepression (LTD)expression elicited by theta-burst stimulation (TBS) and low-frequency stimulation (LFS), respectively, in visual cortical slices obtained from different mAChR knockout (KO) mice. A normal LTP was evoked in M1/M3 double KO mice, while LTP was impaired in the M2/M4 double KO animals. On the other hand, LFS induced LTD in M2/M4 double KO mice, but failed to do so inM1/M3 KO mice. Interestingly, LFS produced LTP instead of LTD in M1/M3 KO mice. Analysis of mAChR single KO mice revealed that LTP was affected only by the simultaneous absence of both M2 and M4 receptors. A LFS-dependent shift from LTDto LTP was also observed in slices fromM1 KOmice,while LTD was simply abolished in slices from M3 KO mice. Using pharmacological tools, we showed that LTP in control mice was blocked by pertussis toxin, an inhibitor of Gi/o proteins,but not by raising intracellular cAMP levels. In addition, the inhibition of phospholipase C by U73122 induced the same shift from LTD to LTP after LFS observed in M1 single KO and M1/M3 double KO mice. Our results indicate that different mAChR subtypes regulate different forms of long-term synaptic plasticity in the mouse visual cortex, activating specific G proteins and downstream intracellular mechanisms

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
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