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Metabotropic NMDA receptor function is required for β-amyloid–induced synaptic depression

The mechanisms by which β-amyloid (Aβ), a peptide fragment believed to contribute to Alzheimer’s disease, leads to synaptic deficits are not known. Here we find that elevated oligomeric Aβ requires ion flux-independent function of NMDA receptors (NMDARs) to produce synaptic depression. Aβ activates this metabotropic NMDAR function on GluN2B-containing NMDARs but not on those containing GluN2A. Furthermore, oligomeric Aβ leads to a selective loss of synaptic GluN2B responses, effecting a switch in subunit composition from GluN2B to GluN2A, a process normally observed during development. Our results suggest that conformational changes of the NMDAR, and not ion flow through its channel, are required for Aβ to produce synaptic depression and a switch in NMDAR composition. This Aβ-induced signaling mediated by alterations in GluN2B conformation may be a target for therapeutic intervention of Alzheimer’s disease. (...) - by Kessels HW et al.PNASMarch 5, 2013 vol. 110 no. 104033-4038

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Neuroscience_topics
Neuroscience: CNS disease, pain, brain research, ion channels, synaptic transmission, channelopathies, neuronal network
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Structural basis for Ca2+ selectivity of a voltage-gated calcium channel

Structural basis for Ca2+ selectivity of a voltage-gated calcium channel | Neuroscience_topics | Scoop.it

Voltage-gated calcium (CaV) channels catalyse rapid, highly selective influx of Ca2+ into cells despite a 70-fold higher extracellular concentration of Na+. How CaV channels solve this fundamental biophysical problem remains unclear. Here we report physiological and crystallographic analyses of a calcium selectivity filter constructed in the homotetrameric bacterial NaV channel NaVAb. Our results reveal interactions of hydrated Ca2+ with two high-affinity Ca2+-binding sites followed by a third lower-affinity site that would coordinate Ca2+ as it moves inward. At the selectivity filter entry, Site 1 is formed by four carboxyl side chains, which have a critical role in determining Ca2+ selectivity. Four carboxyls plus four backbone carbonyls form Site 2, which is targeted by the blocking cations Cd2+ and Mn2+, with single occupancy. The lower-affinity Site 3 is formed by four backbone carbonyls alone, which mediate exit into the central cavity. This pore architecture suggests a conduction pathway involving transitions between two main states with one or two hydrated Ca2+ ions bound in the selectivity filter and supports a ‘knock-off’ mechanism of ion permeation through a stepwise-binding process. The multi-ion selectivity filter of our CaVAb model establishes a structural framework for understanding the mechanisms of ion selectivity and conductance by vertebrate CaV channels. (...) - by Tang et al.Nature 505, 56–61 (02 January 2014)

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Modulation of NMDA receptor at the synapse: Promising therapeutic interventions in disorders of the nervous system

Modulation of NMDA receptor at the synapse: Promising therapeutic interventions in disorders of the nervous system | Neuroscience_topics | Scoop.it

[Review] There is general agreement that excessive activation of N-methyl-D-aspartate (NMDA) receptors plays a key role in mediating at least some aspects of synaptic dysfunction in several central nervous system disorders. On this view, in the last decades, research focused on the discovery of different compounds able to reduce NMDA receptor activity, such as classical and/or subunit-specific antagonists. However, the increasing body of knowledge on specific signaling pathways downstream NMDA receptors led to the identification of new pharmacological targets for NMDA receptor-related pathological conditions. Moreover, besides over-activation, several studies indicated that also abnormal NMDA receptor trafficking, resulting in the modification of the receptor subunit composition at the synapse, has a major role in the pathogenesis of several brain disorders. For this reason, the discovery of the molecular mechanisms regulating the abundance of synaptic versus extra-synaptic NMDA receptors as well as the activation of the specific signaling pathways downstream the different NMDA receptor subtypes is needed for the development of novel therapeutic approaches for NMDA receptor-dependent synaptic dysfunction. (...) - Mellone M. & Gardoni FEuropean Journal of Pharmacology

