Changes In Properties Of Neurons Research Articles

Repeated applications of high potassium elicit long-term changes in a motor circuit from the crab, Cancer borealis

SummaryWe examined the effects of altered extracellular potassium concentration on the output of the well-studied pyloric circuit in the crab, Cancer borealis. Pyloric neurons initially become quiescent, then recover spiking and bursting activity in high potassium saline (2.5x[K+]). These changes in circuit robustness are maintained after the perturbation is removed; pyloric neurons are more robust to subsequent potassium perturbations even after several hours of wash in control saline. Despite this long-term “memory” of the stimulus history, we found no differences in neuronal activity in control saline. The circuit’s adaptation is erased by both low potassium saline (0.4x[K+]) and direct hyperpolarizing current. Initial sensitivity of PD neurons to high potassium saline also varies seasonally, indicating that changes in robustness may reflect natural changes in circuit states. Thus, perturbation, followed by recovery of normal activity, can hide cryptic changes in neuronal properties that are only revealed by subsequent challenges.

How Is Peripheral Injury Signaled to Satellite Glial Cells in Sensory Ganglia?

Injury or inflammation in the peripheral branches of neurons of sensory ganglia causes changes in neuronal properties, including excessive firing, which may underlie chronic pain. The main types of glial cell in these ganglia are satellite glial cells (SGCs), which completely surround neuronal somata. SGCs undergo activation following peripheral lesions, which can enhance neuronal firing. How neuronal injury induces SGC activation has been an open question. Moreover, the mechanisms by which the injury is signaled from the periphery to the ganglia are obscure and may include electrical conduction, axonal and humoral transport, and transmission at the spinal level. We found that peripheral inflammation induced SGC activation and that the messenger between injured neurons and SGCs was nitric oxide (NO), acting by elevating cyclic guanosine monophosphate (cGMP) in SGCs. These results, together with work from other laboratories, indicate that a plausible (but not exclusive) mechanism for neuron-SGCs interactions can be formulated as follows: Firing due to peripheral injury induces NO formation in neuronal somata, which diffuses to SGCs. This stimulates cGMP synthesis in SGCs, leading to their activation and to other changes, which contribute to neuronal hyperexcitability and pain. Other mediators such as proinflammatory cytokines probably also contribute to neuron-SGC communications.

On the Origin of Paroxysmal Depolarization Shifts: The Contribution of Cav1.x Channels as the Common Denominator of a Polymorphous Neuronal Discharge Pattern

Since their discovery in the 1960s, the term paroxysmal depolarization shift (PDS) has been applied to a wide variety of reinforced neuronal discharge patterns. Occurrence of PDS as cellular correlates of electrographic spikes during latent phases of insult-induced rodent epilepsy models and their resemblance to giant depolarizing potentials (GDPs) nourished the idea that PDS may be involved in epileptogenesis. Both GDPs and – in analogy – PDS may lead to progressive changes of neuronal properties by generation of pulsatile intracellular Ca2+ elevations. Herein, a key element is the gating of L-type voltage gated Ca2+ channels (LTCCs, Cav1.x family), which may convey Ca2+ signals to the nucleus. Accordingly, the present study investigates various insult-associated neuronal challenges for their propensities to trigger PDS in a LTCC-dependent manner. Our data demonstrate that diverse disturbances of neuronal function are variably suited to induce PDS-like events, and the contribution of LTCCs is essential to evoke PDS in rat hippocampal neurons that closely resemble GDPs. These PDS appear to be initiated in the dendritic sub-compartment. Their morphology critically depends on the position of recording electrodes and on their rate of occurrence. These results provide novel insight into induction mechanisms, origin, variability, and co-existence of PDS with other discharge patterns and thereby pave the way for future investigations regarding the role of PDS in epileptogenesis.

Motor Recovery: How Rehabilitation Techniques and Technologies Can Enhance Recovery and Neuroplasticity.

