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Results for “Neuronal Plasticity”

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At least 343 records · Page 19Linked to original sources
PubMed2002

Direct cleavage of AMPA receptor subunit GluR1 and suppression of AMPA currents by caspase-3: implications for synaptic plasticity and excitotoxic neuronal death.

Cysteine proteases of the caspase family play central roles in excecuting the cell death process in neurons during development of the nervous system and in neurodegenerative disorders. Recent findings suggest that caspases may also play roles in modulating neuronal plasticity in the absence of cell death. We previously reported that caspases can be activated in dendrites and synapses in response to activation of glutamate receptors. In the present study we demonstrate that the GluR1 subunit of the AMPA subtype of glutamate receptor is directly cleaved by caspase-3, and provide evidence that the cleavage of this subunit modulates neuronal excitability in ways that suggest important roles for caspases in regulating synaptic plasticity and cell survival. Whole-cell patch-clamp recordings in cultured rat hippocampal neurons showed that caspase activation in response to apoptotic stimuli selectively decreases AMPA channel activity without decreasing NMDA channel activity. Perfusion of neurons with recombinant caspase-3 resulted in a decreased AMPA current, demonstrating that caspase-3 activity is sufficient to suppress neuronal responses to glutamate. Exposure of radiolabeled GluR1 to recombinant caspase-3 resulted in cleavage of GluR1, demonstrating that this glutamate receptor protein is a direct substrate of this caspase. Our findings suggest roles for caspases in the modulation of neuronal excitability in physiological settings, and also identify a mechanism whereby caspases ensure that neurons die by apoptosis rather than excitotoxic necrosis in developmental and pathological settings.

Animals↗
PubMed1989

Neurotransmitter regulation of neuronal outgrowth, plasticity and survival.

Molecules used for communication in mature nervous systems also play important roles in development, maintenance and plasticity of individual neurons. This paper reviews the evidence that neurotransmitters, in addition to their mediation of trans-synaptic information coding, can induce a spectrum of effects on neuronal cytoarchitecture, ranging from neurite sprouting to dendritic pruning and even cell death. Such profound alterations may well constitute a part of the normal functioning and structuring of the nervous system as well as contribute to severe pathological processes.

Animals↗
PubMedDate not supplied

Role of Cdk5 in neuronal signaling, plasticity, and drug abuse.

Functional and structural neuronal plasticity are mediated by a complex network of biochemical signal transduction pathways that control the strength of specific synapses and the formation of new synapses de novo. The neuronal protein kinase Cdk5 has been implicated as being involved in numerous aspects of both functional and structural plasticity through its regulation of signal transduction pathways. In this review the findings of a number of studies are summarized that have advanced our understanding of how Cdk5 may be involved in these processes. We focus on the modulation of protein phosphatase activity in both the hippocampus and basal ganglia, and review findings that indicate Cdk5 is likely to regulate neuronal plasticity in these brain regions. Studies showing involvement of Cdk5 in reward and motor-based plasticity, which are thought to underlie drug abuse, are discussed.

Animals↗
PubMed2006

Plasticity within striatal direct pathway neurons after neonatal dopamine depletion is mediated through a novel functional coupling of serotonin 5-HT2 receptors to the ERK 1/2 map kinase pathway.

Dysfunction within the striatal direct and indirect projecting systems arises after 6-hydroxydopamine (6-OHDA)-induced dopamine depletion, highlighting the central regulatory function of dopamine in motor systems. However, the striatal 5-hydroxytryptamine (5-HT) innervation remains intact after 6-OHDA lesions, suggesting that the 5-HT system may contribute to the lesion-induced dysfunction, or alternatively, it may adapt and compensate for the dopamine deficit. Neonatal 6-OHDA lesions actually give rise to a 5-HT axonal hyperinnervation within the dorsal striatum, further reinforcing the idea that the 5-HT system plays a central role in striatal function after dopamine depletion. Here we show that neonatal but not adult 6-OHDA lesions result in a novel coupling of 5-HT2 receptors to the ERK1/2/MAP Kinase pathway, a signaling cascade known to regulate neuronal plasticity. Chloroamphetamine-induced 5-HT release or direct stimulation of striatal 5-HT2 receptors via the 5-HT2 agonist DOI, produced robust ERK1/2 phosphorylation throughout the dorsal striatum of neonatal lesioned animals, a response not observed within the intact striatum. Pretreatment with the select 5-HT2 receptor antagonist Ketanserin blocked DOI-induced ERK1/2 phosphorylation. This drug-induced ERK1/2 phosphorylation was subsequently shown to be restricted to direct pathway striatal neurons. Our data show that adaptation of direct pathway neurons after neonatal 6-OHDA lesions involves coupling of 5-HT2 receptors to the ERK1/2/MAP Kinase cascade, a pathway not typically active in these neurons. Because dopamine-mediated signaling is redundant after 6-OHDA lesions, 5-HT-mediated stimulation of the ERK1/2/MAP Kinase pathway may provide an alternative signaling route allowing the regulation of neuronal gene expression and neuronal plasticity in the absence of dopamine.

