Volume 16 Issue 12, December 2013

The cerebellum, with its stereotypic anatomy, has served as an engine of discovery for developmental neurobiologists and cancer biologists alike. However, new findings reported in this issue of Nature Neuroscience suggest that its anatomy and cellular specification, and by extension, its tumor biology, may be less simple than previously believed.

A study in this issue of Nature Neuroscience demonstrates that astrocytic transforming growth factor-β facilitates complement-mediated removal of weak synapses by microglia during the synaptic pruning period.

In synaptic integration, timing is everything. A new study demonstrates that voltage-activated ion channels transform spatially distributed synaptic input into a coherent neuronal output by countering time delays in the dendritic tree.

Errors are typically followed by more cautious responses. A study now provides evidence that remarkably conserved neural dynamics underlie these post-error adjustments to behavior in rodents and humans.

In this review, the author brings together research on the neuro-computational basis of decision-making and the homeostatic regulation of feeding behavior, emphasizing what is unique about feeding decisions, and how homeostatic signals influence the decision-making circuitry.

In this study, the authors show that the mouse ortholog of the amyotropic lateral sclerosis/frontotemporal dementia (ALS/FTD)-associated human locus C9ORF72 exhibits highly enriched expression in the neuronal cell types that show susceptibility during the disease. These findings suggest a potential explanation for the cell selectivity observed in ALS/FTD.

This study shows that neural progenitor cells in the adult hippocampus of mice receive immature GABAergic synaptic inputs from parvalbumin (PV)-expressing interneurons, and uses optogenetic stimulation to demonstrate local PV interneuron activation via GABA signaling promotes survival and maturation of newborn neurons.

In this paper the authors demonstrate that functionally independent populations of neurons in the ventromedial hypothalamus (VMH), a region implicated in feeding, sex, and aggression, are essential for predator and social fear in mice.

Here the authors show that optogenetic stimulation of Purkinje cells, the sole output neurons of the cerebellar cortex, can drive motor learning in mice. This represents an additional instructive signal for the induction of learning, beyond climbing fibers, that can expand the learning capacity of motor circuits.

In this study, the authors show that a subset of cerebellar granule neurons originate not from the granule neuron precursors (GNPs) but from a population of Nestin-expressing progenitors (NEPs) in the deep external germinal layer. In addition, they find that these NEPs are more susceptible to Sonic Hedgehog–induced genomic instability and tumor formation.

The neurodegeneration found in human ataxia-telangiectasia (A-T) is caused by mutations in the ATM (A-T mutated) gene. Li et al. have identified the polycomb group protein with histone methyltransferase activity called EZH2 as a target of the ATM kinase. The study shows that ATM deficiency increases EZH2 stability, thus increasing methylated histone marks. This results in epigenetic changes in transcription that compromise the health and survival of CNS neurons.

This study shows that spontaneous opening of presynaptic voltage-gated calcium channels (VGCCs) is a major trigger of action potential independent synaptic vesicle release, and finds that R-type channels contribute disproportionately, consistent with a relatively negative activation threshold. The authors also use Ca²⁺ chelation experiments and computational modeling to reconcile how transient Ca²⁺ nanodomains evoked by VGCC opening trigger both spontaneous and action potential evoked neurotransmission.

Electrical coupling in the brain usually occurs between inhibitory neurons that are anatomically and functionally similar. Here the authors show that the excitability of inhibitory interneurons in the dorsal cochlear nucleus is controlled by electrical synapses with excitatory projection cells.

In this study, the authors show that, during the retinogeniculate refinement period, astrocyte-derived TGF-β regulates the expression and synaptic localization of C1q, a classical complement protein. They find that TGF-β signaling and C1q expression in neurons are key regulators of microglia-mediated synaptic pruning in the dorsal lateral geniculate nucleus.

The authors find that GABA_AR-mediated tonic currents recorded in rodent cerebellar granules cells can be modulated by ethanol in opposite directions in different strains exhibiting opposite preferences in alcohol consumption. These differences in ethanol sensitivity across strains are linked to differential levels of expression of presynaptic neuronal nitric oxide synthase and postsynaptic PKC activity.

