Hot off the presses! Sep 08 Neuron

The Sep 08 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:

• DEG/ENaCs Lead by a Nose: Mechanotransduction in a Polymodal Sensory Neuron
  - Neuron 71(5):763-765 (2011)
  Degenerin/epithelial sodium channels (DEG/ENaCs) are luminaries of gentle touch in Caenorhabditis elegans. In this issue of Neuron, Geffeney et al. demonstrate that eponymous DEG-1 channels carry mechanotransduction currents in a polymodal neuron, where they act upstream of transient receptor potential (TRP) channels.
• Reorganization of Striatal Inhibitory Microcircuits Leads to Pathological Synchrony in the Basal Ganglia
  - Neuron 71(5):766-768 (2011)
  Neural synchronization plays an important role in information flow in the nervous system under healthy and pathological conditions. In this issue of Neuron, Gittis et al. show that reorganization of striatal microcircuits promotes synchronous activity and may underlie the pathological network oscillations at the root of motor symptoms described in Parkinson's disease.
• Life and Death Decision in Adult Neurogenesis: In Praise of Napping
  - Neuron 71(5):768-771 (2011)
  Among the thousands of new neurons that integrate into the adult olfactory bulb each day, 50% are eliminated through apoptosis. In this issue of Neuron, Yokoyama et al. take steps toward deciphering the behavioral contexts that regulate newborn cell elimination.
• Dendritic Spines and Distributed Circuits
  - Neuron 71(5):772-781 (2011)
  Dendritic spines receive most excitatory connections in pyramidal cells and many other principal neurons. But why do neurons use spines, when they could accommodate excitatory contacts directly on their dendritic shafts? One suggestion is that spines serve to connect with passing axons, thus increasing the connectivity of the dendrites. Another hypothesis is that spines are biochemical compartments that enable input-specific synaptic plasticity. A third possibility is that spines have an electrical role, filtering synaptic potentials and electrically isolating inputs from each other. In this review, I argue that, when viewed from the perspective of the circuit function, these three functions dovetail with one another to achieve a single overarching goal: to implement a distributed circuit with widespread connectivity. Spines would endow these circuits with nonsaturating, linear integration and input-specific learning rules, which would enable them to function as neural networks, with emergent encoding and processing of information.
• Role of Astrocytes in Neurovascular Coupling
  - Neuron 71(5):782-797 (2011)
  Neural activity is intimately tied to blood flow in the brain. This coupling is specific enough in space and time that modern imaging methods use local hemodynamics as a measure of brain activity. In this review, we discuss recent evidence indicating that neuronal activity is coupled to local blood flow changes through an intermediary, the astrocyte. We highlight unresolved issues regarding the role of astrocytes and propose ways to address them using novel techniques. Our focus is on cellular level analysis in vivo, but we also relate mechanistic insights gained from ex vivo experiments to native tissue. We also review some strategies to harness advances in optical and genetic methods to study neurovascular coupling in the intact brain.
• Rapid Plasticity of Visual Responses in the Adult Lateral Geniculate Nucleus
  - Neuron 71(5):812-819 (2011)
  Compared to the developing visual system, where neuronal plasticity has been well characterized at multiple levels, little is known about plasticity in the adult, particularly within subcortical structures. We made intraocular injections of 2-amino-4-phosphonobutyric acid (APB) in adult cats to block visual responses in On-center retinal ganglion cells and examined the consequences on visual responses in the lateral geniculate nucleus (LGN) of the thalamus. In contrast to current views of retinogeniculate organization, which hold that On-center LGN neurons should become silent with APB, we find that 50% of On-center neurons rapidly develop Off-center responses. The time course of these emergent responses and the actions of APB in the retina indicate the plasticity occurs within the LGN. These results suggest there is greater divergence of retinogeniculate connections than previously recognized and that functionally silent, nonspecific retinal inputs can serve as a subs! trate for rapid plasticity in the adult.
• Control of Neuronal Morphology by the Atypical Cadherin Fat3
  - Neuron 71(5):820-832 (2011)
  Neurons receive signals through dendrites that vary widely in number and organization, ranging from one primary dendrite to multiple complex dendritic trees. For example, retinal amacrine cells (ACs) project primary dendrites into a discrete synaptic layer called the inner plexiform layer (IPL) and only rarely extend processes into other retinal layers. Here, we show that the atypical cadherin Fat3 ensures that ACs develop this unipolar morphology. AC precursors are initially multipolar but lose neurites as they migrate through the neuroblastic layer. In fat3 mutants, pruning is unreliable and ACs elaborate two dendritic trees: one in the IPL and a second projecting away from the IPL that stratifies to form an additional synaptic layer. Since complex nervous systems are characterized by the addition of layers, these results demonstrate that mutations in a single gene can cause fundamental changes in circuit organization that may drive nervous system evolution. 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 (42472 K)
• Nitration of Tyrosine 10 Critically Enhances Amyloid β Aggregation and Plaque Formation
  - Neuron 71(5):833-844 (2011)
  Part of the inflammatory response in Alzheimer's disease (AD) is the upregulation of the inducible nitric oxide synthase (NOS2) resulting in increased NO production. NO contributes to cell signaling by inducing posttranslational protein modifications. Under pathological conditions there is a shift from the signal transducing actions to the formation of protein tyrosine nitration by secondary products like peroxynitrite and nitrogen dioxide. We identified amyloid β (Aβ) as an NO target, which is nitrated at tyrosine 10 (3NTyr10-Aβ). Nitration of Aβ accelerated its aggregation and was detected in the core of Aβ plaques of APP/PS1 mice and AD brains. NOS2 deficiency or oral treatment with the NOS2 inhibitor L-NIL strongly decreased 3NTyr10-Aβ, overall Aβ deposition and cognitive dysfunction in APP/PS1 mice. Further, injection of 3NTyr10-Aβ into the brain of young APP/PS1 mice induced β-amyloidosis. This suggests a disease modifying role for NOS2 in AD and therefo! re represents a potential therapeutic target.