There are now a large number of technological and methodological approaches to the rehabilitation of motor function after stroke. It is important to employ these approaches in a manner that is tailored to specific patient impairments and desired functional outcomes, while avoiding the hype of overly broad or unsubstantiated claims for efficacy. Here we review the evidence for poststroke plasticity, including therapy-related plasticity and functional imaging data. Early demonstrations of remapping in somatomotor and somatosensory representations have been succeeded by findings of white matter plasticity and a focus on activity-dependent changes in neuronal properties and connections. The methods employed in neurorehabilitation have their roots in early understanding of neuronal circuitry and plasticity, and therapies involving large numbers of repetitions, such as robotic therapy and constraint-induced movement therapy (CIMT), change measurable nervous systems properties. Other methods that involve stimulation of brain and peripheral excitable structures have the potential to harness neuroplastic mechanisms, but remain experimental. Gaps in our understanding of the neural substrates targeted by neurorehabilitation technology and techniques remain, preventing their prescriptive application in individual patients as well as their general refinement. However, with ongoing research-facilitated in part by technologies that can capture quantitative information about motor performance-this gap is narrowing. These research approaches can improve efforts to attain the shared goal of better functional recovery after stroke.

Tetrode Recording in the Xenopus laevis Visual System Using Multichannel Glass Electrodes.

The Xenopus tadpole visual system shows an extraordinary extent of developmental and visual experience-dependent plasticity, establishing sophisticated neuronal response properties that guide essential survival behaviors. The external development and access to the developing visual circuit of Xenopus tadpoles make them an excellent experimental system in which to elucidate plastic changes in neuronal properties and their capacity to encode information about the visual scene. The temporal structure of neural activity encodes a significant amount of information, access to which requires recording methods with high temporal resolution. Conversely, elucidating changes in the temporal structure of neural activity requires recording over extended periods. It is challenging to maintain patch-clamp recordings over extended periods and Ca2+ imaging has limited temporal resolution. Extracellular recordings have been used in other systems for extended recording; however, spike amplitudes in the developing Xenopus visual circuit are not large enough to be captured by distant electrodes. Here we describe a juxtacellular tetrode recording method for continuous long-term recordings from neurons in intact tadpoles, which can also be exposed to diverse visual stimulation protocols. Electrode position in the tectum is stabilized by the large contact area in the tissue. Contamination of the signal from neighboring neurons is minimized by the tight contact between the glass capillaries and the dense arrangement of neurons in the tectum. This recording method enables analysis of developmental and visual experience-dependent plastic changes in neuronal response properties at higher temporal resolution and over longer periods than current methods.

Нейрональные перестройки на супраспинальном уровне, способствующие кишечной гипералгезии при колите

Inflammatory bowel diseases (Crohn’s disease, ulcerative colitis) are characterized by chronic abdominal pain that persists even in the disease remission. The main cause of such pain is believed to be intestinal hyperalgesia, which develops as a result of the peripheral inflammation-induced impairments in the central, in particular, supraspinal mechanisms controlling visceral nociception. However, which brain structures and neuronal events are involved in the process remains unclear. Our study was aimed to determine the colitis-associated changes in neuronal properties of supraspinal structures, which can underlie development of intestinal hyperalgesia. The work was performed on urethane anesthetized male Wistar rats. Neuronal activity in various brain areas was assessed in healthy animals and rats with trinitrobenzenesulfonic acid-induced colitis by using the immunohistochemical method of determining c-fos protein expression and the microelectrode technique. Intestinal inflammation was accompanied by increased basal and nociceptive colorectal distension (CRD)-caused c-fos production in the caudal ventrolateral medulla (CVLM), nucleus tractus solitarius (NTS), parabrachial complex, and locus coeruleus. Under colitis, neuronal c-fos expression in the dorsal raphe nucleus was indifferent to CRD, whereas nociceptive c-fos activation in the midbrain central gray (MCG) was significantly reduced compared to that in norm. The microelectrode study in inflamed rats revealed an increase in the CRD-induced CVLM and NTS neuronal excitation and a decrease in the proportion of CRD-responsive MCG cells. The observed colitis-associated sensitization of the viscerosensory brainstem areas with a simultaneous decrease in excitability of the key structures belonging to the brain antinociceptive system can facilitate ascending visceral pain transmission, promoting intestinal hyperalgesia.