Animals↗
PubMedDate not supplied

[Neurotrophic factors and their role in the pathogenesis of affective disorders].

Neurotrophic factors are a group of proteins with a similar structure (The regulation of neuronal plasticity and neuron protection are some of their biological functions). The group of neurotrophic factors consists of: growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin 3 (NT-3) and neurotrophin 4/5 (NT-4/5). BDNF is the most important neurotrophin from the affective disorders point of view. Preclinical and clinical studies of altered BDNF expression during chronic stress and increased BDNF activity during antidepressant treatment, confirm the role of BDNF in the pathogenesis of depression. Studies on animal models point to the antidepressant effect of BDNF, similar to long-term antidepressant treatment. The intracellular mechanisms mediated by this neurotrophic factor are connected with signal transduction pathways in cells (mainly mitogen-activated protein kinase cascade and cyclic adenosine 3',5'-monophosphate cascade). The BDNF serum level studies suggest a correlation between the BDNF expression in the central nervous system and its serum levels, what could make BDNF levels specific markers of depression. The molecular genetic studies focus on associations between BDNF gene polymorphisms and bipolar disorder or cognitive functioning disturbances. The novel pathogenetic theories of depression based on neuronal plasticity (Duman et al.) and disturbances in neurogenesis (Kempermann and Kronenberg) can be a kind of recapitulation of research on the role of neurotrophins in depression. However many issues related to the role of neurotrophic factors in affective disorders are still unclear and determine areas of future scientific interests in this field.

Animals↗
PubMed2006

Cannabinoids Potentiate Emotional Learning Plasticity in Neurons of the Medial Prefrontal Cortex through Basolateral Amygdala Inputs.

Cannabinoids represent one of the most commonly used hallucinogenic drug classes. In addition, cannabis use is a primary risk factor for schizophrenia in susceptible individuals and can potently modulate the emotional salience of sensory stimuli. We report that systemic activation or blockade of cannabinoid CB1 receptors modulates emotional associative learning and memory formation in a subpopulation of neurons in the mammalian medial prefrontal cortex (mPFC) that receives functional input from the basolateral amygdala (BLA). Using in vivo single-unit recordings in rats, we found that a CB1 receptor agonist potentiated the response of medial prefrontal cortical neurons to olfactory cues paired previously with a footshock, whereas this associative responding was prevented by a CB1 receptor antagonist. In an olfactory fear-conditioning procedure, CB1 agonist microinfusions into the mPFC enabled behavioral responses to olfactory cues paired with normally subthreshold footshock, whereas the antagonist completely blocked emotional learning. These results are the first demonstration that cannabinoid signaling in the mPFC can modulate the magnitude of neuronal emotional learning plasticity and memory formation through functional inputs from the BLA.

Action Potentials↗
PubMed2004

Plasticity of neuronal responses induced by low concentrations of exogenous ligands affecting cellular calcium stores.

Modification of reactions caused by repeated influences (plasticity) is a fundamental property of cell. In this study, we have revealed effects of low concentrations of two exogenous modulators of cellular processes (caffeine and cyclosporin A) on neuronal plastic properties. The study was carried out on isolated neurons of Lymnaea stagnalis. It was found that low concentrations of caffeine or cyclosporin A did not cause any changes of the membrane potential (MP) of isolated neurons. However, pretreatment of neurons with low concentrations of caffeine or cyclosporin A reduced the amplitude of MP changes caused by the action of physiological concentrations of these ligands on the average by 30.8% and 29.1%, respectively. The findings permitted implying a significant role of low ligand concentrations in the formation of cell memory and neuronal plastic properties.

Animals↗
PubMed1995

Oestrogens and the structural and functional plasticity of neurons: implications for memory, ageing and neurodegenerative processes.