• DEG/ENaC but Not TRP Channels Are the Major Mechanoelectrical Transduction Channels in a C. elegans Nociceptor
  - Neuron 71(5):845-857 (2011)
  Many nociceptors detect mechanical cues, but the ion channels responsible for mechanotransduction in these sensory neurons remain obscure. Using in vivo recordings and genetic dissection, we identified the DEG/ENaC protein, DEG-1, as the major mechanotransduction channel in ASH, a polymodal nociceptor in Caenorhabditis elegans. But DEG-1 is not the only mechanotransduction channel in ASH: loss of deg-1 revealed a minor current whose properties differ from those expected of DEG/ENaC channels. This current was independent of two TRPV channels expressed in ASH. Although loss of these TRPV channels inhibits behavioral responses to noxious stimuli, we found that both mechanoreceptor currents and potentials were essentially wild-type in TRPV mutants. We propose that ASH nociceptors rely on two genetically distinct mechanotransduction channels and that TRPV channels contribute to encoding and transmitting information. Because mammalian and insect nociceptors also coexpress DE! G/ENaCs and TRPVs, the cellular functions elaborated here for these ion channels may be conserved.
• Rapid Target-Specific Remodeling of Fast-Spiking Inhibitory Circuits after Loss of Dopamine
  - Neuron 71(5):858-868 (2011)
  In Parkinson's disease (PD), dopamine depletion alters neuronal activity in the direct and indirect pathways and leads to increased synchrony in the basal ganglia network. However, the origins of these changes remain elusive. Because GABAergic interneurons regulate activity of projection neurons and promote neuronal synchrony, we recorded from pairs of striatal fast-spiking (FS) interneurons and direct- or indirect-pathway MSNs after dopamine depletion with 6-OHDA. Synaptic properties of FS-MSN connections remained similar, yet within 3 days of dopamine depletion, individual FS cells doubled their connectivity to indirect-pathway MSNs, whereas connections to direct-pathway MSNs remained unchanged. A model of the striatal microcircuit revealed that such increases in FS innervation were effective at enhancing synchrony within targeted cell populations. These data suggest that after dopamine depletion, rapid target-specific microcircuit organization in the striatum may le! ad to increased synchrony of indirect-pathway MSNs that contributes to pathological network oscillations and motor symptoms of PD.
• Loss of Sensory Input Causes Rapid Structural Changes of Inhibitory Neurons in Adult Mouse Visual Cortex
  - Neuron 71(5):869-882 (2011)
  A fundamental property of neuronal circuits is the ability to adapt to altered sensory inputs. It is well established that the functional synaptic changes underlying this adaptation are reflected by structural modifications in excitatory neurons. In contrast, the degree to which structural plasticity in inhibitory neurons accompanies functional changes is less clear. Here, we use two-photon imaging to monitor the fine structure of inhibitory neurons in mouse visual cortex after deprivation induced by retinal lesions. We find that a subset of inhibitory neurons carry dendritic spines, which form glutamatergic synapses. Removal of visual input correlates with a rapid and lasting reduction in the number of inhibitory cell spines. Similar to the effects seen for dendritic spines, the number of inhibitory neuron boutons dropped sharply after retinal lesions. Together, these data suggest that structural changes in inhibitory neurons may precede structural changes in excitato! ry circuitry, which ultimately result in functional adaptation following sensory deprivation.
• Elimination of Adult-Born Neurons in the Olfactory Bulb Is Promoted during the Postprandial Period
  - Neuron 71(5):883-897 (2011)
  Granule cells (GCs) in the mouse olfactory bulb (OB) continue to be generated in adulthood, with nearly half incorporated and the remainder eliminated. Here, we show that elimination of adult-born GCs is promoted during a short time window in the postprandial period. Under restricted feeding, the number of apoptotic GCs specifically increased within a few hours after the start of feeding. This enhanced GC apoptosis occurred in association with postprandial behaviors that included grooming, resting, and sleeping, and was particularly correlated with the length of postprandial sleep. Further, deprivation of olfactory sensory experience in the local OB area potentiated the extent of GC elimination in that area during the postprandial period. Sensory experience-dependent enhancement of GC elimination also occurred during postprandial period under natural feeding condition. These results suggest that extensive structural reorganization of bulbar circuitry occurs during the ! postprandial period, reflecting sensory experience during preceding waking period.