The mechanisms shaping CA2 pyramidal neuron action potential bursting induced by muscarinic acetylcholine receptor activation.

Recent studies have revealed that hippocampal area CA2 plays an important role in hippocampal network function. Disruption of this region has been implicated in neuropsychiatric disorders. It is well appreciated that cholinergic input to the hippocampus plays an important role in learning and memory. While the effect of elevated cholinergic tone has been well studied in areas CA1 and CA3, it remains unclear how changes in cholinergic tone impact synaptic transmission and the intrinsic properties of neurons in area CA2. In this study, we applied the cholinergic agonist carbachol and performed on-cell, whole-cell, and extracellular recordings in area CA2. We observed that under conditions of high cholinergic tone, CA2 pyramidal neurons depolarized and rhythmically fired bursts of action potentials. This depolarization depended on the activation of M1 and M3 cholinergic receptors. Furthermore, we examined how the intrinsic properties and action-potential firing were altered in CA2 pyramidal neurons treated with 10 µM carbachol. While this intrinsic burst firing persisted in the absence of synaptic transmission, bursts were shaped by synaptic inputs in the intact network. We found that both excitatory and inhibitory synaptic transmission were reduced upon carbachol treatment. Finally, we examined the contribution of different channels to the cholinergic-induced changes in neuronal properties. We found that a conductance from Kv7 channels partially contributed to carbachol-induced changes in resting membrane potential and membrane resistance. We also found that D-type potassium currents contributed to controlling several properties of the bursts, including firing rate and burst kinetics. Furthermore, we determined that T-type calcium channels and small conductance calcium-activated potassium channels play a role in regulating bursting activity.

The neuromorphological correlates of prolonged radiation exposure

Relevance.Liquidators of the consequences of radiation accidents have an increase in neuropsychiatric diseases. However, the structural and functional rearrangement of brain neurons under prolonged low radiation exposure remains virtually unexplored, which makes it difficult to assess the pathogenesis of these diseases.Intention.To study morphological correlates of prolonged low radiation effects on brain neurons in the model of radiobiological experiment.Method.270 white outbred male rats aged 4 months were exposed to radiation-quanta of 60Co in equal portions in total doses of 10; 20; 50 and 100 cGy with a dose rate of 0.5 Gy/h over 5 days. Age control consisted of animals exposed to false radiation. Animal studies complied with GLP standards. Brain fragments were taken after 1 day, 6, 12, 18 and 24 months after irradiation. After a standard histological treatment, changes in the tinctorial properties of neurons, their morphometric parameters, total protein and nucleic acids were evaluated.Results and their analysis. At the end of the observation period, the number of normochromic neurons decreased and the number of hyper and hypochromic cells increased, as well as their destructive forms. The neuro-cellular index decreased over time suggesting the death of some neurons, but without a statistically significant decrease in their number per area. In the post-irradiation period there were observed phase changes in the size of the cytoplasm, nucleus and nucleolus of neurons, as well as the content of protein and nucleic acids (RNA in the cytoplasm and nucleoli, DNA in the nuclei), more pronounced in irradiated animals and sometimes different from those observed in age control animals. As a result, a number of neuromorphological parameters in some periods of observation were not consistent with those in control animals, with a certain instability in the structural and functional organization of neurons.Conclusion.Prolonged low-dose ionizing radiation does not cause significant organic changes in the brain. However, increased radiation exposure or other concomitant adverse factors can be associated with further instability of the structural and functional organization of neurons and serve as a material substrate for a number of deviations in the central nervous system.

The Maintenance of Synaptic Homeostasis at the Drosophila Neuromuscular Junction Is Reversible and Sensitive to High Temperature.

