Neuroscience_topics
Follow
Find
19.1K views | +7 today
Neuroscience_topics
Neuroscience: CNS disease, pain, brain research, ion channels, synaptic transmission, channelopathies, neuronal network
Your new post is loading...
Your new post is loading...
Scooped by Julien Hering, PhD
Scoop.it!

K+ pump: From caterpillar midgut to human cochlea

K+ pump: From caterpillar midgut to human cochlea | Neuroscience_topics | Scoop.it

Deafness is a serious condition that affects millions of people and can also lead to dementia. Moreover, Karet and associates reported in 1999 that mutations in the gene encoding H+ V-ATPase subunit B1 lead to deafness. Yet ionic flows that enable humans to hear high-pitched sounds at 20,000 cycles/sec (20 kHz) are not well understood. (...) Central to this model is the hypothesis that a K+ pump which secretes K+ into a K+-rich compartment is composed of a voltage producing (electrogenic) H+ V-ATPase that is electrically coupled to a voltage-driven (electrophoretic) K+/nH+ antiporter (KHA). (...) The new model proposed in the present paper could lead to important changes in our understanding of sensory physiology. - Journal of Insect Physiology 58(4), 2012

more...
No comment yet.
Scooped by Julien Hering, PhD
Scoop.it!

Neurotransmitter receptors and cognitive dysfunction in Alzheimer's disease and Parkinson's disease

Neurotransmitter receptors and cognitive dysfunction in Alzheimer's disease and Parkinson's disease | Neuroscience_topics | Scoop.it

Highlights
► Alzheimer is a multifactorial age-related neurodegenerative biological process. ► Alzheimer is distinct of normal aging by presence of neurofibrillary tangles and senile plaques. ► Alzheimer has capacities of seeding and spreading of lesions which may lead to dementia. ► Early Alzheimer changes confined to selected regions are the first grounds and the main risk factor for developing dementia. ► Early stages of Alzheimer should be considered as primary targets of therapeutic intervention in order to prevent progression to disease states. - Progress in Neurobiology 97(1), 2012

more...
No comment yet.
Scooped by Julien Hering, PhD
Scoop.it!

Ca2+-dependent regulation of synaptic vesicle endocytosis

Ca2+-dependent regulation of synaptic vesicle endocytosis | Neuroscience_topics | Scoop.it

[Review] Action potentials, when arriving at presynaptic terminals, elicit Ca2+ influx through voltage-gated Ca2+ channels. Intracellular [Ca2+] elevation around the channels subsequently triggers synaptic vesicle exocytosis and also induces various protein reactions that regulate vesicle endocytosis and recycling to provide for long-term sustainability of synaptic transmission. Recent studies using membrane capacitance measurements, as well as high-resolution optical imaging, have revealed that the dominant type of synaptic vesicle endocytosis at central nervous system synapses is mediated by clathrin and dynamin. Furthermore, Ca2+-dependent mechanisms regulating endocytosis may operate in different ways depending on the distance from Ca2+ channels: (1) intracellular Ca2+ in the immediate vicinity of a Ca2+ channel plays an essential role in triggering endocytosis, and (2) intracellular Ca2+ traveling far from the channels has a modulatory effect on endocytosis at the periactive zone. Here, I integrate the latest progress in this field to propose a compartmental model for regulation of vesicle endocytosis at synapses and discuss the possible roles of presynaptic Ca2+-binding proteins including calmodulin, calcineurin and synaptotagmin. - Neuroscience Res. 73(1), 2012

more...
No comment yet.
Scooped by Julien Hering, PhD
Scoop.it!

Memories can be turn on by stimulating brain cells: Study - Zee News

Memories can be turn on by stimulating brain cells: Study - Zee News | Neuroscience_topics | Scoop.it
Memories can be turn on by stimulating brain cells: StudyZee NewsWell, scientists at MIT claim it is possible to activate a memory on demand by stimulating only a few neurons of your brain with light.
more...
Scooped by Julien Hering, PhD
Scoop.it!

Décodage des crises épileptiques

Décodage des crises épileptiques | Neuroscience_topics | Scoop.it

L'équipe de recherche du laboratoire de neurosciences moléculaires de la " Hong Kong University of Science and Technology " a mis en évidence des propriétés révolutionnaires liées aux mécanismes de signalisation du développement du cerveau. Cette découverte pourrait avoir des implications importantes en biomédecine. - BE Chine 115 

more...
No comment yet.
Scooped by Julien Hering, PhD
Scoop.it!

