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Results for “Neuronal Plasticity”

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PubMed2003

Plasticity of the nigropallidal pathway in Parkinson's disease.

The degeneration of nigrostriatal dopamine neurons in early Parkinson's disease (PD) is compensated in part by increased transmitter turnover in surviving neurons of the pathway. In this (18)F-dopa positron emission tomography study, we demonstrate compensatory changes in PD in another midbrain dopamine projection to the basal ganglia, the nigropallidal projection to the internal segment of the globus pallidus (GPi). Increased (18)F-dopa uptake in the GPi is seen in early PD which then is lost in advanced PD. Our early PD cases show an absence of significant clinical progression in the face of a continuing loss of nigrostriatal projections. This indicates a compensatory neuronal plasticity that we now show to involve the nigropallidal dopamine pathway to the GPi but not to the external segment of the globus pallidus (GPe). Enhanced function of the dopamine projection to the GPi serves, we propose, to maintain a more normal pattern of pallidal output to ventral thalamus and motor cortex in early PD, whereas loss of this adaptive pathway in advanced disease may be a pivotal step in the progression of the disease.

Adult↗

PubMed2002

A brain adaptation view of plasticity: is synaptic plasticity an overly limited concept?

A view that is emerging is that the brain has multiple forms of plasticity that must be governed, at least in part, by independent mechanisms. This view is illustrated by: (1) the apparent separate governance of some non-neural changes by activity, in contrast to synaptic changes driven by learning; (2) the apparent independence of different kinds of synaptic changes that occur in response to the learning aspects of training; (3) the occurrence of separate patterns of synaptic plasticity in the same system in response to different task demands; and (4) apparent dissociations between behaviorally induced synaptogenesis and LTP. The historical focus of research and theory in areas ranging from learning and memory to experiential modulation of brain development has been heavily upon synaptic plasticity since shortly after the discovery of the synapse. Based upon available data, it could be argued that: (1) synaptic, and even neuronal, plasticity is but a small fraction of the range of changes that occur in response to experience; and (2) we are just beginning to understand the importance of these other forms of brain plasticity. Appreciation of this aspect of the brain's adaptive process may allow us to better understand the capacity of the brain to tailor a particular set of changes to the demands of the specific experiences that generated them.

Adaptation, Physiological↗

PubMed2006

Density and morphology of dendritic spines in mouse neocortex.

Dendritic spines of pyramidal cells are the main postsynaptic targets of cortical excitatory synapses and as such, they are fundamental both in neuronal plasticity and for the integration of excitatory inputs to pyramidal neurons. There is significant variation in the number and density of dendritic spines among pyramidal cells located in different cortical areas and species, especially in primates. This variation is believed to contribute to functional differences reported among cortical areas. In this study, we analyzed the density of dendritic spines in the motor, somatosensory and visuo-temporal regions of the mouse cerebral cortex. Over 17,000 individual spines on the basal dendrites of layer III pyramidal neurons were drawn and their morphologies compared among these cortical regions. In contrast to previous observations in primates, there was no significant difference in the density of spines along the dendrites of neurons in the mouse. However, systematic differences in spine dimensions (spine head size and spine neck length) were detected, whereby the largest spines were found in the motor region, followed by those in the somatosensory region and those in visuo-temporal region.

Animals↗

PubMed2001

Localization of low affinity nerve growth factor receptor in the rat inferior olivary complex during development and plasticity of climbing fibres.

The rat olivocerebellar pathway has a precise topography from an inferior olive (IOC) to Purkinje cells in the contralateral hemicerebellum. While its development and plasticity have been documented, the molecular mechanisms underlying these events are not fully elucidated. Neurotrophins are a family of growth factors with diverse roles in development and neuronal plasticity, acting through a two-receptor system, including a low affinity receptor (LNGFR) which binds all neurotrophins with similar affinity. Since neurotrophins are present in the cerebellum during early postnatal development when LNGFR is synthesized in the IOC, they may act as target-derived trophic agents for climbing fibres during development and plasticity. To assess this, standard immunohistochemistry was used to document the distribution of LNGFR in the rat IOC during climbing fibre development and until cerebellar development was complete at postnatal day 28 (P28). LNGFR immunoreactivity (LNGFR-IR) was detected in the IOC from P0 until P15, however after P7 it diminished in intensity and distribution, a change which indicates a relationship between cerebellar neurotrophins and climbing fibre development. After denervation of the left hemicerebellum, there was an apparent increase in inferior olivary LNGFR-IR that was concurrent with climbing fibre re-innervation. Thus the results of this study support the hypothesis that neurotrophins are involved in climbing fibre development and suggest a possible contribution to the plasticity of the olivocerebellar pathway.