Volume 719, Issues 1–3, 5 November 2013, Pages 75–83

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Choosing an animal model for the study of Huntington's disease

Since the identification of the causative gene in Huntington's disease (HD), a number of animal models of this disorder have been developed. A frequently asked question is: which of these models most closely recapitulates the human disease? In this Review, we provide an overview of the currently available animal models of HD in the context of the clinical features of the disease. In doing so, we highlight their strengths and limitations for modelling specific symptoms of the disease. This should highlight the animal model that is best suited to address a particular question of interest and, ultimately, to expedite the discovery of treatments that will prevent or slow the progression of HD. - by Pouladi MA et al.Nature Reviews Neuroscience 14, 708–721 (2013) 

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Neuroscience thinks big (and collaboratively)

Despite cash-strapped times for research, several ambitious collaborative neuroscience projects have attracted large amounts of funding and media attention. In Europe, the Human Brain Project aims to develop a large-scale computer simulation of the brain, whereas in the United States, the Brain Activity Map is working towards establishing a functional connectome of the entire brain, and the Allen Institute for Brain Science has embarked upon a 10-year project to understand the mouse visual cortex (the MindScope project). US President Barack Obama's announcement of the BRAIN Initiative (Brain Research through Advancing Innovative Neurotechnologies Initiative) in April 2013 highlights the political commitment to neuroscience and is expected to further foster interdisciplinary collaborations, accelerate the development of new technologies and thus fuel much needed medical advances. In this Viewpoint article, five prominent neuroscientists explain the aims of the projects and how they are addressing some of the questions (and criticisms) that have arisen. - by Kandel ER et al.Nature Reviews Neuroscience 14, 659–664 (2013) 

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Water molecules control inactivation and recovery of potassium channels

Water molecules control inactivation and recovery of potassium channels | Neuroscience_topics | Scoop.it

Just 12 molecules of water cause the long post-activation recovery period required by potassium ion channels before they can function again. Using molecular simulations that modeled a potassium channel and its immediate cellular environment, atom for atom, University of Chicago scientists have revealed this new mechanism in the function of a nearly universal biological structure, with implications ranging from fundamental biology to the design of pharmaceuticals. (...) - ScienceDaily, July 28, 2013

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Acid-sensing ion channels in pain and disease

Acid-sensing ion channels in pain and disease | Neuroscience_topics | Scoop.it

Why do neurons sense extracellular acid? In large part, this question has driven increasing investigation on acid-sensing ion channels (ASICs) in the CNS and the peripheral nervous system for the past two decades. Significant progress has been made in understanding the structure and function of ASICs at the molecular level. Studies aimed at clarifying their physiological importance have suggested roles for ASICs in pain, neurological and psychiatric disease. This Review highlights recent findings linking these channels to physiology and disease. In addition, it discusses some of the implications for therapy and points out questions that remain unanswered. (...) - by Wemmie JA et al., Nature Reviews Neuroscience 14, 461–471 (2013)

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NMDA receptor subunit diversity: impact on receptor properties, synaptic plasticity and disease

NMDA receptor subunit diversity: impact on receptor properties, synaptic plasticity and disease | Neuroscience_topics | Scoop.it

NMDA receptors (NMDARs) are glutamate-gated ion channels and are crucial for neuronal communication. NMDARs form tetrameric complexes that consist of several homologous subunits. The subunit composition of NMDARs is plastic, resulting in a large number of receptor subtypes. As each receptor subtype has distinct biophysical, pharmacological and signalling properties, there is great interest in determining whether individual subtypes carry out specific functions in the CNS in both normal and pathological conditions. Here, we review the effects of subunit composition on NMDAR properties, synaptic plasticity and cellular mechanisms implicated in neuropsychiatric disorders. Understanding the rules and roles of NMDAR diversity could provide new therapeutic strategies against dysfunctions of glutamatergic transmission - by Pierre PaolettiCamilla Bellone Qiang Zhou, Nature Reviews Neuroscience 14, 383–400 (2013)