Optogenetic stimulation of a hippocampal engram activates fear memory recall

Optogenetic stimulation of a hippocampal engram activates fear memory recall | Neuroscience_topics | Scoop.it

A specific memory is thought to be encoded by a sparse population of neurons1, 2. These neurons can be tagged during learning for subsequent identification3 and manipulation4, 5, 6. Moreover, their ablation or inactivation results in reduced memory expression, suggesting their necessity in mnemonic processes. However, the question of sufficiency remains: it is unclear whether it is possible to elicit the behavioural output of a specific memory by directly activating a population of neurons that was active during learning. Here we show in mice that optogenetic reactivation of hippocampal neurons activated during fear conditioning is sufficient to induce freezing behaviour. (...) Together, our findings indicate that activating a sparse but specific ensemble of hippocampal neurons that contribute to a memory engram is sufficient for the recall of that memory. Moreover, our experimental approach offers a general method of mapping cellular populations bearing memory engrams. see at 

http://www.nature.com/nature/journal/vnfv/ncurrent/full/nature11028.html

more...
No comment yet.
Scooped by Julien Hering, PhD
Scoop.it!

Figuring Out How a Metabotropic Glutamate Receptor Affects Mental Health

Figuring Out How a Metabotropic Glutamate Receptor Affects Mental Health | Neuroscience_topics | Scoop.it

Metabotropic glutamate receptors (mGluRs) are implicated in brain disorders that involve the prefrontal cortex, the part of the brain that is important for cognitive and emotional processes. A potential target of mGluRs is the NMDA glutamate receptor (NMDAR). Malfunctions in NMDAR regulation are associated with schizophrenia and other mental illnesses. In this Paper of the Week, Zhen Yan and colleagues at the State University of New York at Buffalo looked at how one particular type of mGluR, called mGluR7, interacted with NMDAR. mGluR7 has a very low affinity for glutamate and is activated only in conditions associated with diseases. The investigators discovered that mGluR7 inhibits NMDAR function by affecting actin dynamics and decreasing NMDARs at the synapses. The authors say their data suggest a mechanism by which mGluR7 regulates prefrontal cortex activities and that the receptor could be a target in treating mental disorders. - JBC 287, 2012

more...
No comment yet.
Scooped by Julien Hering, PhD
Scoop.it!

The ageing cortical synapse: hallmarks and implications for cognitive decline

[Review] Normal ageing is associated with impairments in cognitive function, including memory. These impairments are linked, not to a loss of neurons in the forebrain, but to specific and relatively subtle synaptic alterations in the hippocampus and prefrontal cortex. Here, we review studies that have shed light on the cellular and synaptic changes observed in these brain structures during ageing that can be directly related to cognitive decline in young and aged animals. We also discuss the influence of the hormonal status on these age-related alterations and recent progress in the development of therapeutic strategies to limit the impact of ageing on memory and cognition in humans. - Nature Rev Neuroscience 13, 2012

more...
No comment yet.
Scooped by Julien Hering, PhD
Scoop.it!

GPCR mediated regulation of synaptic transmission

GPCR mediated regulation of synaptic transmission | Neuroscience_topics | Scoop.it

[Review] Synaptic transmission is a finely regulated mechanism of neuronal communication. The release of neurotransmitter at the synapse is not only the reflection of membrane depolarization events, but rather, is the summation of interactions between ion channels, G protein coupled receptors, second messengers, and the exocytotic machinery itself which exposes the components within a synaptic vesicle to the synaptic cleft. The focus of this review is to explore the role of G protein signaling as it relates to neurotransmission, as well as to discuss the recently determined inhibitory mechanism of Gβγ dimers acting directly on the exocytotic machinery proteins to inhibit neurotransmitter release. - Progress in Neurobiology 96(3), 2012

more...
No comment yet.
Scooped by Julien Hering, PhD
Scoop.it!