Animals↗

PubMed1997

Plasticity of synaptic connections in sensory-motor pathways of the adult locust flight system.

We investigated possible roles of retrograde signals and competitive interactions in the lesion-induced reorganization of synaptic contacts in the locust CNS. Neuronal plasticity is elicited in the adult flight system by removal of afferents from the tegula, a mechanoreceptor organ at the base of the wing. We severed one hindwing organ and studied the resulting rearrangement of synaptic contacts between flight interneurons and afferent neurons from the remaining three tegulae (2 forewing, 1 hindwing). This was done by electric stimulation of afferents and intracellular recording from interneurons (and occasionally motoneurons). Two to three weeks after unilateral tegula lesion, connections between tegula afferents and flight interneurons were altered in the following way. 1) Axons from the forewing tegula on the operated side had established new synaptic contacts with metathoracic elevator interneurons. In addition, the amplitude of compound excitatory postsynaptic potentials elicited by electric stimulation was increased, indicating that a larger number of afferents connected to any given interneuron. 2) On the side contralateral to the lesion, connectivity between axons from the forewing tegula and elevator interneurons was decreased. 3) The efficacy of the (remaining) hindwing afferents appeared to be increased with regard to both synaptic transmission to interneurons and impact on flight motor pattern. 4) Flight motoneurons, which are normally restricted to the ipsilateral hemiganglion, sprouted across the ganglion midline after unilateral tegula removal and apparently established new synaptic contacts with tegula afferents on that side. The changes on the operated side are interpreted as occupation of synaptic space vacated on the interneurons by the severed hindwing afferents. On the contralateral side, the changes in synaptic contact must be elicited by retrograde signals from bilaterally arborizing flight interneurons, because tegula projections remain strictly ipsilateral. The pattern of changes suggests competitive interactions between forewing and hindwing afferents. The present investigation thus presents evidence that the CNS of the mature locust is capable of extensive synaptic rearrangement in response to injury and indicates for the first time the action of retrograde signals from interneurons.

Animals↗

PubMed1996

Calcium and Free Radicals: Mediators of neurotrophic factor and excitatory transmitter-regulated developmental plasticity and cell death.

An intricate interplay between neurotrophic factor and excitatory transmitter signaling systems exists in both the developing and adult brain. Interactions between these signaling systems appears to be a fundamental mechanism regulating adaptive neuritic pruning and cell death. Accordingly, genetically and environmentally induced imbalances in this regulatory system are implicated in the pathogenesis of a variety of acute (such as stroke and traumatic brain injury) and chronic (such as Alzheimer's and Parkinson's diseases) neurodegenerative disorders. Neurons exhibit both acute and delayed responses to neurotrophic factors and excitatory transmitters; acute responses include rapid structural remodeling of growth cones and synaptic contacts, and delayed responses include induction or suppression of the expression of gene products involved in neuroprotection. Intracellular free Ca2+ and free radicals appear to play key roles as mediators of both acute and delayed responses of neurons to excitatory transmitters and neurotrophic factors. For example, the delayed response to bFGF includes stabilization of Ca2+ homeostasis and induction of antioxidant enzymes; both of these actions of bFGF antagonize the dendrite outgrowth-stabilizing and excitotoxic actions of glutamate. Intricate regulatory interactions exist between glutamate and neurotrophic factor signaling systems so that glutamate can induce the expression of neurotrophic factors and their receptors, and neurotrophic factors modulate the expression of exitatory transmitter receptors. A novel signaling system that can interact with both glutamate and neurotrophic factor systems is that of the beta-amyloid precursor protein, which appears to play important roles in neuronal plasticity and survival. A working model for the regulation of neuronal survival and connectivity is presented, which considers spatial and temporal constraints on release of, and receptors for, neurotrophic factors and excitatory transmitters.

Animals↗

PubMed2001

Polysialylated neural cell adhesion molecule is involved in the neuroplasticity induced by axonal injury in the avian ciliary ganglion.