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Where no synapses go: gatekeepers of circuit remodeling and synaptic strength

Where no synapses go: gatekeepers of circuit remodeling and synaptic strength | Neuroscience_topics | Scoop.it

Growth inhibitory molecules in the adult mammalian central nervous system (CNS) have been implicated in the blocking of axonal sprouting and regeneration following injury. Prominent CNS regeneration inhibitors include Nogo-A, oligodendrocyte myelin glycoprotein (OMgp), and chondroitin sulfate proteoglycans (CSPGs), and a key question concerns their physiological role in the naïve CNS. Emerging evidence suggests novel functions in dendrites and at synapses of glutamatergic neurons. CNS regeneration inhibitors target the neuronal actin cytoskeleton to regulate dendritic spine maturation, long-term synapse stability, and Hebbian forms of synaptic plasticity. This is accomplished in part by antagonizing plasticity-promoting signaling pathways activated by neurotrophic factors. Altered function of CNS regeneration inhibitors is associated with mental illness and loss of long-lasting memory, suggesting unexpected and novel physiological roles for these molecules in brain health. - by Mironova Y & Giger RJ, Trends in NeurosciencesVolume 36, Issue 6, June 2013, Pages 363–373

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The Cav3–Kv4 Complex Acts as a Calcium Sensor to Maintain Inhibitory Charge Transfer during Extracellular Calcium Fluctuations

Synaptic transmission and neuronal excitability depend on the concentration of extracellular calcium ([Ca]o), yet repetitive synaptic input is known to decrease [Ca]oin numerous brain regions. In the cerebellar molecular layer, synaptic input reduces [Ca]o by up to 0.4 mM in the vicinity of stellate cell interneurons and Purkinje cell dendrites. The mechanisms used to maintain network excitability and Purkinje cell output in the face of this rapid change in calcium gradient have remained an enigma. Here we use single and dual patch recordings in an in vitro slice preparation of Sprague Dawley rats to investigate the effects of physiological decreases in [Ca]o on the excitability of cerebellar stellate cells and their inhibitory regulation of Purkinje cells. We find that a Cav3–Kv4 ion channel complex expressed in stellate cells acts as a calcium sensor that responds to a decrease in [Ca]o by dynamically adjusting stellate cell output to maintain inhibitory charge transfer to Purkinje cells. The Cav3–Kv4 complex thus enables an adaptive regulation of inhibitory input to Purkinje cells during fluctuations in [Ca]o, providing a homeostatic control mechanism to regulate Purkinje cell excitability during repetitive afferent activity. (...) - by Anderson D & Engbers JDT et al.The Journal of Neuroscience, 1 May 2013, 33(18): 7811-7824

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Ligand-Gating by Ca2+ Is Rate Limiting for Physiological Operation of BKCa Channels

Large conductance Ca2+- and voltage-activated potassium channels (BKCa) shape neuronal excitability and signal transduction. This reflects the integrated influences of transmembrane voltage and intracellular calcium concentration ([Ca2+]i) that gate the channels. This dual gating has been mainly studied as voltage-triggered gating modulated by defined steady-state [Ca2+]i, a paradigm that does not approximate native conditions. Here we use submillisecond changes of [Ca2+]i to investigate the time course of the Ca2+-triggered gating of BKCa channels expressed in Chinese hamster ovary cells at distinct membrane potentials in the physiological range. The results show that Ca2+ can effectively gate BKCa channels and that Ca2+ gating is largely different from voltage-driven gating. Most prominently, Ca2+ gating displays a pronounced delay in the millisecond range between Ca2+ application and channel opening (pre-onset delay) and exhibits slower kinetics across the entire [Ca2+]i-voltage plane. Both characteristics are selectively altered by co-assembled BKβ4 or an epilepsy-causing mutation that either slows deactivation or speeds activation and reduces the pre-onset delay, respectively. Similarly, co-assembly of the BKCachannels with voltage-activated Ca2+ (Cav) channels, mirroring the native configuration, decreased the pre-onset delay to submillisecond values. In BKCa–Cav complexes, the time course of the hyperpolarizing K+-current response is dictated by the Ca2+ gating of the BKCa channels. Consistent with Cav-mediated Ca2+ influx, gating was fastest at hyperpolarized potentials, but decreased with depolarization of the membrane potential. Our results demonstrate that under experimental paradigms meant to approximate the physiological conditions BKCa channels primarily operate as ligand-activated channels gated by intracellular Ca2+ and that Ca2+ gating is tuned for fast responses in neuronal BKCa–Cav complexes. - by Berkefeld H & Fakler B, The Journal of Neuroscience, 24 April 2013, 33(17): 7358-7367