• Single Units in the Medial Prefrontal Cortex with Anxiety-Related Firing Patterns Are Preferentially Influenced by Ventral Hippocampal Activity
  - Neuron 71(5):898-910 (2011)
  The medial prefrontal cortex (mPFC) and ventral hippocampus (vHPC) functionally interact during innate anxiety tasks. To explore the consequences of this interaction, we examined task-related firing of single units from the mPFC of mice exploring standard and modified versions of the elevated plus maze (EPM), an innate anxiety paradigm. Hippocampal local field potentials (LFPs) were simultaneously monitored. The population of mPFC units distinguished between safe and aversive locations within the maze, regardless of the nature of the anxiogenic stimulus. Strikingly, mPFC units with stronger task-related activity were more strongly coupled to theta-frequency activity in the vHPC LFP. Lastly, task-related activity was inversely correlated with behavioral measures of anxiety. These results clarify the role of the vHPC-mPFC circuit in innate anxiety and underscore how specific inputs may be involved in the generation of behaviorally relevant neural activity within the mPFC.
• The Sound of Silence: Ionic Mechanisms Encoding Sound Termination
  - Neuron 71(5):911-925 (2011)
  Offset responses upon termination of a stimulus are crucial for perceptual grouping and gap detection. These gaps are key features of vocal communication, but an ionic mechanism capable of generating fast offsets from auditory stimuli has proven elusive. Offset firing arises in the brainstem superior paraolivary nucleus (SPN), which receives powerful inhibition during sound and converts this into precise action potential (AP) firing upon sound termination. Whole-cell patch recording in vitro showed that offset firing was triggered by IPSPs rather than EPSPs. We show that AP firing can emerge from inhibition through integration of large IPSPs, driven by an extremely negative chloride reversal potential (ECl), combined with a large hyperpolarization-activated nonspecific cationic current (IH), with a secondary contribution from a T-type calcium conductance (ITCa). On activation by the IPSP, IH potently accelerates the membrane time constant, so when the sound ceases, a r! apid repolarization triggers multiple offset APs that match onset timing accuracy.
• Sound Texture Perception via Statistics of the Auditory Periphery: Evidence from Sound Synthesis
  - Neuron 71(5):926-940 (2011)
  Rainstorms, insect swarms, and galloping horses produce "sound textures"—the collective result of many similar acoustic events. Sound textures are distinguished by temporal homogeneity, suggesting they could be recognized with time-averaged statistics. To test this hypothesis, we processed real-world textures with an auditory model containing filters tuned for sound frequencies and their modulations, and measured statistics of the resulting decomposition. We then assessed the realism and recognizability of novel sounds synthesized to have matching statistics. Statistics of individual frequency channels, capturing spectral power and sparsity, generally failed to produce compelling synthetic textures; however, combining them with correlations between channels produced identifiable and natural-sounding textures. Synthesis quality declined if statistics were computed from biologically implausible auditory models. The results suggest that sound texture perception is m! ediated by relatively simple statistics of early auditory representations, presumably computed by downstream neural populations. The synthesis methodology offers a powerful tool for their further investigation.
• Visual Feature-Tolerance in the Reading Network
  - Neuron 71(5):941-953 (2011)
  A century of neurology and neuroscience shows that seeing words depends on ventral occipital-temporal (VOT) circuitry. Typically, reading is learned using high-contrast line-contour words. We explored whether a specific VOT region, the visual word form area (VWFA), learns to see only these words or recognizes words independent of the specific shape-defining visual features. Word forms were created using atypical features (motion-dots, luminance-dots) whose statistical properties control word-visibility. We measured fMRI responses as word form visibility varied, and we used TMS to interfere with neural processing in specific cortical circuits, while subjects performed a lexical decision task. For all features, VWFA responses increased with word-visibility and correlated with performance. TMS applied to motion-specialized area hMT+ disrupted reading performance for motion-dots, but not line-contours or luminance-dots. A quantitative model describes feature-convergence in! the VWFA and relates VWFA responses to behavioral performance. These findings suggest how visual feature-tolerance in the reading network arises through signal convergence from feature-specialized cortical areas.
• Development of a Method for the Purification and Culture of Rodent Astrocytes
  - Neuron 71(5):799-811 (2011)
  The inability to purify and culture astrocytes has long hindered studies of their function. Whereas astrocyte progenitor cells can be cultured from neonatal brain, culture of mature astrocytes from postnatal brain has not been possible. Here, we report a new method to prospectively purify astrocytes by immunopanning. These astrocytes undergo apoptosis in culture, but vascular cells and HBEGF promote their survival in serum-free culture. We found that some developing astrocytes normally undergo apoptosis in vivo and that the vast majority of astrocytes contact blood vessels, suggesting that astrocytes are matched to blood vessels by competing for vascular-derived trophic factors such as HBEGF. Compared to traditional astrocyte cultures, the gene profiles of the cultured purified postnatal astrocytes much more closely resemble those of in vivo astrocytes. Although these astrocytes strongly promote synapse formation and function, they do not secrete glutamate in response ! to stimulation.