Hot off the presses! Apr 14 Neuron

The Apr 14 issue of the Neuron is now up on Pubget (About Neuron): if you're at a subscribing institution, just click the link in the latest link at the home page. (Note you'll only be able to get all the PDFs in the issue if your institution subscribes to Pubget.)

Latest Articles Include:

• Convergence in the Piriform Cortex
  - Neuron (Cambridge Mass ) 70(1):1-2 (2011)
  How are the responses to distinct chemical features integrated to form an olfactory perceptual object? In this issue of Neuron, Davison and Ehlers show that individual piriform cortex neurons receive convergent input from up to 10% of main olfactory bulb glomeruli and are activated by specific spatial patterns of coactive glomeruli.
• An Inside Look at Hippocampal Silent Cells
  - Neuron (Cambridge Mass ) 70(1):3-5 (2011)
  Hippocampal pyramidal cells can be divided into place cells, which fire action potentials when an animal is in specific locations, and silent cells, which are not spatially selective. In this issue of Neuron, Epsztein et al. find intracellular differences between place and silent cells by using whole-cell recordings in freely moving rats.
• Allocating Attention in Rank-Ordered Groups
  - Neuron (Cambridge Mass ) 70(1):5-7 (2011)
  When confronted with multiple stimuli, it is often necessary to prioritize one's attentional resources. In this issue, Lennert and Martinez-Trujillo (2011) investigate the neural dynamics in dorsolateral prefrontal cortex for stimulus pairs of differing importance and demonstrate that the responses to the lesser stimuli become increasingly suppressed with increasing difference.
• Traces of Drosophila Memory
  - Neuron (Cambridge Mass ) 70(1):8-19 (2011)
  Studies using functional cellular imaging of living flies have identified six memory traces that form in the olfactory nervous system after conditioning with odors. These traces occur in distinct nodes of the olfactory nervous system, form and disappear across different windows of time, and are detected in the imaged neurons as increased calcium influx or synaptic release in response to the conditioned odor. Three traces form at or near acquisition and coexist with short-term behavioral memory. One trace forms with a delay after learning and coexists with intermediate-term behavioral memory. Two traces form many hours after acquisition and coexist with long-term behavioral memory. The transient memory traces may support behavior across the time windows of their existence. The experimental approaches for dissecting memory formation in the fly, ranging from the molecular to the systems, make it an ideal system for elucidating the logic by which the nervous system organiz! es and stores different temporal forms of memory.
• Neural Systems Governed by Nicotinic Acetylcholine Receptors: Emerging Hypotheses
  - Neuron (Cambridge Mass ) 70(1):20-33 (2011)
  Cholinergic neurons and nicotinic acetylcholine receptors (nAChRs) in the brain participate in diverse functions: reward, learning and memory, mood, sensory processing, pain, and neuroprotection. Nicotinic systems also have well-known roles in drug abuse. Here, we review recent insights into nicotinic function, linking exogenous and endogenous manipulations of nAChRs to alterations in synapses, circuits, and behavior. We also discuss how these contemporary advances can motivate attempts to exploit nicotinic systems therapeutically in Parkinson's disease, cognitive decline, epilepsy, and schizophrenia.
• Experience-Dependent Retinogeniculate Synapse Remodeling Is Abnormal in MeCP2-Deficient Mice
  - Neuron (Cambridge Mass ) 70(1):35-42 (2011)
  Mutations in MECP2 underlie the neurodevelopmental disorder Rett syndrome (RTT). One hallmark of RTT is relatively normal development followed by a later onset of symptoms. Growing evidence suggests an etiology of disrupted synaptic function, yet it is unclear how these abnormalities explain the clinical presentation of RTT. Here we investigate synapse maturation in Mecp2-deficient mice at a circuit with distinct developmental phases: the retinogeniculate synapse. We find that synapse development in mutants is comparable to that of wild-type littermates between postnatal days 9 and 21, indicating that initial phases of synapse formation, elimination, and strengthening are not significantly affected by MeCP2 absence. However, during the subsequent experience-dependent phase of synapse remodeling, the circuit becomes abnormal in mutants as retinal innervation of relay neurons increases and retinal inputs fail to strengthen further. Moreover, synaptic plasticity in respon! se to visual deprivation is disrupted in mutants. These results suggest a crucial role for Mecp2 in experience-dependent refinement of synaptic circuits.
