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Neuroscience: CNS disease, pain, brain research, ion channels, synaptic transmission, channelopathies, neuronal network
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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

Julien Hering, PhD's insight:

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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HCN and KV7 (M-) channels as targets for epilepsy treatment

HCN and KV7 (M-) channels as targets for epilepsy treatment | Neuroscience_topics | Scoop.it

Voltage-gated ion channels are important determinants of cellular excitability. The Hyperpolarization-activated Cyclic Nucleotide-gated (HCN) and KV7 (M-) channels are voltage-gated ion channels. Both channels are activated at sub-threshold potentials and have biophysical properties that mirror each other. KV7 channels inhibit neuronal excitability. Thus, mutations in KV7 channels that are associated with Benign Familial Neonatal Convulsions (BFNC) are likely to be epileptogenic. Mutations in HCN channels have also been associated with idiopathic epilepsies such as GEFS+. In addition, HCN channel expression and function are modulated during symptomatic epilepsies such as temporal lobe epilepsy. It is, though, unclear as to whether the changes in HCN channel expression and function associated with the various forms of epilepsy promote epileptogenesis or are adaptive. In this review, we discuss this as well as the potential for KV7 and HCN channels as drug targets for the treatment of epilepsy. (...) - by Shah MM et al., NeuropharmacologyVolume 69, June 2013, Pages 75–81

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Jose Santos's curator insight, May 23, 2013 7:16 PM

well written.

Janys Venne's curator insight, October 25, 2013 11:01 PM


I'll appreciate your time & help to visit my website on #seizures #epilepsy at http://seizures.dolyan.com/. Thank you :)

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- Biophysical mechanisms regulating AMPA receptor accumulation at synapses

- Biophysical mechanisms regulating AMPA receptor accumulation at synapses | Neuroscience_topics | Scoop.it
Controlling the number of AMPA receptors at synapses is fundamental for fast synaptic transmission as well as for long term adaptations in synaptic strength. In this review, we examine the biophysical mechanisms implicated in regulating AMPAR levels at the cell surface and at synapses. We first describe the structure and function of AMPARs, as well as their interactions with various proteins regulating their traffic and function. Second we review the vesicular trafficking mechanism involving exocytosis and endocytosis, by which AMPARs reach the cell surface and are internalized, respectively. Third, we examine the properties of lateral diffusion of AMPARs and their trapping at post-synaptic densities. Finally, we discuss how these two parallel mechanisms are integrated in time and space to control changes in synaptic AMPAR levels in response to plasticity protocols. This review highlights the important role of the extra-synaptic AMPAR pool, which makes an obligatory link between vesicular trafficking and trapping or release at synapses. - By Czondor k & Thoumine O, Brain Research BulletinVolume 93, April 2013, Pages 57–68
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Brain mapping reveals neurological basis of decision-making in rats

Brain mapping reveals neurological basis of decision-making in rats | Neuroscience_topics | Scoop.it

Scientists at UC San Francisco have discovered how memory recall is linked to decision-making in rats, showing that measurable activity in one part of the brain occurs when rats in a maze are playing out memories that help them decide which way to turn. The more they play out these memories, the more likely they are to find their way correctly to the end of the maze. (...) - by UCSF, ScienceBlog

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12 talks on understanding the brain

12 talks on understanding the brain | Neuroscience_topics | Scoop.it

[Videos] Read Montague is interested in the human dopamine system -- or, as he puts it in this illuminating talk from TEDGlobal 2012, that which makes us "chase sex, food and salt" and therefore survive. (...) - by Kate Torgovnick, TED blog, September 24, 2012

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Brain spikes: Synchrony may be key to cracking brain's neural code

Brain spikes: Synchrony may be key to cracking brain's neural code | Neuroscience_topics | Scoop.it

In a perspective article published in the journal Nature Neuroscience on Feb. 25, 2013, biomedical engineering professor Garrett Stanley detailed research progress toward "reading and writing the neural code." This encompasses the ability to observe the spiking activity of neurons in response to outside stimuli and make clear predictions about what is being seen, heard, or felt, and the ability to artificially introduce activity within the brain that enables someone to see, hear, or feel something that is not experienced naturally through sensory organs.(...) - Science Dailay, March 12, 2013tti

Julien Hering, PhD's insight:

Journal Reference:


Garrett B Stanley. Reading and writing the neural code.Nature Neuroscience, 2013; 16 (3): 259 DOI:10.1038/nn.3330

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A comparative analysis of models of Na+ channel gating for mammalian and invertebrate nonmyelinated axons: Relationship to energy efficient action potentials

A comparative analysis of models of Na+ channel gating for mammalian and invertebrate nonmyelinated axons: Relationship to energy efficient action potentials | Neuroscience_topics | Scoop.it

The rapidly activating, voltage gated Na+ current, INa, has recently been measured in mammalian nonmyelinated axons. Those results have been incorporated in simulations of the action potential, results that demonstrate a significant separation in time during the spike between INa and the repolarizing K+ current,IK. The original Hodgkin and Huxley (1952) model of Na+ channel gating, m3h, where m and h are channel activation and inactivation, respectively, has been used in this analysis. This model was originally developed for invertebrate nonmyelinated axons, squid giant axons in particular. The model has not survived challenges based on results from invertebrate preparations using a double-step voltage clamp protocol and measurements of gating currents, results that demonstrate a kinetic link between activation and inactivation leading to a delayed onset of inactivation following a voltage step. These processes are independent of each other in the Hodgkin and Huxley (1952) model. Application of the double-step protocol to the m3h model for mammalian INa results reveals a surprising prediction, an apparent delay in onset of inactivation even though activation and inactivation are uncoupled in the model. (...) The information obtained will be significant in determining the way in which the Na+ channel is sequestered away from its open state during repolarization, thereby allowing for a separation in time between INa and IK during a spike, an energetically efficient mechanism of neuronal signaling in the mammalian brain. (...) by John R. ClayProgress in Biophysics and Molecular BiologyVolume 111, Issue 1, January 2013, Pages 1–7

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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

Julien Hering, PhD's insight:

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)

Julien Hering, PhD's insight:

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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The axon as a unique computational unit in neurons

The axon as a unique computational unit in neurons | Neuroscience_topics | Scoop.it

[Review] In the mammalian cortex, axons are highly ramified and link an enormous number of neurons over large distances. The conventional view assumes that action potentials (APs) are initiated at the axon initial segment in an all-or-none fashion and are then self-propagated orthodromically along axon collaterals without distortion of the AP waveform. By contrast, recent experimental results suggest that the axonal AP waveform can be modified depending on the activation states of the ion channels and receptors on axonal cell membranes. This AP modulation can regulate neurotransmission to postsynaptic neurons. In addition, the latest studies have provided evidence that cortical axons can integrate somatic burst firings and promote activity-dependent ectopic AP generation, which may underlie the oscillogenesis of fast rhythmic network activity. These seminal observations indicate that axons can perform diverse functional operations that extend beyond the prevailing model of axon physiology. (...) - by Sasaki TNeuroscience ResearchVolume 75, Issue 2, February 2013, Pages 83–88

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[Review] Presynaptic NMDA receptors: Are they dendritic receptors in disguise?

[Review] Presynaptic NMDA receptors: Are they dendritic receptors in disguise? | Neuroscience_topics | Scoop.it

The N-methyl-d-aspartate (NMDA) receptor plays an essential role in excitatory transmission, synaptic integration, and learning and memory. In the classical view, postsynaptic NMDA receptors act as canonical coincidence detectors providing a ‘molecular switch’ for the induction of various forms of short- and long-term synaptic plasticity. Over the past twenty years there has been accumulating evidence to suggest that NMDA receptors are also expressed presynaptically and are involved in the regulation of synaptic transmission and specific forms of activity-dependent plasticity in developing neural circuits. However, the existence of presynaptic NMDA receptors remains a contentious issue. In this review, I will discuss the criteria required for identifying functional presynaptic receptors, novel methods for probing NMDA receptor function, and recent evidence to suggest that NMDA receptors are expressed at presynaptic sites in a target-specific manner. (...) - by Duguid ICBrain Research BulletinVolume 93, April 2013, Pages 4–9

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Major Discovery For Alzheimer\'s Disease

Major Discovery For Alzheimer\'s Disease | Neuroscience_topics | Scoop.it

The Journal of Neuroscience has published a study led by researchers at the Max Planck Florida Institute for Neuroscience, the first and only U.S. extension of the prestigious Max Planck Society, that may hold a stunning breakthrough in the fight to treat Alzheimer's disease. The study potentially identifies a cause of Alzheimer's disease - based on a newly-discovered signaling pathway in cellular models of Alzheimer's disease - and opens the door for new treatments by successfully blocking this pathway. The Institute, which recently opened in December 2012, focuses solely on basic neuroscience research that aims to analyze, map, and decode the human brain - the most important and least understood organ in the body.(...)