Oestrogens have numerous effects on the brain, beginning during gestation and continuing on into adulthood. Many of these actions involve areas of the brain that are not primarily involved in reproduction, such as the basal forebrain, hippocampus, caudate putamen, midbrain raphe and brainstem locus coeruleus. This paper describes three actions of oestrogens that are especially relevant to brain mechanisms involved in memory processes and their alterations during ageing and neurodegenerative diseases: (1) the regulation of cholinergic neurons by oestradiol in the rat basal forebrain, involving induction of choline acetyltransferase and acetylcholinesterase according to a sexually dimorphic pattern; (2) the regulation of synaptogenesis in the CA1 region of the hippocampus by oestrogens and progestins during the four- to five-day oestrus cycle of the female rat. Formation of new excitatory synapses is induced by oestradiol and involves N-methyl-D-aspartate receptors; removal of these synapses involves intracellular progestin receptors; (3) sex differences in hippocampal structure, which may help to explain differences in the strategies that male and female rats use to solve spatial navigation problems. During the period of development when testosterone is elevated in the male, aromatase and oestrogen receptors are also elevated, making it likely that this pathway is involved in the masculinization of hippocampal structure.

Aging↗
PubMed2006

A functional hypothesis for adult hippocampal neurogenesis: avoidance of catastrophic interference in the dentate gyrus.

The dentate gyrus is part of the hippocampal memory system and special in that it generates new neurons throughout life. Here we discuss the question of what the functional role of these new neurons might be. Our hypothesis is that they help the dentate gyrus to avoid the problem of catastrophic interference when adapting to new environments. We assume that old neurons are rather stable and preserve an optimal encoding learned for known environments while new neurons are plastic to adapt to those features that are qualitatively new in a new environment. A simple network simulation demonstrates that adding new plastic neurons is indeed a successful strategy for adaptation without catastrophic interference.

Adaptation, Physiological↗
PubMed2006

Plasticity of neurons and glia following neonatal hypoxic-ischemic brain injury in rats.

Periventricular white matter injury in premature infants is linked to chronic neurological dysfunction. Periventricular white matter injury is caused by many mechanisms including hypoxia-ischemia (HI). Animal models of HI in the neonatal rodent brain can replicate some important features of periventricular white matter injury. Most rodent studies have focused upon early cellular and tissue events following unilateral neonatal HI that is elicited by unilateral carotid artery ligation and followed by timed exposure to moderate hypoxia. Milder hypoxic-ischemic insults elicit preferential white matter injury. Little information is available about long-term cellular effects of unilateral HI. One month after unilateral neonatal hypoxia ischemia, we show that all the components for structural reorganization of the brain are present in moderately injured rats. These components in the injured side include extensive influx of neurites, axonal and dendritic growth cones, abundant immature synapses, and myelination of many small axons. Surprisingly, this neural recovery is often found in and adjacent to cysts that have the ultrastructural features of bone extracellular matrix. In contrast, brains with severe hypoxia ischemia one month after injury still undergo massive neuronal degeneration. While massive destruction of neurons and glia are striking events shortly after brain HI, neural cells re-express their intrinsic properties and attempt an anatomical recovery long after injury.

Animals↗
PubMed2006

Cannabinoids, electrophysiology, and retrograde messengers: challenges for the next 5 years.

Most of the behavioral effects of cannabis and its active ingredients, the cannabinoids (delta9THC being the most abundant of these), appear to be mediated by cannabinoid receptors. Endogenous cannabinoids (endocannabinoids) are lipid mediators that activate these same cannabinoid receptors. Elegant work from several laboratories over the past 5 years has established that endocannabinoids, possibly acting as retrograde messengers, mediate several forms of neuronal plasticity. Endocannabinoid-mediated neuronal plasticity is common, apparently occurring at all neurons that express cannabinoid receptors. Thus, it is likely that delta9THC produces its effects by interacting with endocannabinoid-mediated neuronal plasticity, though whether it does so cooperatively or antagonistically remains an open question. In this review we will briefly discuss the work establishing endocannabinoids as mediators of neuronal plasticity and then present evidence that a major effect of delta9THC may be to antagonize the actions of endocannabinoids.

Animals↗
PubMedDate not supplied

CREB activation mediates plasticity in cultured hippocampal neurons.

Activation of cyclic AMP dependent kinase is believed to mediate slow onset, long-term potentiation (LTP) in central neurons. Cyclic-AMP activates a cascade of molecular events leading to phosphorylation of the nuclear cAMP responsive element binding protein (pCREB). Whereas a variety of stimuli lead to activation of CREB, the molecular processes downstream of CREB, which may be relevant to neuronal plasticity, are yet largely unknown. We have recently found that following exposure to estradiol, pCREB mediates the large increase in dendritic spine density in cultured rat hippocampal neurons. We now extend these observations to include other stimuli, such as bicuculline, that cause the formation of new dendritic spines. Such stimuli share with estradiol the same mechanism of action in that both require activity-dependent CREB phosphorylation. Our observations suggest that CREB phosphorylation is a necessary, but perhaps not sufficient, step in the process leading to the generation of new dendritic spines and perhaps to functional plasticity as well.

Animals↗