We demonstrated previously in the quail ciliary ganglion, that the immunoreactivity for the neural cell adhesion molecule labeling the postsynaptic specializations of intraganglionic synapses decreases when synaptic remodeling is induced by crushing the postganglionic ciliary nerves. Here we show, in the same experimental conditions, that the immunolabeling for its polysialylated non-stabilizing isoform, which promotes cell plasticity, increases at these subcellular compartments. In control ganglia, poor immunolabeling for the polysialylated neural cell adhesion molecule was occasionally observed surrounding the soma of the ciliary neurons, in correspondence with the calyciform presynaptic ending and the perineuronal satellite cells sheath. At the electron microscope, several neuronal compartments, including some postsynaptic specializations, somatic spines and multivesicular bodies, were immunopositive. Three to six days after ciliary nerve crush, both the number of ciliary neurons labeled for the polysialylated neural cell adhesion molecule and the intensity of their immunolabeling increased markedly. Electron microscopy revealed that, in parallel to the injury-induced detachment of the preganglionic boutons, numerous postsynaptic specializations were found to be immunopositive. Twenty days later, when intraganglionic connections were re-established, polysialylated neural cell adhesion molecule immunoreactivity was comparable to that observed in control ganglia. The increase in immunolabeling also involved the other neuronal compartments mentioned above, the perineuronal satellite cells and the intercellular space between these and the ciliary neurons. From these results we suggest that the switch, at the postsynaptic specializations, between the neural cell adhesion molecule and its polysialylated form may be among the molecular changes occurring in axotomized neurons leading to injury-induced synaptic remodeling. Moreover, from the increase in polysialylated neural cell adhesion molecule immunolabeling, observed at the somatic spines and at the interface between neurons and perineuronal satellite cells, we suggest that this molecule may be involved not only in synaptic remodeling, but also in other more general aspects of injury-induced neuronal plasticity.

Animals↗

PubMed1994

Molecular consequences of diffusible signaling: locally distributed synaptic enhancement in hippocampal neurons.

The long-lasting increase in synaptic strength known as long-term potentiation is regarded as a potential physiological mechanism for many forms of both developmental and adult neuronal plasticity. In many models of plasticity, intercellular communication has been proposed to account for observations in which simultaneously active neurons are strengthened together. Recent studies indicate that long-term potentiation can be communicated between synapses on neighboring neurons, perhaps via a diffusible messenger. This distributed potentiation provides a potential mechanism for the cooperative strengthening of proximal synapses that underlie common neuronal functions and contribute to a variety of plastic processes in the nervous system.

Animals↗

PubMed2004

Inhibition of phosphodiesterase 2 increases neuronal cGMP, synaptic plasticity and memory performance.

An essential element of the signalling cascade leading to synaptic plasticity is the intracellular second messenger molecule guanosine 3',5'-cyclic monophosphate (cGMP). Using the novel, potent, and selective inhibitor Bay 60-7550, we show that the enzyme 3',5'-cyclic nucleotide phosphodiesterase type 2 (PDE2) is responsible for the degradation of newly synthesized cGMP in cultured neurons and hippocampal slices. Inhibition of PDE2 enhanced long-term potentiation of synaptic transmission without altering basal synaptic transmission. Inhibition of PDE2 also improved the performance of rats in social and object recognition memory tasks, and reversed MK801-induced deficits in spontaneous alternation in mice in a T-maze. Our data provide strong evidence that inhibition of PDE2 can improve memory functions by enhancing neuronal plasticity.

Animals↗

PubMed1998

Stress, glucocorticoids and structural plasticity of the hippocampus.

Sustained stress can have numerous pathophysiological effects. Adrenal glucocorticoid hormones are principal effectors in the stress response. They have profound effects on mood and behavior and affect neurochemical transmission and neuroendocrine control. We have used the experimental paradigm of chronic psychosocial stress in tree shrews to investigate the impact of aversive social encounters on brain structures. Chronic stress in male tree shrews which is accompanied by constantly elevated levels of glucocorticoids leads to structural changes in hippocampal neurons. Whereas dendritic atrophy of hippocampal pyramidal neurons and impairment of neurogenesis in the dentate gyrus could be demonstrated in chronically stressed tree shrews, a loss of hippocampal neurons was not observed in this animal model. The present review summarizes recent results on the question which structural changes occur during chronic stress in neurons of the brain and whether glucocorticoids might be responsible for such stress effects. The role of transmitter systems in stress-related neuronal plasticity is also discussed.

Animals↗

PubMed2005

What can a neuron learn with spike-timing-dependent plasticity?