The MPFI research indicates that the presence of Amyloid beta triggers increased levels of a signaling protein, called centaurin-alpha1 (CentA1), that appears to cause neuronal dysfunction - a potentially groundbreaking discovery that uncovers an important intermediary step in the progression of the disease. 
As part of the research, the scientists were able to identify CentA1 and measure its negative effects on neurons. Utilizing an RNA silencing technique, they turned down the cellular production of CentA1, and showed that affected neurons, exposed to Amyloid beta and exhibiting Alzheimer's related symptoms, returned to normal morphology and synaptic function, even with the continued presence of Amyloid beta. They further found that increased CentA1 activates a series of proteins, and these proteins form a signaling pathway from CentA1 to neuronal dysfunction. Thus, inhibiting other proteins in the pathway also "cured" affected neurons. (...) - Medical News Today, 21 March, 2013

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Learning and reconsolidation implicate different synaptic mechanisms

Learning and reconsolidation implicate different synaptic mechanisms | Neuroscience_topics | Scoop.it

Synaptic mechanisms underlying memory reconsolidation after retrieval are largely unknown. Here we report that synapses in projections to the lateral nucleus of the amygdala implicated in auditory fear conditioning, which are potentiated by learning, enter a labile state after memory reactivation, and must be restabilized through a postsynaptic mechanism implicating the mammalian target of rapamycin kinase-dependent signaling. Fear-conditioning–induced synaptic enhancements were primarily presynaptic in origin. Reconsolidation blockade with rapamycin, inhibiting mammalian target of rapamycin kinase activity, suppressed synaptic potentiation in slices from fear-conditioned rats. Surprisingly, this reduction of synaptic efficacy was mediated by post- but not presynaptic mechanisms. These findings suggest that different plasticity rules may apply to the processes underlying the acquisition of original fear memory and postreactivational stabilization of fear-conditioning–induced synaptic enhancements mediating fear memory reconsolidation. - by Li Y. et al., PNASvol. 110 no. 12, 47984803


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Trends in Pharmacological Sciences - From antipsychotic to anti-schizophrenia drugs: role of animal models

Trends in Pharmacological Sciences - From antipsychotic to anti-schizophrenia drugs: role of animal models | Neuroscience_topics | Scoop.it

[Abstract] Current drugs for treating schizophrenia are mostly variations on a theme that was started over 50 years ago. Sadly, clinical efficacy has not improved substantially over the years. We argue that both clinical and preclinical researchers have focused too much on psychosis, which is only one of the hallmarks of schizophrenia. This narrow focus has hampered the development of relevant animal models and human experimental medicine paradigms. Other fields in psychiatry, most notably in the realms of addiction and anxiety, have prospered from results obtained in parallel studies using animal models and experimental human studies. Lessons to be learned from those models and recent genetic and cognitive insights in schizophrenia can be utilized to develop better animal and human models and, potentially, novel treatment strategies. - by Geyer MA et al.Trends in Pharmacological SciencesVolume 33, Issue 10, 515-521, 17 July 2012

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Keely Contadeluci's curator insight, April 2, 2013 7:06 AM

Good for IB Bio LOA principles and ethics.

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An NMR investigation of the structure, function and role of the hERG channel selectivity filter in the long QT syndrome

An NMR investigation of the structure, function and role of the hERG channel selectivity filter in the long QT syndrome | Neuroscience_topics | Scoop.it

Highlights:

  • hERG's L622-K638 segment comprising the selectivity filter is unstructured in water.
  • This segment has the potential to perturb the lipid membrane.
  • Its membrane affinity is affected by K+ ions and drugs.
  • It is a potential target for promethazine in the ALQTS mechanism.
  • Non-specific drug–membrane interactions could play a role in the ALQTS.

(...) - by Gravel AE et al., Biochimica et Biophysica Acta (BBA) - Biomembranes, Available online 5 March 2013, In Press, Uncorrected Proof

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