Homeostasis is a vital mode of biological self-regulation. The hallmarks of homeostasis for any biological system are a baseline set point of physiological activity, detection of unacceptable deviations from the set point, and effective corrective measures to counteract deviations. Homeostatic synaptic plasticity (HSP) is a form of neuroplasticity in which neurons and circuits resist environmental perturbations and stabilize levels of activity. One assumption is that if a perturbation triggers homeostatic corrective changes in neuronal properties, those corrective measures should be reversed upon removal of the perturbation. We test the reversibility and limits of HSP at the well-studied Drosophila melanogaster neuromuscular junction (NMJ). At the Drosophila NMJ, impairment of glutamate receptors causes a decrease in quantal size, which is offset by a corrective, homeostatic increase in the number of vesicles released per evoked presynaptic stimulus, or quantal content. This process has been termed presynaptic homeostatic potentiation (PHP). Taking advantage of the GAL4/GAL80TS/UAS expression system, we triggered PHP by expressing a dominant-negative glutamate receptor subunit at the NMJ. We then reversed PHP by halting expression of the dominant-negative receptor. Our data show that PHP is fully reversible over a time course of 48–72 h after the dominant-negative glutamate receptor stops being genetically expressed. As an extension of these experiments, we find that when glutamate receptors are impaired, neither PHP nor NMJ growth is reliably sustained at high culturing temperatures (30–32°C). These data suggest that a limitation of homeostatic signaling at high temperatures could stem from the synapse facing a combination of challenges simultaneously.

Origins of Phantom Limb Pain.

Phantom limb pain (PLP) is a chronic neuropathic pain occurring in 45-85% of patients who undergo major amputations of the upper and lower extremities. Chronic pain is physically and mentally debilitating, affecting an individual's potential for self-care and the performance of daily living activities essential for personal and economic independence. In addition, chronic pain may lead to depression and feelings of hopelessness. A National Center for Biotechnology Information study found that in the USA alone, the annual cost of dealing with neuropathic pain is more than $600 billion, with an estimated 20 million people in the USA suffering this condition. PLP manifest predominantly during two time frames post-amputation: during days to a month and again at around 1year. In most patients, the frequency and intensity of the chronic neuropathic pain diminish over time, but severe pain persists in about 5-10% of patients. The development and maintenance of neuropathic pain is attributed to extremity amputations causing changes in peripheral axon properties and neuronal circuitry in both the peripheral and central nervous systems: peripheral axons, dorsal root ganglia, the spinal cord, and the cortex. However, it is not clear how the changes in neuronal properties in these different locations affect neuropathic pain. Is pain initiated by one set of post-amputation changes while the pain is maintained by another set of changes? If one set of amputation-induced changes, such as those of peripheral axons, are reverted to normal, is the chronic pain reduced or eliminated, while reversing another set of neuronal changes and neuronal circuits to normal do not reduce or eliminate the pain? Or, must all the amputation-induced changes be reverted to normal for pain to be eliminated? While this review examines the mechanisms underlying the induction or maintenance of PLP, it is beyond its scope to examine the mechanisms that may permanently reduce or eliminate neuropathic pain. This paper is the first of two reviews in this journal and deals with the causes of chronic PLP development and maintenance, while the second review examines potential mechanisms that may be responsible for promoting the capacity to coping with PLP by reducing or eliminating it.

Identification of postsynaptic phosphatidylinositol-4,5-bisphosphate (PIP2) roles for synaptic plasticity using chemically induced dimerization

Phosphatidylinositol-4,5-bisphosphate (PIP2), one of the key phospholipids, directly interacts with several membrane and cytosolic proteins at neuronal plasma membranes, leading to changes in neuronal properties including the feature and surface expression of ionotropic receptors. Although PIP2 is also concentrated at the dendritic spines, little is known about the direct physiological functions of PIP2 at postsynaptic as opposed to presynaptic sites. Most previous studies used genetic and pharmacological methods to modulate enzymes that alter PIP2 levels, making it difficult to delineate time- or region-specific roles of PIP2. We used chemically-induced dimerization to translocate inositol polyphosphate 5-phosphatase (Inp54p) to plasma membranes in the presence of rapamycin. Upon redistribution of Inp54p, long-term depression (LTD) induced by low-frequency stimulation was blocked in the mouse hippocampal CA3-CA1 pathway, but the catalytically-dead mutant did not affect LTD induction. Collectively, PIP2 is critically required for induction of LTD whereas translocation of Inp54p to plasma membranes has no effect on the intrinsic properties of the neurons, basal synaptic transmission, long-term potentiation or expression of LTD.

