Volume 13 Issue 1, January 2010

A study in this issue presents a new mouse model that directly tests the glutamate hypothesis of schizophrenia. The study reports that a decrease in NMDA receptor signaling during a particular developmental window in interneurons can induce cellular and behavioral changes similar to those seen in schizophrenia.

A new study shows that the Na⁺/K⁺ ATPase can function as an integrator of spike activity and interacts with a K⁺ conductance to provide a cellular short-term memory of locomotion in the Drosophila larval motor circuit.

A study in this issue finds that the chemoattractant cue, Sonic Hedgehog, can activate a repulsive response of commissural axonal pathfinding to Semaphorins, thereby acting as a 'switch' in axon guidance.

The frontal pole cortex is thought to be the most complex of all frontal cortex areas. Overcoming technical obstacles to direct recordings, a study in this issue finds that neurons in this area have unexpectedly simple response properties.

The slow (<1 Hz) rhythm, the most substantial EEG signature of non–rapid eye movement (NREM) sleep, is generally viewed as originating exclusively from neocortical networks. The authors propose that this oscillation requires the interaction of a cortical oscillator and two thalamic ones.

Previous work has suggested that triggering transmitter release might require the opening of many Ca²⁺ channels. Here the authors show that at the inhibitory basket cell–granule cell synapse in rat hippocampus, the opening of three or fewer Ca²⁺ channels is sufficient to trigger transmitter release with high temporal precision.

In cultured rat hippocampal neurons, thrombospondin 1 hastened synapse formation via interaction with neuroligin 1.

Cue-evoked activity of midbrain dopamine neurons is proposed to encode the magnitude, delay and uncertainty of predicted rewards. Here the authors report that this activity separates costs and benefits, as it does not encode the costs of the action required to obtain predicted rewards.

Axonal pathfinding during development needs appropriate responses to various attractive and repulsive guidance cues. The exact mechanisms by which different attractant/repulsion machineries interact or how the switch is precisely regulated at appropriate location are unknown. Here, Parra and Zou find that Sonic Hedgehog (Shh) can turn on Semaphorin repulsion via Shh receptors Patched-1 and Smoothened via the PKA pathway.

This study shows that continuous synthesis and availability of the phosphoinositide PIP₃ at the postsynaptic terminal is necessary for synaptic transmission in rat hippocampal neurons. A slow but constant turnover of PIP₃ was required for maintaining postsynaptic AMPA receptor, but not NMDA receptor, clustering.

Mammalian cochlea inner hair cells (IHCs) can code a continuous grading of sound intensities. This is because neurotransmitter release at mature sensory ribbon synapses is linearly dependent on calcium influx, which has the effect of broadening the cells' dynamic range. Immature IHC neurotransmitter release is quite different. Here, the authors show that a switch from syanptogamin I and II to synaptogamin IV underlies this developmental change.

To keep track of input and output over a course of time, generation of rhythmic neuronal activity requires a form of spike counter. In this study, Pulver and Griffith show that electrogenic activity of Na⁺/K⁺ pump underlies afterhyperpolarization in Drosophila larval motor neuron, which can functions as an activity integrator and as an intrinsic mechanism of cellular short-term memory.

This study uses a new method of profiling cell type–specific gene expression to identify genes expressed in fruitfly clock neurons. Such profiling yields two novel circadian genes, in separate sets of clock neurons and with differing circadian functions.

Drosophila mutants that have defective Shaker K⁺ channel or SLEEPLESS, a GPI-anchored protein of Ly-6/neurotoxin family, have very short sleep cycles. Here the authors show that SLEEPLESS binds to Shaker to regulate its localization, membrane excitability and homeostatic sleep drive.

Nakazawa and colleagues describe a mouse strain in which the NR1 subunit of the NMDA receptor is selectively eliminated in cortical and hippocampal interneurons in early postnatal development. These mice have several behavioral deficits that are consistent with the theory that GABAergic dysfunction contributes to the pathology of several psychiatric disorders, including schizophrenia.

Information flow in the cortex is usually thought to be subserved by direct, cortico-cortical connections. Using optical imaging in a thalmocortical slice preparation, this study demonstrates a potent corticothalamocortical pathway from layer 5 of the S1 barrel field to S2 of the mouse somatosensory cortex.

Simple cell receptive fields (RFs) consist of spatially segregated 'On' and 'Off' subregions. Previous work suggested that excitatory inputs underlie this segregation. This study uses voltage clamp recordings in mouse to reveal that actually inibitory inputs are responsible for RF organization.

In rodents, descending corticospinal tracts can be rerouted to innervate new targets after a spinal cord injury. Here, Ghosh et al. show that such anatomical rearrangement in the injured spinal cord is accompanied by sensory remapping at the cortical level.

The authors report that the spiking history of small, randomly sampled ensembles of human and nonhuman primate cortical neurons can predict subsequent single neuron spiking. Spiking could be predicted by both local ensemble spiking histories as well as those in other cortical areas. These results provide evidence for strong collective cortical dynamics at the level of neuronal spikes.

People and animals are capable of making decisions using information about the probabilistic associations between a combination of cues and an outcome. Here the authors use computational theory to suggest that the posterior ratio, an important quantity for forming probabilistic inferences, can be learned and encoded by synapses that have bounded weights and undergo reward-dependent Hebbian plasticity.

Recording from single neurons in awake macaque monkeys, the authors find that neurons of the frontal pole cortex encode decisions at the time of feedback, but do not carry signals typically seen in other prefrontal areas, such as information about sensory cues, strategies, working memory, future goals or movement plans.

The authors describe cell-based neurotransmitter fluorescent engineered reporters (CNiFERs), a new biosensor for monitoring neurotransmitter receptor activation. CNiFERs are cells engineered to express both a metabotropic receptor that triggers the G_q protein–coupled receptor cascade to increase calcium concentrations and a genetically encoded fluorescent calcium sensor for visualization.

This Resource paper describes a set of five new reporter mice, derived from Rosa26, driving Cre-dependent strong and ubiquitous expression of fluorescent proteins. In particular, the new mice show clear and specific expression patterns in the adult brain. The mice are available through Jackson Laboratories, and growing expression datasets can be accessed at http://transgenicmouse.alleninstitute.org/.