Latest Articles Include:
- Synaptobrevin, Sphingolipids, and Secretion: Lube 'n' Go at the Synapse
Verhage M van Meer G - Neuron 62(5):603-605 (2009)
For neurotransmitter release to occur, proteins and lipids have to work together. The classical view of this process is that a variety of proteins work hard to force the unwilling, fusion-aversive lipids into merging. In this issue of Neuron, a study by Darios et al. paints the opposite picture: a lipid metabolite stimulates the reluctant vSNARE synaptobrevin to engage in fusogenic protein complexes. - Inhibitory Plasticity in Auditory Cortex
Nelken I - Neuron 62(5):605-607 (2009)
Arguably the most important property of neuronal circuits in general, and of cortical circuits in particular, is plasticity—the ability to change in response to past experience. While many studies of plasticity emphasize changes in excitatory transmission, in this issue of Neuron, Galindo-Leon et al. demonstrate the important role that increased inhibition may play in shaping cortical responses to behaviorally relevant stimuli. - Video Game for Monkeys
Schlag JD Schlag-Rey M - Neuron 62(5):608-609 (2009)
Recent progress in neurophysiological recording has developed in two directions. One relies on multimicroelectrodes to study correlations in neuron firing. The other relies on sophisticated tasks to distinguish successive stages of neuronal processing. In this issue of Neuron, Shichinohe et al. take this second approach to analyze neuronal mechanisms of pursuit. - Comparing the Bird in the Hand with the Ones in the Bush
Bunge SA Wendelken C - Neuron 62(5):609-611 (2009)
In this issue of Neuron, Boorman and colleagues shed new light on the roles of lateral frontopolar and ventromedial prefrontal cortices in task switching and decision making. - Neurons that Fire Together Also Conspire Together: Is Normal Sleep Circuitry Hijacked to Generate Epilepsy?
Beenhakker MP Huguenard JR - Neuron 62(5):612-632 (2009)
Brain circuits oscillate during sleep. The same circuits appear to generate pathological oscillations. In this review, we discuss recent advances in our understanding of how epilepsy co-opts normal, sleep-related circuits to generate seizures. - The Stoichiometry of AMPA Receptors and TARPs Varies by Neuronal Cell Type
Shi Y Lu W Milstein AD Nicoll RA - Neuron 62(5):633-640 (2009)
Synaptic AMPA receptors (AMPARs) are regulated by a family of auxiliary subunits known as transmembrane AMPA receptor regulatory proteins (TARPs). TARPs control the trafficking and gating of AMPARs. However, the number of TARP molecules that assemble within individual AMPAR channels is unknown. Here, we covalently link AMPARs to TARPs to investigate the properties of TARP/AMPAR complexes with known stoichiometry in HEK cells. We find that AMPARs are functional when associated with four, two, or no TARPs, and that the efficacy of the partial agonist kainate varies across these conditions, providing a sensitive assay for TARP/AMPAR stoichiometry. A comparison of these results with data obtained from hippocampal neurons demonstrates that native AMPARs associate with TARPs with a variable stoichiometry that depends on TARP expression level. Interestingly, AMPARs in hippocampal pyramidal neurons are saturated by TARP expression, while those in dentate gyrus granule neurons ! are not, indicating that variable TARP/AMPAR stoichiometry provides a mechanism for cell-type-specific regulation of AMPAR function. - Retinoid Signaling and Neurogenin2 Function Are Coupled for the Specification of Spinal Motor Neurons through a Chromatin Modifier CBP
Lee S Lee B Lee JW Lee SK - Neuron 62(5):641-654 (2009)
Extracellular signals and cell-intrinsic transcription factors cooperatively instruct generation of diverse neurons. However, little is known about how neural progenitors integrate both cues and orchestrate chromatin changes for neuronal specification. Here, we report that extrinsic signal retinoic acid (RA) and intrinsic transcription factor Neurogenin2 (Ngn2) collaboratively trigger transcriptionally active chromatin in spinal motor neuron genes during development. Retinoic acid receptor (RAR) binds Ngn2 and is thereby recruited to motor neuron genes targeted by Ngn2. RA then facilitates the recruitment of a histone acetyltransferase CBP to the Ngn2/RAR-complex, markedly inducing histone H3/H4-acetylation. Correspondingly, timely inactivation of CBP and its paralog p300 results in profound defects in motor neuron specification and motor axonal projection, accompanied by significantly reduced histone H3-acetylation of the motor neuron enhancer. Our study uncovers the ! mechanism by which extrinsic RA-signal and intrinsic transcription factor Ngn2 cooperate for cell fate specification through their synergistic activity to trigger transcriptionally active chromatin. - Neural Activity Regulates Synaptic Properties and Dendritic Structure In Vivo through Calcineurin/NFAT Signaling