Conus Venom Peptide Pharmacology

Conus Venom Peptide Pharmacology | Neuroscience_topics | Scoop.it

[Review] Conopeptides are a diverse group of recently evolved venom peptides used for prey capture and/or defense. Each species of cone snails produces in excess of 1000 conopeptides, with those pharmacologically characterized (∼0.1%) targeting a diverse range of membrane proteins typically with high potency and specificity. The majority of conopeptides inhibit voltage- or ligand-gated ion channels, providing valuable research tools for the dissection of the role played by specific ion channels in excitable cells. It is noteworthy that many of these targets are found to be expressed in pain pathways, with several conopeptides having entered the clinic as potential treatments for pain [e.g., pyroglutamate1-MrIA (Xen2174)] and one now marketed for intrathecal treatment of severe pain [ziconotide (Prialt)]. This review discusses the diversity, pharmacology, structure-activity relationships, and therapeutic potential of cone snail venom peptide families acting at voltage-gated ion channels, ligand-gated ion channels, G-protein-coupled receptors, and neurotransmitter transporters, with expanded discussion on the clinical potential of sodium and calcium channel inhibitors and α-conotoxins... Pharmacological Rev.

more...
No comment yet.
Scooped by Julien Hering, PhD
Scoop.it!

Are Extrasynaptic GABAA Receptors Important Targets for Sedative/Hypnotic Drugs?

High-affinity extrasynaptic GABAA receptors are persistently activated by the low ambient GABA levels that are known to be present in extracellular space. The resulting tonic conductance generates a form of shunting inhibition that is capable of altering cellular and network behavior. It has been suggested that this tonic inhibition will be enhanced by neurosteroids, antiepileptics, and sedative/hypnotic drugs. However, we show that the ability of sedative/hypnotic drugs to enhance tonic inhibition in the mouse cerebellum will critically depend on ambient GABA levels. For example, we show that the intravenous anesthetic propofol enhances tonic inhibition only when ambient GABA levels are <100 nM. More surprisingly, the actions of the sleep-promoting drug 4,5,6,7-tetrahydroisothiazolo-[5,4-c]pyridin-3-ol (THIP) are attenuated at ambient GABA levels of just 20 nM. In contrast, our data suggest that neurosteroid enhancement of tonic inhibition will be greater at high ambient GABA concentrations. We present a model that takes into account realistic estimates of ambient GABA levels and predicted extrasynaptic GABAA receptor numbers when considering the ability of sedative/hypnotic drugs to enhance tonic inhibition. These issues will be important when considering drug strategies designed to target extrasynaptic GABAA receptors in the treatment of sleep disorders and other neurological conditions. - J. Neuroscience 32(11), 2012

more...
No comment yet.
Scooped by Julien Hering, PhD
Scoop.it!

CaMKII binding to GluN2B is critical during memory consolidation : Abstract : The EMBO Journal

CaMKII binding to GluN2B is critical during memory consolidation : Abstract : The EMBO Journal | Neuroscience_topics | Scoop.it

Memory is essential for our normal daily lives and our sense of self. Ca2+ influx through the NMDA-type glutamate receptor (NMDAR) and the ensuing activation of the Ca2+ and calmodulin-dependent protein kinase (CaMKII) are required for memory formation and its physiological correlate, long-term potentiation (LTP). The Ca2+ influx induces CaMKII binding to the NMDAR to strategically recruit CaMKII to synapses that are undergoing potentiation. We generated mice with two point mutations that impair CaMKII binding to the NMDAR GluN2B subunit. Ca2+-triggered postsynaptic accumulation is largely abrogated for CaMKII and destabilized for TARPs, which anchor AMPA-type glutamate receptors (AMPAR). LTP is reduced by 50% and phosphorylation of the AMPAR GluA1 subunit by CaMKII, which enhances AMPAR conductance, impaired. The mutant mice learn the Morris water maze (MWM) as well as WT but show deficiency in recall during the period of early memory consolidation. Accordingly, the activity-driven interaction of CaMKII with the NMDAR is important for recall of MWM memory as early as 24 h, but not 1–2 h, after training potentially due to impaired consolidation. EMBO J. 31(1203-16), 2012

more...
No comment yet.
Scooped by Julien Hering, PhD
Scoop.it!