Glia as drivers of abnormal neuronal activity.

Reactive astrocytes have been proposed to become incompetent bystanders in epilepsy as a result of cellular changes rendering them unable to perform important housekeeping functions. Indeed, successful surgical treatment of mesiotemporal lobe epilepsy hinges on the removal of the glial scar. New research now extends the role of astrocytes, suggesting that they may drive the disease process by impairing the inhibitory action of neuronal GABA receptors. Here we discuss studies that include hyperexcitability resulting from impaired supply of astrocytic glutamine for neuronal GABA synthesis, and epilepsy resulting from genetically induced astrogliosis or malignant transformation, both of which render the inhibitory neurotransmitter GABA excitatory. In these examples, glial cells alter the expression or function of neuronal proteins involved in excitability. Although epilepsy has traditionally been thought of as a disease caused by changes in neuronal properties exclusively, these new findings challenge us to consider the contribution of glial cells as drivers of epileptogenesis in acquired epilepsies.

Changes in functional properties and 5-HT modulation above and below a spinal transection in lamprey.

In addition to the disruption of neural function below spinal cord injuries (SCI), there also can be changes in neuronal properties above and below the lesion site. The relevance of these changes is generally unclear, but they must be understood if we are to provide rational interventions. Pharmacological approaches to improving locomotor function have been studied extensively, but it is still unclear what constitutes an optimal approach. Here, we have used the lamprey to compare the modulatory effects of 5-HT and lesion-induced changes in cellular and synaptic properties in unlesioned and lesioned animals. While analyses typically focus on the sub-lesion spinal cord, we have also examined effects above the lesion to see if there are changes here that could potentially contribute to the functional recovery. Cellular and synaptic properties differed in unlesioned and lesioned spinal cords and above and below the lesion site. The cellular and synaptic modulatory effects of 5-HT also differed in lesioned and unlesioned animals, again in region-specific ways above and below the lesion site. A role for 5-HT in promoting recovery was suggested by the potential for improvement in locomotor activity when 5-HT was applied to poorly recovered animals, and by the consistent failure of animals to recover when they were incubated in PCPA to deplete 5-HT. However, PCPA did not affect swimming in animals that had already recovered, suggesting a difference in 5-HT effects after lesioning. These results show changes in 5-HT modulation and cellular and synaptic properties after recovery from a spinal cord transection. Importantly, effects are not confined to the sub-lesion spinal cord but also occur above the lesion site. This suggests that the changes may not simply reflect compensatory responses to the loss of descending inputs, but reflect the need for co-ordinated changes above and below the lesion site. The changes in modulatory effects should be considered in pharmacological approaches to functional recovery, as assumptions based on effects in the unlesioned spinal cord may not be justified.

Understanding effects on excitability of simulated I h modulation in simple neuronal models

The hyperpolarization-activated, inward, mixed cation current, I (h), appears in a wide variety of cells in the nervous system, contributes to diverse neuronal properties, and is up-regulated by a number of important neurotransmitters. Up-regulation of I (h) is usually associated with an excitability-enhancing depolarization of resting membrane potential and an excitability-depressing shunting effect caused by a decrease in input resistance. In order to gain a better understanding of the interaction of these effects and their influence on excitability with I (h) modulation, we systematically analyze changes in neuronal properties associated with excitability during I (h) modulation in simplified, yet, biophysical neuron models based on a hippocampal pyramidal neuron. We simulate I (h) modulation by varying both its maximal conductance and its half-activation voltage, mimicking the effects of cAMP-linked neurotransmitters, through ranges of physiologically realistic parameter regimes. Of particular interest is the contribution of the different effects of I (h) up-regulation when membrane potentials are held at common levels and neuronal excitability is probed. Our modeling results suggest that, although holding potentials at common levels may compensate for changes in resting membrane potentials, this protocol may exaggerate the excitability-depressing influences of changes in input resistances with I (h) up-regulation.