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The BKca channels are directly tuned by intracellular calcium binding. These channels are fast-operated by variation of intracellular calcium in physiological conditions through the BKca-Cav complexes.

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A Model of Functional Brain Connectivity and Background Noise as a Biomarker for Cognitive Phenotypes: Application to Autism

A Model of Functional Brain Connectivity and Background Noise as a Biomarker for Cognitive Phenotypes: Application to Autism | Neuroscience_topics | Scoop.it

We present an efficient approach to discriminate between typical and atypical brains from macroscopic neural dynamics recorded as magnetoencephalograms (MEG). Our approach is based on the fact that spontaneous brain activity can be accurately described with stochastic dynamics, as a multivariate Ornstein-Uhlenbeck process (mOUP). By fitting the data to a mOUP we obtain: 1) the functional connectivity matrix, corresponding to the drift operator, and 2) the traces of background stochastic activity (noise) driving the brain. We applied this method to investigate functional connectivity and background noise in juvenile patients (n = 9) with Asperger’s syndrome, a form of autism spectrum disorder (ASD), and compared them to age-matched juvenile control subjects (n = 10). Our analysis reveals significant alterations in both functional brain connectivity and background noise in ASD patients. The dominant connectivity change in ASD relative to control shows enhanced functional excitation from occipital to frontal areas along a parasagittal axis. Background noise in ASD patients is spatially correlated over wide areas, as opposed to control, where areas driven by correlated noise form smaller patches. An analysis of the spatial complexity reveals that it is significantly lower in ASD subjects. Although the detailed physiological mechanisms underlying these alterations cannot be determined from macroscopic brain recordings, we speculate that enhanced occipital-frontal excitation may result from changes in white matter density in ASD, as suggested in previous studies. We also venture that long-range spatial correlations in the background noise may result from less specificity (or more promiscuity) of thalamo-cortical projections. All the calculations involved in our analysis are highly efficient and outperform other algorithms to discriminate typical and atypical brains with a comparable level of accuracy. Altogether our results demonstrate a promising potential of our approach as an efficient biomarker for altered brain dynamics associated with a cognitive phenotype. (...) - by Dominguer LG et al., PLoS ONE 8(4): e61493

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Drug-evoked synaptic plasticity: beyond metaplasticity

Drug-evoked synaptic plasticity: beyond metaplasticity | Neuroscience_topics | Scoop.it
  • Addictive drugs alter synaptic plasticity in the VTA through a common mechanism.
  • Changes in the VTA are permissive for later mesocorticolimbic circuit remodeling.
  • Mesocorticolimbic circuit remodeling may underlie addiction-related behaviors.
  • Reversing drug-induced plasticity may ultimately suppress addiction-related behavior.

by Creed MC & Lüscher C, Current Opinion in Neurobiology, online 6 April 2013

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Adenosine receptors as drug targets - what are the challenges?