Discovery of hair-cell roots suggests the brain modulates sound sensitivity

Discovery of hair-cell roots suggests the brain modulates sound sensitivity | Neuroscience_topics | Scoop.it
The hair cells of the inner ear have a previously unknown "root" extension that may allow them to communicate with nerve cells and the brain to regulate sensitivity to sound vibrations and head position, researchers have discovered.
more...
No comment yet.
Scooped by Julien Hering, PhD
Scoop.it!

The accuracy of membrane potential reconstruction based on spiking receptive fields

The accuracy of membrane potential reconstruction based on spiking receptive fields | Neuroscience_topics | Scoop.it

A common technique used to study the response selectivity of neurons is to measure the relationship between sensory stimulation and action potential responses. Action potentials, however, are only indirectly related to the synaptic inputs that determine the underlying, subthreshold, response selectivity. We present a method to predict membrane potential, the measurable result of the convergence of synaptic inputs, based on spike rate alone and then test its utility by comparing predictions to actual membrane potential recordings from simple cells in primary visual cortex. Using a noise stimulus, we found that spike rate receptive fields were in precise correspondence with membrane potential receptive fields (R2 = 0.74). On average, spike rate alone could predict 44% of membrane potential fluctuations to dynamic noise stimuli, demonstrating the utility of this method to extract estimates of subthreshold responses. We also found that the nonlinear relationship between membrane potential and spike rate could also be extracted from spike rate data alone by comparing predictions from the noise stimulus with the actual spike rate. Our analysis reveals that linear receptive field models extracted from noise stimuli accurately reflect the underlying membrane potential selectivity and thus represent a method to generate estimates of the underlying average membrane potential from spike rate data alone. - J. Neurophysiology 107(8), 2012

more...
No comment yet.
Scooped by Julien Hering, PhD
Scoop.it!

Neuron - Calcium-Activated Chloride Channels (CaCCs) Regulate Action Potential and Synaptic Response in Hippocampal Neurons

Neuron - Calcium-Activated Chloride Channels (CaCCs) Regulate Action Potential and Synaptic Response in Hippocampal Neurons | Neuroscience_topics | Scoop.it

Central neurons respond to synaptic inputs from other neurons by generating synaptic potentials. Once the summated synaptic potentials reach threshold for action potential firing, the signal propagates leading to transmitter release at the synapse. The calcium influx accompanying such signaling opens calcium-activated ion channels for feedback regulation. Here, we report a mechanism for modulating hippocampal neuronal signaling that involves calcium-activated chloride channels (CaCCs). We present evidence that CaCCs reside in hippocampal neurons and are in close proximity of calcium channels and NMDA receptors to shorten action potential duration, dampen excitatory synaptic potentials, impede temporal summation, and raise the threshold for action potential generation by synaptic potential. Having recently identified TMEM16A and TMEM16B as CaCCs, we further show that TMEM16B but not TMEM16A is important for hippocampal CaCC, laying the groundwork for deciphering the dynamic CaCC modulation of neuronal signaling in neurons important for learning and memory. - Neuron 74(1), 2012

more...
No comment yet.
Scooped by Julien Hering, PhD
Scoop.it!

Altered Kv3.3 channel gating in early-onset spinocerebellar ataxia type 13

• Mutations in the Kv3.3 voltage-gated potassium channel cause the human genetic disease spinocerebellar ataxia type 13.

• Depending on the mutation, the disease emerges during early childhood or during adulthood.

• Kv3.3 mutations affect channel function but previous work did not clarify the relationship between changes in channel activity and the age of disease onset.

• In this study, we showed that mutations that cause early-onset disease have similar effects on the voltage dependence and kinetics of channel opening, whereas a mutation that causes adult-onset disease reduces current amplitude but has little effect on voltage dependence or kinetics.

• We conclude that changes in channel gating contribute substantially to an early age of onset in spinocerebellar ataxia type 13. - J Physiol 590, 2012

more...
No comment yet.
Scooped by Julien Hering, PhD
Scoop.it!

Une grille en 3D du réseau de fibres dans le cerveau

Une grille en 3D du réseau de fibres dans le cerveau | Neuroscience_topics | Scoop.it

Une nouvelle étude révèle que les trajets nerveux dans le cerveau sont organisés selon une grille très ordonnée comprenant trois couches en trois dimensions. - Sciences et Avenir

more...
No comment yet.
Scooped by Julien Hering, PhD
Scoop.it!