Chronic hypoxia suppresses the CO2 response of solitary complex (SC) neurons from rats

We studied the effect of chronic hypobaric hypoxia (CHx; 10-11% O(2)) on the response to hypercapnia (15% CO(2)) of individual solitary complex (SC) neurons from adult rats. We simultaneously measured the intracellular pH and firing rate responses to hypercapnia of SC neurons in superfused medullary slices from control and CHx-adapted adult rats using the blind whole cell patch clamp technique and fluorescence imaging microscopy. We found that CHx caused the percentage of SC neurons inhibited by hypercapnia to significantly increase from about 10% up to about 30%, but did not significantly alter the percentage of SC neurons activated by hypercapnia (50% in control vs. 35% in CHx). Further, the magnitudes of the responses of SC neurons from control rats (chemosensitivity index for activated neurons of 166+/-11% and for inhibited neurons of 45+/-15%) were the same in SC neurons from CHx-adapted rats. This plasticity induced in chemosensitive SC neurons by CHx appears to involve intrinsic changes in neuronal properties since they were the same in synaptic blockade medium.

Modelling Cortical Representations

Event Abstract Back to Event Modelling Cortical Representations Klaus Obermayer1* 1 Technische Universitaet, Bernstein Center for Computational Neuroscience, Germany In my talk I will first present results from a map model of primary visual cortex, where we analysed how much evidence recent single unit recordings from cat area 17 provide for a particular cortical "operating point". Using a Bayesian analysis we find, that the experimental data most strongly support a regime where the local cortical network provides dominant excitatory and inhibitory recurrent inputs (compared to the feedforward drive). Most interestingly, the data supports an operating regime which is close to the border to instability, where cortical responses are sensitive to small changes in neuronal properties. Secondly, I will show results of a study where we investigated visual attention in humans in a probabilistic reward-based visual discrimination task. We find that behavioural performance is not optimal but consistent with a heuristic based on a moving average estimate of stimulus predictability and reward. We also found that the amplitudes of early visual, attention-related EEG signals quantitatively reflect these estimates. Thus, information about stimulus statistics and reward are already integrated by low-level attentional mechanisms. Finally, I will discuss results of developmental perturbations imposed on the visual system through retinal lesions in adolescent cats. Using a computational model of visual cortical responses, I will show that the lesion induced changes of neuronal response properties are consistent with spike timing-dependent plasticity (STDP) learning rules. STDP causes visual cortical receptive fields to converge by creating a competition between neurons for the control of spike timing within the network. The spatial scale of this competition appears to depend on the balance of excitation and inhibition and and can in principle be controlled by synaptic scaling type mechanisms. Conference: Bernstein Conference on Computational Neuroscience, Frankfurt am Main, Germany, 30 Sep - 2 Oct, 2009. Presentation Type: Oral Presentation Topic: Sensory processing Citation: Obermayer K (2009). Modelling Cortical Representations. Front. Comput. Neurosci. Conference Abstract: Bernstein Conference on Computational Neuroscience. doi: 10.3389/conf.neuro.10.2009.14.129 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 27 Aug 2009; Published Online: 27 Aug 2009. * Correspondence: Klaus Obermayer, Technische Universitaet, Bernstein Center for Computational Neuroscience, 82152 Planegg-Martinsried, Germany, oby@cs.tu-berlin.de Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Klaus Obermayer Google Klaus Obermayer Google Scholar Klaus Obermayer PubMed Klaus Obermayer Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Effects of all- trans-retinoic acid on human SH-SY5Y neuroblastoma as in vitro model in neurotoxicity research