[Review] Adenosine signalling has long been a target for drug development, with adenosine itself or its derivatives being used clinically since the 1940s. In addition, methylxanthines such as caffeine have profound biological effects as antagonists at adenosine receptors. Moreover, drugs such as dipyridamole and methotrexate act by enhancing the activation of adenosine receptors. There is strong evidence that adenosine has a functional role in many diseases, and several pharmacological compounds specifically targeting individual adenosine receptors — either directly or indirectly — have now entered the clinic. However, only one adenosine receptor-specific agent — the adenosine A2A receptor agonist regadenoson (Lexiscan; Astellas Pharma) — has so far gained approval from the US Food and Drug Administration (FDA). Here, we focus on the biology of adenosine signalling to identify hurdles in the development of additional pharmacological compounds targeting adenosine receptors and discuss strategies to overcome these challenges.(...) - by Chen JF et al., Nature Reviews Drug Discovery, 12265-286 (April 2013)

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Neurophysiology of HCN channels: From cellular functions to multiple regulations

Neurophysiology of HCN channels: From cellular functions to multiple regulations | Neuroscience_topics | Scoop.it
Highlights
  • Hyperpolarization-activated cyclic nucleotide-gated (HCN) cation channels are involved in multiple physiological processes.
  • HCN channels are excellent targets of various cellular signals to finely regulate neuronal responses to external stimuli.
  • Dysregulation of HCN channels is involved in a variety of neurological disorders.
by He C et al.Progress in NeurobiologyVolume 112, January 2014, Pages 1–23
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An interesting review about HCN these must-known ion channels that are involved in numerous physiological processes and brain diseases.

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Ca2+ channel nanodomains boost local Ca2+ amplitude

Local Ca2+ signals drive important events like synaptic transmission, neural plasticity, and cardiac contraction, yet the fundamental relationship between flux through a single channel and the Ca2+amplitude within nanometers of the channel pore has eluded direct experimental measure. Here we reverse-engineer the problem by using Ca2+-dependent inactivation of channels as a nanometer-range biosensor of Ca2+ amplitude. We discovered an unexpected and dramatic boost in nanodomain Ca2+ amplitude, ten-fold higher than predicted on theoretical grounds. This boost in local Ca2+ signaling may act to maximize the biochemical information capacity of electrically\x{2011}active cells. - by Tadross MR, PNASvol. 110 no. 39, 1579415799


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A golden approach to ion channel inhibition

A golden approach to ion channel inhibition | Neuroscience_topics | Scoop.it

Drugs are often used in combination and, for pharmacologists, the manner of their interactions can cast light on drug mechanisms and biological processes. Here we provide simplified descriptions of commonly used analytical methods for analysing drug combinations and describe a new and practical experimental solution to address the mechanistic question: Do two channel-blocking drugs bind at the same site? We define two simple mathematical models that describe the effects of two channel blockers acting simultaneously at either the same (Syntopic Model) or different (Allotopic Model) binding sites within a channel pore. We find that the optimum concentrations of two drugs for distinguishing between the two models are related to the mathematical Golden Ratio. - by Jarvis GE & Thompson AJTrends in Pharmacological SciencesVolume 34, Issue 9, 481-488, 23 August 2013

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Control of neuronal voltage-gated calcium ion channels from RNA to protein

[Review] Highlights:
  • How many different voltage-gated calcium (CaV) channels are there and should one care?
  • All mammalian Cacna1 genes have the potential to generate hundreds of CaV channels.
  • Cell specific mechanisms control CaV channel function at RNA and protein levels according to cell type.
  • Cell specific protein–protein interactions control subcellular CaV channel trafficking and function.
  • Cell specific and subcellular expression patterns of CaV isoforms are important for disease and treatment development.