Spiking neurons are very flexible computational modules, which can implement with different values of their adjustable synaptic parameters an enormous variety of different transformations F from input spike trains to output spike trains. We examine in this letter the question to what extent a spiking neuron with biologically realistic models for dynamic synapses can be taught via spike-timing-dependent plasticity (STDP) to implement a given transformation F. We consider a supervised learning paradigm where during training, the output of the neuron is clamped to the target signal (teacher forcing). The well-known perceptron convergence theorem asserts the convergence of a simple supervised learning algorithm for drastically simplified neuron models (McCulloch-Pitts neurons). We show that in contrast to the perceptron convergence theorem, no theoretical guarantee can be given for the convergence of STDP with teacher forcing that holds for arbitrary input spike patterns. On the other hand, we prove that average case versions of the perceptron convergence theorem hold for STDP in the case of uncorrelated and correlated Poisson input spike trains and simple models for spiking neurons. For a wide class of cross-correlation functions of the input spike trains, the resulting necessary and sufficient condition can be formulated in terms of linear separability, analogously as the well-known condition of learnability by perceptrons. However, the linear separability criterion has to be applied here to the columns of the correlation matrix of the Poisson input. We demonstrate through extensive computer simulations that the theoretically predicted convergence of STDP with teacher forcing also holds for more realistic models for neurons, dynamic synapses, and more general input distributions. In addition, we show through computer simulations that these positive learning results hold not only for the common interpretation of STDP, where STDP changes the weights of synapses, but also for a more realistic interpretation suggested by experimental data where STDP modulates the initial release probability of dynamic synapses.

Action Potentials↗

PubMed2004

Independent regulation of synaptic size and activity by the anaphase-promoting complex.

Neuronal plasticity relies on tightly regulated control of protein levels at synapses. One mechanism to control protein abundance is the ubiquitin-proteasome degradation system. Recent studies have implicated ubiquitin-mediated protein degradation in synaptic development, function, and plasticity, but little is known about the regulatory mechanisms controlling ubiquitylation in neurons. In contrast, ubiquitylation has long been studied as a central regulator of the eukaryotic cell cycle. A critical mediator of cell-cycle transitions, the anaphase-promoting complex/cyclosome (APC/C), is an E3 ubiquitin ligase. Although the APC/C has been detected in several differentiated cell types, a functional role for the complex in postmitotic cells has been elusive. We describe a novel postmitotic role for the APC/C at Drosophila neuromuscular synapses: independent regulation of synaptic growth and synaptic transmission. In neurons, the APC/C controls synaptic size via a downstream effector Liprin-alpha; in muscles, the APC/C regulates synaptic transmission, controlling the concentration of a postsynaptic glutamate receptor.

Anaphase-Promoting Complex-Cyclosome↗

PubMedDate not supplied

Insulin-like growth factors as mediators of functional plasticity in the adult brain.

Insulin-like growth factors (IGFs) are present in the brain throughout life. While their role as modulators of brain growth and differentiation during development is becoming apparent, their possible involvement in adult brain function is less known. Nevertheless, accumulating evidence indicates a role for IGFs in brain plasticity processes. Specifically, IGFs modulate synaptic efficacy by regulating synapse formation, neurotransmitter release and neuronal excitability. IGFs also provide constant trophic support to target cells in the brain and in this way maintain appropriate neuronal function. Pathological dearrangement of this trophic input may lead to brain disease. Molecular targets of the IGFs in the adult brain may include pre- and post-synaptic proteins involved in synaptic contacts, membrane channels, neurite-guiding molecules, extracellular matrix components and glial-derived intercellular messengers. Future studies on the role of IGFs in the adult brain may help unravel the relationship between neuronal plasticity and brain disease.

Adult↗

PubMed1991

A requirement for the intercellular messenger nitric oxide in long-term potentiation.

Long-term potentiation (LTP) of synaptic transmission is a widely studied model of neuronal plasticity. The induction of LTP is known to require processes in the postsynaptic neuron, while experimental evidence suggests that the expression of LTP may occur in the presynaptic terminal. This has led to speculation that a retrograde messenger travels from the post- to the presynaptic cell during induction of LTP. Extracellular application or postsynaptic injection of two inhibitors of nitric oxide synthase, N-nitro-L-arginine or NG-methyl-L-arginine, blocks LTP. Extracellular application of hemoglobin, which binds nitric oxide, also attenuates LTP. These findings suggest that nitric oxide liberated from postsynaptic neurons may travel back to presynaptic terminals to cause LTP expression.

Amino Acid Oxidoreductases↗

PubMed1990

Visualizing unstained neurons in living brain slices by infrared DIC-videomicroscopy.

With a combination of infrared illumination, differential interference contrast (DIC) and image intensification by video, unstained living neurons have been visualized up to a depth of 50-100 microns in 300-microns thick brain slices. Recording and application pipettes could be placed under visual guidance. When applied to slices from rat neocortex and hippocampus, pyramidal and non-pyramidal neurons could be differentiated with medium magnification (20x-40x objective). Local neuronal clusters and bundling of apical dendrites of pyramidal cells were visible. The use of an objective with high numerical aperture (63x, N.A. 1.4) allowed the visualization of structures in the submicron range in neocortex and hippocampus. In combination with electrophysiological recordings, infrared DIC-videomicroscopy should facilitate the search for morphological changes underlying neuronal plasticity and the characterization of neuronal networks.