• Reevaluating the Role of LTD in Cerebellar Motor Learning
  - Neuron (Cambridge Mass ) 70(1):43-50 (2011)
  Long-term depression at parallel fiber-Purkinje cell synapses (PF-PC LTD) has been proposed to be required for cerebellar motor learning. To date, tests of this hypothesis have sought to interfere with receptors (mGluR1) and enzymes (PKC, PKG, or αCamKII) necessary for induction of PF-PC LTD and thereby determine if cerebellar motor learning is impaired. Here, we tested three mutant mice that target the expression of PF-PC LTD by blocking internalization of AMPA receptors. Using three different cerebellar coordination tasks (adaptation of the vestibulo-ocular reflex, eyeblink conditioning, and locomotion learning on the Erasmus Ladder), we show that there is no motor learning impairment in these mutant mice that lack PF-PC LTD. These findings demonstrate that PF-PC LTD is not essential for cerebellar motor learning.
• A RasGRP, C. elegans RGEF-1b, Couples External Stimuli to Behavior by Activating LET-60 (Ras) in Sensory Neurons
  - Neuron (Cambridge Mass ) 70(1):51-65 (2011)
  RasGRPs, which load GTP onto Ras and Rap1, are expressed in vertebrate and invertebrate neurons. The functions, regulation, and mechanisms of action of neuronal RasGRPs are unknown. Here, we show how C. elegans RGEF-1b, a prototypical neuronal RasGRP, regulates a critical behavior. Chemotaxis to volatile odorants was disrupted in RGEF-1b-deficient (rgef-1−/−) animals and wild-type animals expressing dominant-negative RGEF-1b in AWC sensory neurons. AWC-specific expression of RGEF-1b-GFP restored chemotaxis in rgef-1−/− mutants. Signals disseminated by RGEF-1b in AWC neurons activated a LET-60 (Ras)-MPK-1 (ERK) signaling cascade. Other RGEF-1b and LET-60 effectors were dispensable for chemotaxis. A bifunctional C1 domain controlled intracellular targeting and catalytic activity of RGEF-1b and was essential for sensory signaling in vivo. Chemotaxis was unaffected when Ca2+-binding EF hands and a conserved phosphorylation site of RGEF-1b were inactivated. Diacylgl! ycerol-activated RGEF-1b links external stimuli (odorants) to behavior (chemotaxis) by activating the LET-60-MPK-1 pathway in specific neurons.
• Muskelin Regulates Actin Filament- and Microtubule-Based GABAA Receptor Transport in Neurons
  - Neuron (Cambridge Mass ) 70(1):66-81 (2011)
  Intracellular transport regulates protein turnover including endocytosis. Because of the spatial segregation of F-actin and microtubules, internalized cargo vesicles need to employ myosin and dynein motors to traverse both cytoskeletal compartments. Factors specifying cargo delivery across both tracks remain unknown. We identified muskelin to interconnect retrograde F-actin- and microtubule-dependent GABAA receptor (GABAAR) trafficking. GABAARs regulate synaptic transmission, plasticity, and network oscillations. GABAAR α1 and muskelin interact directly, undergo neuronal cotransport, and associate with myosin VI or dynein motor complexes in subsequent steps of GABAAR endocytosis. Inhibition of either transport route selectively interferes with receptor internalization or degradation. Newly generated muskelin KO mice display depletion of both transport steps and a high-frequency ripple oscillation phenotype. A diluted coat color of muskelin KOs further suggests muskeli! n transport functions beyond neurons. Our data suggest the concept that specific trafficking factors help cargoes to traverse both F-actin and microtubule compartments, thereby regulating their fate.