(...) - by Lipscombe D et al., Trends in Neurosciences, available online 30 July 2013

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Very long-term memories may be stored in the pattern of holes in the perineuronal net

Very long-term memories may be stored in the pattern of holes in the perineuronal net | Neuroscience_topics | Scoop.it

A hypothesis and the experiments to test it propose that very long-term memories, such as fear conditioning, are stored as the pattern of holes in the perineuronal net (PNN), a specialized ECM that envelops mature neurons and restricts synapse formation. The 3D intertwining of PNN and synapses would be imaged by serial-section EM. Lifetimes of PNN vs. intrasynaptic components would be compared with pulse-chase 15N labeling in mice and 14C content in human cadaver brains. Genetically encoded indicators and antineoepitope antibodies should improve spatial and temporal resolution of the in vivo activity of proteases that locally erode PNN. Further techniques suggested include genetic KOs, better pharmacological inhibitors, and a genetically encoded snapshot reporter, which will capture the pattern of activity throughout a large ensemble of neurons at a time precisely defined by the triggering illumination, drive expression of effector genes to mark those cells, and allow selective excitation, inhibition, or ablation to test their functional importance. The snapshot reporter should enable more precise inhibition or potentiation of PNN erosion to compare with behavioral consequences. Finally, biosynthesis of PNN components and proteases would be imaged. (...) - By Roger Y. TsienPNAS July 23, 2013 vol. 110 no. 3012456-12461

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The Mechanism of Na+/K+ Selectivity in Mammalian Voltage-Gated Sodium Channels Based on Molecular Dynamics Simulation

The Mechanism of Na+/K+ Selectivity in Mammalian Voltage-Gated Sodium Channels Based on Molecular Dynamics Simulation | Neuroscience_topics | Scoop.it

Voltage-gated sodium (Nav) channels and their Na+/K+ selectivity are of great importance in the mammalian neuronal signaling. According to mutational analysis, the Na+/K+ selectivity in mammalian Nav channels is mainly determined by the Lys and Asp/Glu residues located at the constriction site within the selectivity filter. Despite successful molecular dynamics simulations conducted on the prokaryotic Nav channels, the lack of Lys at the constriction site of prokaryotic Nav channels limits how much can be learned about the Na+/K+selectivity in mammalian Nav channels. In this work, we modeled the mammalian Nav channel by mutating the key residues at the constriction site in a prokaryotic Nav channel (NavRh) to its mammalian counterpart. By simulating the mutant structure, we found that the Na+ preference in mammalian Nav channels is collaboratively achieved by the deselection from Lys and the selection from Asp/Glu within the constriction site. - by XIA M et al., Biophysical JournalVolume 104, Issue 11, 4 June 2013, Pages 2401–2409

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[Review] Neurotransmitter Transporters: Structure Meets Function

[Review] Neurotransmitter Transporters: Structure Meets Function | Neuroscience_topics | Scoop.it
Highlights
  • Review of sodium coupling and conformational change in neurotransmitter transporter
  • Side-by-side structural comparison of transporter homologs GltPh and LeuT
  • Relating crystal structures of GltPh and LeuT to functional data and simulations
  • Structural and functional implications of sodium coupling in these transporters

(...) - by Focke PJ et al.StructureVolume 21, Issue 5, 694-705, 7 May 2013

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Altered Calcium Metabolism in Aging CA1 Hippocampal Pyramidal Neurons

Altered neuronal calcium homeostasis is widely hypothesized to underlie cognitive deficits in normal aging subjects, but the mechanisms that underlie this change are unknown, possibly due to a paucity of direct measurements from aging neurons. Using CCD and two-photon calcium imaging techniques on CA1 pyramidal neurons from young and aged rats, we show that calcium influx across the plasma membrane increases with aging, and that this change is countered by increased intracellular calcium buffering. The additional buffer in aging neurons balances the increased calcium influx following a small number (<3) action potentials, but is overwhelmed during sustained or theta-like activity which leads to a greater rise in intracellular calcium concentration in aging than that in young neurons. Our results demonstrate that calcium overload occurs regularly in aging CA1 pyramidal neurons under physiological conditions. This overload may be a critical factor in age-related decline in hippocampus-dependent cognitive function. - by Oh MM et al., The Journal of Neuroscience, 1 May 2013, 33(18): 7905-7911