Schwartz N Schohl A Ruthazer ES - Neuron 62(5):655-669 (2009)
The calcium-regulated protein phosphatase Calcineurin (CaN) participates in synaptic plasticity and the regulation of transcription factors, including Nuclear Factor of Activated T cells (NFAT). To understand how CaN contributes to neuronal circuit development, whole-cell mEPSC recordings and multiphoton imaging were performed in the visual system of living Xenopus laevis tadpoles electroporated to express either a CaN phosphatase inhibitor or N-VIVIT, a nuclear localization sequence-tagged VIVIT peptide that blocks the binding of CaN to select substrates including NFAT. Both strategies increased mEPSC frequency and dendritic arbor complexity in tectal neurons over 3 days. Expression of either of two constitutively active Xenopus NFATs (CA-NFATs) restored normal synaptic properties in neurons expressing N-VIVIT. However, the morphological phenotype was only rescued by a CA-NFAT bearing an intact regulatory domain, implying that transcriptional control of morphological ! and electrophysiological properties of neurons is mediated by distinct NFAT interactions. - Activity-Dependent Tuning of Inhibitory Neurotransmission Based on GABAAR Diffusion Dynamics
Bannai H Lévi S Schweizer C Inoue T Launey T Racine V Sibarita JB Mikoshiba K Triller A - Neuron 62(5):670-682 (2009)
An activity-dependent change in synaptic efficacy is a central tenet in learning, memory, and pathological states of neuronal excitability. The lateral diffusion dynamics of neurotransmitter receptors are one of the important parameters regulating synaptic efficacy. We report here that neuronal activity modifies diffusion properties of type-A GABA receptors (GABAAR) in cultured hippocampal neurons: enhanced excitatory synaptic activity decreases the cluster size of GABAARs and reduces GABAergic mIPSC. Single-particle tracking of the GABAAR γ2 subunit labeled with quantum dots reveals that the diffusion coefficient and the synaptic confinement domain size of GABAAR increases in parallel with neuronal activity, depending on Ca2+ influx and calcineurin activity. These results indicate that GABAAR diffusion dynamics are directly linked to rapid and plastic modifications of inhibitory synaptic transmission in response to changes in intracellular Ca2+ concentration. This tr! ansient activity-dependent reduction of inhibition would favor the onset of LTP during conditioning. - Sphingosine Facilitates SNARE Complex Assembly and Activates Synaptic Vesicle Exocytosis
Darios F Wasser C Shakirzyanova A Giniatullin A Goodman K Munoz-Bravo JL Raingo J Jorgacevski J Kreft M Zorec R Rosa JM Gandia L Gutiérrez LM Binz T Giniatullin R Kavalali ET Davletov B - Neuron 62(5):683-694 (2009)
Synaptic vesicles loaded with neurotransmitters fuse with the plasma membrane to release their content into the extracellular space, thereby allowing neuronal communication. The membrane fusion process is mediated by a conserved set of SNARE proteins: vesicular synaptobrevin and plasma membrane syntaxin and SNAP-25. Recent data suggest that the fusion process may be subject to regulation by local lipid metabolism. Here, we have performed a screen of lipid compounds to identify positive regulators of vesicular synaptobrevin. We show that sphingosine, a releasable backbone of sphingolipids, activates synaptobrevin in synaptic vesicles to form the SNARE complex implicated in membrane fusion. Consistent with the role of synaptobrevin in vesicle fusion, sphingosine upregulated exocytosis in isolated nerve terminals, neuromuscular junctions, neuroendocrine cells and hippocampal neurons, but not in neurons obtained from synaptobrevin-2 knockout mice. Further mechanistic insig! hts suggest that sphingosine acts on the synaptobrevin/phospholipid interface, defining a novel function for this important lipid regulator. - Synchronization of Midbrain Dopaminergic Neurons Is Enhanced by Rewarding Events
Joshua M Adler A Prut Y Vaadia E Wickens JR Bergman H - Neuron 62(5):695-704 (2009)