• Neural Circuit Mechanisms for Pattern Detection and Feature Combination in Olfactory Cortex
  - Neuron (Cambridge Mass ) 70(1):82-94 (2011)
  Odors are initially encoded in the brain as a set of distinct physicochemical characteristics but are ultimately perceived as a unified sensory object—a "smell." It remains unclear how chemical features encoded by diverse odorant receptors and segregated glomeruli in the main olfactory bulb (MOB) are assembled into integrated cortical representations. Combining patterned optical microstimulation of MOB with in vivo electrophysiological recordings in anterior piriform cortex (PCx), we assessed how cortical neurons decode complex activity patterns distributed across MOB glomeruli. PCx firing was insensitive to single-glomerulus photostimulation. Instead, individual cells reported higher-order combinations of coactive glomeruli resembling odor-evoked sensory maps. Intracellular recordings revealed a corresponding circuit architecture providing each cortical neuron with weak synaptic input from a distinct subpopulation of MOB glomeruli. PCx neurons thus detect specif! ic glomerular ensembles, providing an explicit neural representation of chemical feature combinations that are the hallmark of complex odor stimuli.
• CaV2.3 Channels Are Critical for Oscillatory Burst Discharges in the Reticular Thalamus and Absence Epilepsy
  - Neuron (Cambridge Mass ) 70(1):95-108 (2011)
  Neurons of the reticular thalamus (RT) display oscillatory burst discharges that are believed to be critical for thalamocortical network oscillations related to absence epilepsy. Ca2+-dependent mechanisms underlie such oscillatory discharges. However, involvement of high-voltage activated (HVA) Ca2+ channels in this process has been discounted. We examined this issue closely using mice deficient for the HVA CaV2.3 channels. In brain slices of CaV2.3−/−, a hyperpolarizing current injection initiated a low-threshold burst of spikes in RT neurons; however, subsequent oscillatory burst discharges were severely suppressed, with a significantly reduced slow afterhyperpolarization (AHP). Consequently, the lack of CaV2.3 resulted in a marked decrease in the sensitivity of the animal to γ-butyrolactone-induced absence epilepsy. Local blockade of CaV2.3 channels in the RT mimicked the results of CaV2.3−/− mice. These results provide strong evidence that CaV2.3 channels ! are critical for oscillatory burst discharges in RT neurons and for the expression of absence epilepsy.
• Intracellular Determinants of Hippocampal CA1 Place and Silent Cell Activity in a Novel Environment
  - Neuron (Cambridge Mass ) 70(1):109-120 (2011)
  For each environment a rodent has explored, its hippocampus contains a map consisting of a unique subset of neurons, called place cells, that have spatially tuned spiking there, with the remaining neurons being essentially silent. Using whole-cell recording in freely moving rats exploring a novel maze, we observed differences in intrinsic cellular properties and input-based subthreshold membrane potential levels underlying this division into place and silent cells. Compared to silent cells, place cells had lower spike thresholds and peaked versus flat subthreshold membrane potentials as a function of animal location. Both differences were evident from the beginning of exploration. Additionally, future place cells exhibited higher burst propensity before exploration. Thus, internal settings appear to predetermine which cells will represent the next novel environment encountered. Furthermore, place cells fired spatially tuned bursts with large, putatively calcium-mediate! d depolarizations that could trigger plasticity and stabilize the new map for long-term storage. Our results provide new insight into hippocampal memory formation.