Deciphering a neuronal circuit that mediates appetite

Deciphering a neuronal circuit that mediates appetite | Neuroscience_topics | Scoop.it

Hypothalamic neurons that co-express agouti-related protein (AgRP), neuropeptide Y and γ-aminobutyric acid (GABA) are known to promote feeding and weight gain by integration of various nutritional, hormonal, and neuronal signals. Ablation of these neurons in mice leads to cessation of feeding that is accompanied by activation of Fos in most regions where they project. Previous experiments have indicated that the ensuing starvation is due to aberrant activation of the parabrachial nucleus (PBN) and it could be prevented by facilitating GABAA receptor signalling in the PBN within a critical adaptation period. We speculated that loss of GABA signalling from AgRP-expressing neurons (AgRP neurons) within the PBN results in unopposed excitation of the PBN, which in turn inhibits feeding. However, the source of the excitatory inputs to the PBN was unknown. Here we show that glutamatergic neurons in the nucleus tractus solitarius (NTS) and caudal serotonergic neurons control the excitability of PBN neurons and inhibit feeding. (...) Thus we identify the PBN as a hub that integrates signals from several brain regions to bidirectionally modulate feeding and body weight. - Nature 483, 594–597 (29 March 2012)

more...
Scooped by Julien Hering, PhD
Scoop.it!

A Network Diffusion Model of Disease Progression in Dementia

A Network Diffusion Model of Disease Progression in Dementia | Neuroscience_topics | Scoop.it

Patterns of dementia are known to fall into dissociated but dispersed brain networks, suggesting that the disease is transmitted along neuronal pathways rather than by proximity. This view is supported by neuropathological evidence for “prion-like” transsynaptic transmission of disease agents like misfolded tau and beta amyloid. We mathematically model this transmission by a diffusive mechanism mediated by the brain's connectivity network obtained from tractography of 14 healthy-brain MRIs. Subsequent graph theoretic analysis provides a fully quantitative, testable, predictive model of dementia. Specifically, we predict spatially distinct “persistent modes,” which, we found, recapitulate known patterns of dementia and match recent reports of selectively vulnerable dissociated brain networks. Model predictions also closely match T1-weighted MRI volumetrics of 18 Alzheimer's and 18 frontotemporal dementia subjects. Prevalence rates predicted by the model strongly agree with published data. This work has many important implications, including dimensionality reduction, differential diagnosis, and especially prediction of future atrophy using baseline MRI morphometrics. - Neuron 73(6), 2012

more...
No comment yet.
Scooped by Julien Hering, PhD
Scoop.it!

Gating Currents from Kv7 Channels Carrying Neuronal Hyperexcitability Mutations in the Voltage-Sensing Domain

Gating Currents from Kv7 Channels Carrying Neuronal Hyperexcitability Mutations in the Voltage-Sensing Domain | Neuroscience_topics | Scoop.it

hanges in voltage-dependent gating represent a common pathogenetic mechanism for genetically inherited channelopathies, such as benign familial neonatal seizures or peripheral nerve hyperexcitability caused by mutations in neuronal Kv7.2 channels. Mutation-induced changes in channel voltage dependence are most often inferred from macroscopic current measurements, a technique unable to provide a detailed assessment of the structural rearrangements underlying channel gating behavior; by contrast, gating currents directly measure voltage-sensor displacement during voltage-dependent gating. In this work, we describe macroscopic and gating current measurements, together with molecular modeling and molecular-dynamics simulations, from channels carrying mutations responsible for benign familial neonatal seizures and/or peripheral nerve hyperexcitability; Kv7.4 channels, highly related to Kv7.2 channels both functionally and structurally, were used for these experiments. The data obtained showed that mutations affecting charged residues located in the more distal portion of S4 decrease the stability of the open state and the active voltage-sensing domain configuration but do not directly participate in voltage sensing, whereas mutations affecting a residue (R4) located more proximally in S4 caused activation of gating-pore currents at depolarized potentials. These results reveal that distinct molecular mechanisms underlie the altered gating behavior of channels carrying disease-causing mutations at different voltage-sensing domain locations, thereby expanding our current view of the pathogenesis of neuronal hyperexcitability diseases. - Biophysical J 102(6), 2012

more...
No comment yet.
Scooped by Julien Hering, PhD
Scoop.it!