The basal ganglia network is divided into two functionally related subsystems: the neuromodulators and the main axis. It is assumed that neuromodulators adjust cortico-striatal coupling. This adjustment might depend on the response properties and temporal interactions between neuromodulators. We studied functional interactions between simultaneously recorded pairs of neurons in the basal ganglia while monkeys performed a classical conditioning task that included rewarding, neutral, and aversive events. Neurons that belong to a single neuromodulator group exhibited similar average responses, whereas main axis neurons responded in a highly diverse manner. Dopaminergic neuromodulators transiently increased trial-to-trial (noise) correlation following rewarding but not aversive events, whereas cholinergic neurons of the striatum decreased their trial-to-trial correlation. These changes in functional connectivity occurred at different epochs of the trial. Thus, the coding s! cheme of neuromodulators (but not main axis neurons) can be viewed as a single-dimensional code that is further enriched by dynamic neuronal interactions. - Inhibitory Plasticity in a Lateral Band Improves Cortical Detection of Natural Vocalizations
Galindo-Leon EE Lin FG Liu RC - Neuron 62(5):705-716 (2009)
The interplay between excitation and inhibition in the auditory cortex is crucial for the processing of acoustic stimuli. However, the precise role that inhibition plays in the distributed cortical encoding of natural vocalizations has not been well studied. We recorded single units (SUs) and local field potentials (LFPs) in the awake mouse auditory cortex while presenting pup isolation calls to animals that either do (mothers) or do not (virgins) recognize the sounds as behaviorally relevant. In both groups, we observed substantial call-evoked inhibition. However, in mothers this was earlier, longer, stronger, and more stereotyped compared to virgins. This difference was most apparent for recording sites tuned to tone frequencies lower than the pup calls' high-ultrasonic frequency range. We hypothesize that this auditory cortical inhibitory plasticity improves pup call detection in a relatively specific manner by increasing the contrast between call-evoked responses a! rising from high-ultrasonic and lateral frequency neural populations. - Memory and Decision Making in the Frontal Cortex during Visual Motion Processing for Smooth Pursuit Eye Movements
Shichinohe N Akao T Kurkin S Fukushima J Kaneko CR Fukushima K - Neuron 62(5):717-732 (2009)
Cortical motor areas are thought to contribute "higher-order processing," but what that processing might include is unknown. Previous studies of the smooth pursuit-related discharge of supplementary eye field (SEF) neurons have not distinguished activity associated with the preparation for pursuit from discharge related to processing or memory of the target motion signals. Using a memory-based task designed to separate these components, we show that the SEF contains signals coding retinal image-slip-velocity, memory, and assessment of visual motion direction, the decision of whether to pursue, and the preparation for pursuit eye movements. Bilateral muscimol injection into SEF resulted in directional errors in smooth pursuit, errors of whether to pursue, and impairment of initial correct eye movements. These results suggest an important role for the SEF in memory and assessment of visual motion direction and the programming of appropriate pursuit eye movements. - How Green Is the Grass on the Other Side? Frontopolar Cortex and the Evidence in Favor of Alternative Courses of Action
Boorman ED Behrens TE Woolrich MW Rushworth MF - Neuron 62(5):733-743 (2009)
Behavioral flexibility is the hallmark of goal-directed behavior. Whereas a great deal is known about the neural substrates of behavioral adjustment when it is explicitly cued by features of the external environment, little is known about how we adapt our behavior when such changes are made on the basis of uncertain evidence. Using a Bayesian reinforcement-learning model and fMRI, we show that frontopolar cortex (FPC) tracks the relative advantage in favor of switching to a foregone alternative when choices are made voluntarily. Changes in FPC functional connectivity occur when subjects finally decide to switch to the alternative behavior. Moreover, interindividual variation in the FPC signal predicts interindividual differences in effectively adapting behavior. By contrast, ventromedial prefrontal cortex (vmPFC) encodes the relative value of the current decision. Collectively, these findings reveal complementary prefrontal computations essential for promoting short- a! nd long-term behavioral flexibility.
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