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One of the pathways for age-related declined of hippocampus-dependent cogintive function is identified by the team of John Disterhoft

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Presynaptic NMDA Receptor Mechanisms for Enhancing Spontaneous Neurotransmitter Release

NMDA receptors (NMDARs) are required for experience-driven plasticity during formative periods of brain development and are critical for neurotransmission throughout postnatal life. Most NMDAR functions have been ascribed to postsynaptic sites of action, but there is now an appreciation that presynaptic NMDARs (preNMDARs) can modulate neurotransmitter release in many brain regions, including the neocortex. Despite these advances, the cellular mechanisms by which preNMDARs can affect neurotransmitter release are largely unknown. Here we interrogated preNMDAR functions pharmacologically to determine how these receptors promote spontaneous neurotransmitter release in mouse primary visual cortex. Our results provide three new insights into the mechanisms by which preNMDARs can function. First, preNMDARs can enhance spontaneous neurotransmitter release tonically with minimal extracellular Ca2+ or with major sources of intracellular Ca2+blocked. Second, lowering extracellular Na+ levels reduces the contribution of preNMDARs to spontaneous transmitter release significantly. Third, preNMDAR enhance transmitter release in part through protein kinase C signaling. These data demonstrate that preNMDARs can act through novel pathways to promote neurotransmitter release in the absence of action potentials. - by Kunz PA et al., The Journal of Neuroscience, 1 May 2013, 33(18)

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Nice study about spontaneous activity at the synapses by NMDA receptors

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[Review] Mechanisms of epileptogenesis: a convergence on neural circuit dysfunction

Epilepsy is a prevalent neurological disorder associated with significant morbidity and mortality, but the only available drug therapies target its symptoms rather than the underlying cause. The process that links brain injury or other predisposing factors to the subsequent emergence of epilepsy is termed epileptogenesis. Substantial research has focused on elucidating the mechanisms of epileptogenesis so as to identify more specific targets for intervention, with the hope of preventing epilepsy before seizures emerge. Recent work has yielded important conceptual advances in this field. We suggest that such insights into the mechanisms of epileptogenesis converge at the level of cortical circuit dysfunction. - by Goldberg EM & Coulter DANature Reviews Neuroscience 14337-349 (May 2013)

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Is Brain Mapping Ready for Big Science?

Is Brain Mapping Ready for Big Science? | Neuroscience_topics | Scoop.it

The BAM project will be an expensive undertaking. Will it be worth the cost?


President Barack Obama’s public-private initiative to create an activity map of the human brain will cost more than $3 billion, projections say, or $300 million annually for 10 years. The project has multiple private and public institutions lined up to participate, including the Defense Advanced Research Projects Agency (DARPA) and the National Science Foundation. All parties hope that the initiative will move brain science forward with the same kind of money and focused effort that drove the Genome Project. (...) - GEN News, Insight & Intelligence, by Patricia Fitzpatrick Dimond, Ph.D., Marsh 29, 2013


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Big boost in drug discovery: New use for stem cells identifies a promising way to target ALS

Big boost in drug discovery: New use for stem cells identifies a promising way to target ALS | Neuroscience_topics | Scoop.it

Using a new, stem cell-based, drug-screening technology that could reinvent and greatly reduce the cost of developing pharmaceuticals, researchers at the Harvard Stem Cell Institute (HSCI) have found a compound that is more effective in protecting the neurons killed in amyotrophic lateral sclerosis (ALS) than are two drugs that failed in human clinical trials after large sums were invested in them.

The new screening technique developed by Lee Rubin, a member of HSCI’s executive committee and a professor in Harvard’s Department of Stem Cell and Regenerative Biology (SCRB), had predicted that the two drugs that eventually failed in the third and final stage of human testing would do just that. (...) - By Joseph Caputo (Harvard Staff Writer), HarvardScience, April 18, 2013

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