The authors find that ACR-23, a ligand-gated cation channel of the cys-loop family, is a betaine receptor and is expressed in worm mechanosensory neurons involved in stimulating locomotion. Excessive activation of ACR-23 leads to paralysis and is responsible for the nematocidal properties of betaine. The authors also find that the action of betaine on ACR-23 is allosterically potentiated by the aminoacetonitrile derivative monepantel, a new antihelminthic drug.

The authors investigated the mechanisms underlying hippocampal sharp waves. They found that CA3 axo-axonic cells (AACs) stopped firing during sharp waves in vivo. They also identified GABAergic cells in the medial septum that are activated during sharp waves and project to CA3; these cells may inhibit AACs during sharp waves.

Pyramidal cells have to integrate thousands of inputs across their expansive dendritic arbors. The spatial spread of these inputs should lead to intraneuronal propagation delays. Here the authors show that the distribution of HCN channels in hippocampal pyramidal cells normalizes these delays, particularly for inputs at theta and gamma frequencies.

The authors use dendritic imaging to examine odor response properties of individual synaptic sites of mushroom body neurons. They find that mushroom body neurons receive input from different glomerular channels and require several of those inputs to be co-active to spike, a likely foundation for their remarkable stimulus selectivity.

Saha and colleagues measured the spatiotemporal dynamics of odor representations across populations of neurons in the locust olfactory system during the presentation of two overlapping odors. They report that the performance of locusts in a background-independent odor recognition task is correlated with the ability to decode foreground odor identity from the population activity, suggesting the existence of a background-invariant population code for odorants in this system.

Diverse species use ineraural time differences to locate the origin of sounds in space. Here the authors show that GABA_B receptor–mediated feedback onto the medial superior olive modulates the gain of auditory space coding, leading to systematic shifts in the percept of sound location.

How do dendrites contribute to neuronal computations in intact circuits? Using dual whole-cell recordings from the soma and dendrites of retinal ganglion cells, Sivyer and Williams demonstrate that the engagement and inhibitory synaptic control of a cascade of active dendritic integration compartments underlies the computation of image motion by direction-selective rabbit retinal ganglion cells—placing dendritic integration at the heart of physiologically engaged neuronal-circuit operation.

Cholinergic transmission from the basal forebrain provides neuromodulatory control over brain states such as wakefulness and sleep. Here the authors show that cholinergic input bidirectionally and dynamically modulates cortical processing of sensory inputs and influences visual perception in awake, behaving mice.

The primary visual cortex (V1) carries signals related to visual speed, and its responses are also affected by run speed. Here the authors report that nearly half of the V1 neurons were reliably driven by combinations of visual speed and run speed. As a population, V1 neurons predicted a linear combination of visual and run speed better than visual or run speeds alone.

The authors study fMRI responses to colors and achromatic images to address the fundamental organizational principles of monkey inferior temporal cortex. They report color-biased regions adjacent and ventral to face patches, at locations predicted by a series of coarse eccentricity maps.

Attention alters neural responses that encode different aspects of visual stimuli, but exactly how these changes together modulate the encoded spatial representation of a scene remains unclear. Here the authors look at spatial priority maps of attended to and ignored stimuli and find that attention increases the gain but not the size of stimulus representations.

Adaptive control to improve performance after making mistakes in a given task is known to involve prediction error signaling in the anterior cingulate cortex (ACC). The current study examines adaptive control in humans and rats by using comparable time-estimation tasks for each organism, and the authors show that low-frequency oscillations within the ACC in humans and the medial frontal cortex (MFC) in rats are correlated with adaptive behavioral control. They also show that these frontal oscillations are phase locked to the oscillation in the motor regions in the brain and that inactivation of the MFC in rats can disrupt both behavioral control and oscillatory coupling.

In this Resource study, the authors used Direct RNA Sequencing (DRS) to quantitatively examine the transcriptional profile of microglia, focusing specifically on the proteins important for binding endogenous ligands and potential pathogens—a collection they term the 'sensome'. They also compare this profile to that of peripheral macrophages.