Human neuroblastoma SH-SY5Y is a dopaminergic neuronal cell line which has been used as an in vitro model for neurotoxicity experiments. Although the neuroblastoma is usually differentiated by all- trans-retinoic acid (RA), both RA-differentiated and undifferentiated SH-SY5Y cells have been used in neuroscience research. However, the changes in neuronal properties triggered by RA as well as the subsequent responsiveness to neurotoxins have not been comprehensively studied. Therefore, we aim to re-evaluate the differentiation property of RA on this cell line. We hypothesize that modulation of signaling pathways and neuronal properties during RA-mediated differentiation in SH-SY5Y cells can affect their susceptibility to neurotoxins. The differentiation property of RA was confirmed by showing an extensive outgrowth of neurites, increased expressions of neuronal nuclei, neuron specific enolase, synaptophysin and synaptic associated protein-97, and decreased expression of inhibitor of differentiation-1. While undifferentiated SH-SY5Y cells were susceptible to 6-OHDA and MPP +, RA-differentiation conferred SH-SY5Y cells higher tolerance, potentially by up-regulating survival signaling, including Akt pathway as inhibition of Akt removed RA-induced neuroprotection against 6-OHDA. As a result, the real toxicity cannot be revealed in RA-differentiated cells. Therefore, undifferentiated SH-SY5Y is more appropriate for studying neurotoxicity or neuroprotection in experimental Parkinson's disease research.

Possible Exploitation of Non-Neuronal and Non-Chemical Synaptic Signalling Pathways in Epilepsy Therapy

Although approximately 1% of the human population suffers from epilepsy, the cellular basis of this disease remains largely unresolved, and about 30% of all epilepsies are refractory to therapies using currently available drugs. Until recently, synchronous neuronal activity during seizures has been thought to be, entirely of neuronal origin, and the main stream of epilepsy research has focused on changes in membrane properties of neurons and on classical chemical neurotransmission between them. However, recent discoveries about neuron-astrocyte bidirectional communication strongly challenge this concept. These functions of astrocyte are proving significant in the understanding of epilepsy, stroke and many other neurological diseases. In addition, the most important function reported for gap junctional communication in the nervous system is the increased synchronous activity of the coupled cells. Based on the emergent evidence, it is likely that gap junctional communication plays a definite role in the associated neuronal/astrocytic networks being involved in the generation and propagation of seizure discharges in the epileptic brain. Therefore astrocytes and gap junctions as potentially new cellular targets may open new perspectives for targeted molecular therapeutic interventions and allow the development of new antiepileptic as well as anticonvulsant drugs.

Young Children Do Not Integrate Visual and Haptic Form Information

Several studies have shown that adults integrate visual and haptic information (and information from other modalities) in a statistically optimal fashion, weighting each sense according to its reliability [1, 2]. When does this capacity for crossmodal integration develop? Here, we show that prior to 8 years of age, integration of visual and haptic spatial information is far from optimal, with either vision or touch dominating totally, even in conditions in which the dominant sense is far less precise than the other (assessed by discrimination thresholds). For size discrimination, haptic information dominates in determining both perceived size and discrimination thresholds, whereas for orientation discrimination, vision dominates. By 8-10 years, the integration becomes statistically optimal, like adults. We suggest that during development, perceptual systems require constant recalibration, for which cross-sensory comparison is important. Using one sense to calibrate the other precludes useful combination of the two sources.

Astroglial Glutamate–Glutamine Shuttle Is Involved in Central Sensitization of Nociceptive Neurons in Rat Medullary Dorsal Horn

Growing evidence suggests that astroglia are involved in pain states, but no studies have tested their possible involvement in modulating the activity of nociceptive neurons per se. This study has demonstrated that the central sensitization induced in functionally identified nociceptive neurons in trigeminal subnucleus caudalis (the medullary dorsal horn) by application of an inflammatory irritant to the rat's tooth pulp can be significantly attenuated by continuous intrathecal superfusion of methionine sulfoximine (MSO; 0.1 mM), an inhibitor of the astroglial enzyme glutamine synthetase that is involved in the glutamate-glutamine shuttle. Simultaneous superfusion of MSO and glutamine (0.25 mM) restored the irritant-induced central sensitization. In control experiments, superfusion of either MSO or glutamine alone, or vehicle, did not produce any significant changes in neuronal properties. These findings suggest that the astroglial glutamate-glutamine shuttle is essential for the initiation of inflammation-induced central sensitization but that inhibition of astroglial function may not affect normal nociceptive processing.