Insight Into a Shocking Therapy for Depression - ScienceNOW

Insight Into a Shocking Therapy for Depression - ScienceNOW | Neuroscience_topics | Scoop.it

Since the 1930s, doctors have been jolting the brains of depressed patients with electricity to relieve their symptoms. The treatment, known as electroconvulsive therapy (ECT), works, but it can cause memory loss and confusion and lead to difficulty forming new memories. Today, physicians generally limit it to patients who are severely ill, including those at risk for suicide. Now, a brain-imaging study highlights the part of the brain most affected, perhaps pointing to safer, less-invasive ways to achieve the same results. - ScienceNOW

more...
No comment yet.
Scooped by Julien Hering, PhD
Scoop.it!

Dissecting the age-related decline on spatial learning and memory tasks in rodent models: N-methyl-D-aspartate receptors and voltage-dependent Ca2+ channels in senescent synaptic plasticity

Dissecting the age-related decline on spatial learning and memory tasks in rodent models: N-methyl-D-aspartate receptors and voltage-dependent Ca2+ channels in senescent synaptic plasticity | Neuroscience_topics | Scoop.it

[Review] - Progress in Neurobiology 96(3), 2012

more...
No comment yet.
Scooped by Julien Hering, PhD
Scoop.it!

TRPM2 Contributes to Inflammatory and Neuropathic Pain through the Aggravation of Pronociceptive Inflammatory Responses in Mice

Accumulating evidence suggests that neuroimmune interactions contribute to pathological pain. Transient receptor potential melastatin 2 (TRPM2) is a nonselective Ca2+-permeable cation channel that acts as a sensor for reactive oxygen species. TRPM2 is expressed abundantly in immune cells and is important in inflammatory processes. (...) Together, these results suggest that TRPM2 expressed in macrophages and microglia aggravates peripheral and spinal pronociceptive inflammatory responses and contributes to the pathogenesis of inflammatory and neuropathic pain. - J Neurosc 32(11), 2012

more...
No comment yet.
Scooped by Julien Hering, PhD
Scoop.it!

Development of GABAergic inputs controls the contribution of maturing neurons to the adult hippocampal network

Development of GABAergic inputs controls the contribution of maturing neurons to the adult hippocampal network | Neuroscience_topics | Scoop.it

New neurons are continuously generated in the dentate gyrus (DG) in the adult hippocampus, and new granule cells (GCs) have been shown to be necessary for several aspects of learning and memory. Nonetheless, the limited information available regarding the anatomical and physiological development of synaptic inputs onto maturing neurons has restricted our understanding of how new GCs affect cognition. Here, we use photostimulation to demonstrate the time course by which anatomically isolated inhibitory inputs develop onto maturing GCs. We then show that the gradual development of inhibition is sufficient in a computational model to drive learning of novel information in young neurons. Finally, we validate this model observation by using slice physiology to show how inhibition regulates firing probability and plasticity in young GCs. Combined, these data demonstrate that the unique connectivity of immature GCs affords them a functional role that is different from mature neurons in the DG circuit, a distinction that potentially underlies many of the proposed functions of new neurons in the hippocampal network. PNAS 109(11), 2012

more...
No comment yet.
Scooped by Julien Hering, PhD
Scoop.it!

Gap Junctions Compensate for Sublinear Dendritic Integration in an Inhibitory Network

Electrically coupled inhibitory interneurons dynamically control network excitability. Yet little is known about how chemical and electrical synapses regulate their activity. Using two-photon glutamate uncaging and dendritic patch-clamp recordings, we found that the dendrites of cerebellar Golgi interneurons acted as passive cables. They conferred distance-dependent sublinear synaptic integration and weakened distal excitatory inputs. Gap junctions were present at a higher density on distal dendrites and contributed substantially to membrane conductance. Depolarization of one Golgi cell increased firing in its neighbors and inclusion of dendritic gap junctions in interneuron network models enabled distal excitatory synapses to drive network activity more effectively. Our results suggest that dendritic gap junctions counteract sublinear dendritic integration by enabling excitatory synaptic charge to spread into the dendrites of neighboring inhibitory interneurons. - Science 2012/03/08

more...
No comment yet.