• Cortical Map Plasticity Improves Learning but Is Not Necessary for Improved Performance
  - Neuron (Cambridge Mass ) 70(1):121-131 (2011)
  Cortical map plasticity is believed to be a key substrate of perceptual and skill learning. In the current study, we quantified changes in perceptual ability after pairing tones with stimulation of the cholinergic nucleus basalis to induce auditory cortex map plasticity outside of a behavioral context. Our results provide evidence that cortical map plasticity can enhance perceptual learning. However, auditory cortex map plasticity fades over weeks even though tone discrimination performance remains stable. This observation is consistent with recent reports that cortical map expansions associated with perceptual and motor learning are followed by a period of map renormalization without a decrement in performance. Our results indicate that cortical map plasticity enhances perceptual learning, but is not necessary to maintain improved discriminative ability.
• Intact Performance on Feature-Ambiguous Discriminations in Rats with Lesions of the Perirhinal Cortex
  - Neuron (Cambridge Mass ) 70(1):132-140 (2011)
  We developed a behavioral paradigm for the rat that made it possible to separate the evaluation of memory functions from the evaluation of perceptual functions. Animals were given extensive training on an automated two-choice discrimination task and then maintained their memory performance at a high level while interpolated probe trials tested visual perceptual ability. The probe trials systematically varied the degree of feature ambiguity between the stimuli, such that perceptual functions could be tested across 14 different levels of difficulty. As feature ambiguity increased, performance declined in an orderly, monotonic manner (from 87% correct to chance, 50% correct). Bilateral lesions of the perirhinal cortex fully spared the capacity to make feature-ambiguous discriminations and the performance of lesioned and intact animals was indistinguishable at every difficulty level. In contrast, the perirhinal lesions did impair recognition memory. The findings suggest th! at the perirhinal cortex is important for memory and not for perceptual functions.
• Strength of Response Suppression to Distracter Stimuli Determines Attentional-Filtering Performance in Primate Prefrontal Neurons
  - Neuron (Cambridge Mass ) 70(1):141-152 (2011)
  Neurons in the primate dorsolateral prefrontal cortex (dlPFC) filter attend targets distinctly from distracters through their response rates. The extent to which this ability correlates with the organism's performance, and the neural processes underlying it, remain unclear. We trained monkeys to attend to a visual target that differed in rank along a color-ordinal scale from that of a distracter. The animals' performance at focusing attention on the target and filtering out the distracter improved as ordinal distance between the stimuli increased. Importantly, dlPFC neurons also improved their filtering performance with increasing ordinal target-distracter distance; they built up their response rate in anticipation of the target-distracter onset, and then units encoding target representations increased their firing rate by similar amounts, whereas units encoding distracter representations gradually suppressed their rates as the interstimulus ordinal distance increased.! These results suggest that attentional-filtering performance in primates relies upon dlPFC neurons' ability to suppress distracter representations.
• Regional Slow Waves and Spindles in Human Sleep
  - Neuron (Cambridge Mass ) 70(1):153-169 (2011)
  The most prominent EEG events in sleep are slow waves, reflecting a slow (<1 Hz) oscillation between up and down states in cortical neurons. It is unknown whether slow oscillations are synchronous across the majority or the minority of brain regions—are they a global or local phenomenon? To examine this, we recorded simultaneously scalp EEG, intracerebral EEG, and unit firing in multiple brain regions of neurosurgical patients. We find that most sleep slow waves and the underlying active and inactive neuronal states occur locally. Thus, especially in late sleep, some regions can be active while others are silent. We also find that slow waves can propagate, usually from medial prefrontal cortex to the medial temporal lobe and hippocampus. Sleep spindles, the other hallmark of NREM sleep EEG, are likewise predominantly local. Thus, intracerebral communication during sleep is constrained because slow and spindle oscillations often occur out-of-phase in different brain r! egions. Video Abstract To view the video inline, enable JavaScript on your browser. However, you can download and view the video by clicking on the icon below Download this Video (15194 K)
• Synaptic Mechanisms Underlying Sparse Coding of Active Touch
  - Neuron (Cambridge Mass ) 70(1):170 (2011)