Animals↗

PubMed2005

Spinal-supraspinal serotonergic circuits regulating neuropathic pain and its treatment with gabapentin.

Not all neuropathic pain patients gain relief from current therapies that include the anticonvulsant, gabapentin, thought to modulate calcium channel function. We report a neural circuit that is permissive for the effectiveness of gabapentin. Substance P-saporin (SP-SAP) was used to selectively ablate superficial dorsal horn neurons expressing the neurokinin-1 receptor for substance P. These neurons project to the brain as shown by retrograde labelling and engage descending brainstem serotonergic influences that enhance spinal excitability via a facilitatory action on 5HT(3) receptors. We show the integrity of this pathway following nerve injury contributes to the behavioural allodynia, neuronal plasticity of deep dorsal horn neurons and the injury-specific actions of gabapentin. Thus SP-SAP attenuated the tactile and cold hypersensitivity and abnormal neuronal coding (including spontaneous activity, expansion of receptive field size) seen after spinal nerve ligation. Furthermore the powerful actions of gabapentin after neuropathy were blocked by either ablation of NK-1 expressing neurones or 5HT(3) receptor antagonism using ondansetron. Remarkably, 5HT(3) receptor activation provided a state-dependency (independent of that produced by neuropathy) allowing GBP to powerfully inhibit in normal uninjured animals. This circuit is therefore a crucial determinant of the abnormal neuronal and behavioural manifestations of neuropathy and importantly, the efficacy of gabapentin. As this spino-bulbo-spinal circuit contacts areas of the brain implicated in the affective components of pain, this loop may represent a route by which emotions can influence the degree of pain in a patient, as well as the effectiveness of the drug treatment. These hypotheses are testable in patients.

Action Potentials↗

PubMed2002

Rehabilitation and outcome following pediatric traumatic brain injury.

The long-term outcome for a child who has sustained a traumatic brain injury must be viewed in the context of ongoing development and maturation. Although neuronal plasticity provides the potential for neuronal reorganization in a child's brain, it is the behavioral demands of the environment that allow the child to take advantage of this potential and to maximize recovery. Pediatric rehabilitation is the setting that provides the necessary experiences for stimulating neuronal reorganization following TBI. However, neuronal reorganization has a cost to long-term development. The ultimate long-term impact of a TBI sustained in childhood depends on the child's ability to achieve developmental milestones following injury. Although injury-related and treatment-related factors are critical during the early stages of recovery, patient-related factors such as age-at-injury, developmental achievement at time of injury, maturation, and family involvement and resources impact the later stages of recovery. The process of pediatric rehabilitation following TBI is to provide an enriched, stimulating environment tailored to the needs of the child and based on real-word experiences. Early in the recovery process, pediatric rehabilitation is the setting that maximizes the potential for neuronal reorganization. Early rehabilitation also prepares the family for the child's long-term recovery and developmental needs. Involvement and training of family members early in the recovery process is critical for successful long-term outcome. Family members are the individuals best equipped to ensure treatment compliance and follow through with treatment recommendations, in maintaining treatment gains, and in generalizing treatment effects beyond the medical settings. Despite the life-long ramifications of childhood TBI, pediatric rehabilitation is the necessary step in promoting recovery and successful long-term outcome.

Brain Damage, Chronic↗

PubMed1998

CaMKIIbeta functions as an F-actin targeting module that localizes CaMKIIalpha/beta heterooligomers to dendritic spines.

Ca2+/calmodulin-dependent protein kinase II (CaMKII) is a serine/threonine protein kinase that regulates long-term potentiation and other forms of neuronal plasticity. Functional differences between the neuronal CaMKIIalpha and CaMKIIbeta isoforms are not yet known. Here, we use green fluorescent protein-tagged (GFP-tagged) CaMKII isoforms and show that CaMKIIbeta is bound to F-actin in dendritic spines and cell cortex while CaMKIIalpha is largely a cytosolic enzyme. When expressed together, the two isoforms form large heterooligomers, and a small fraction of CaMKIIbeta is sufficient to dock the predominant CaMKIIalpha to the actin cytoskeleton. Thus, CaMKIIbeta functions as a targeting module that localizes a much larger number of CaMKIIalpha isozymes to synaptic and cytoskeletal sites of action.

3T3 Cells↗