Articles in 2015

The authors use computational modeling of participants' performance on an aversive learning task to examine how decision-making is altered in anxiety. Results indicate that anxious individuals struggle to use information regarding the stability of action-outcome relationships to guide their choices. Pupillometry data link this deficit to altered norepinephrinergic function.

Glioblastomas contains stem-like tumor cells that display differential metabolic profiles. Here the authors show that brain tumor initiating cells contain fragmented mitochondria owing to activation of the key mediator of mitochondrial fission, DRP1, controlled by a competitive CDK5–CAMK2 axis. Targeting DRP1 activity attenuates growth of stem-like tumor cells, and activated DRP1 informs poor patient prognosis.

Winkler et al. show that the glucose transporter GLUT1 in brain endothelium is necessary for the maintenance of proper brain capillary networks and blood-brain barrier integrity. The study also shows that loss of GLUT1 in a mouse model of Alzheimer's disease accelerates BBB breakdown, perfusion and metabolic stress resulting in behavioral deficits, elevated amyloid beta levels and neurodegeneration.

Recording from population of head-direction cells across brain states, the authors provide experimental demonstration of the existence of internally organized attractor: the sequential activity of head direction neurons observed in the waking mouse persists during sleep, and this 'neuronal compass' always points toward well-defined directions.

The authors use TetTag pharmacogenetics to mark neuronal ensembles activated in the preoptic hypothalamus during dexmedeotomidine-induced sedation or recovery sleep. When these ensembles were selectively reactivated, NREM sleep and the accompanying drop in body temperature were recapitulated. Thus α₂ adrenergic receptor–induced sedation and recovery sleep share circuitry sufficient for producing these states.

Learning of arbitrary associations depends on the hippocampus and prefrontal cortex. This learning is reflected in prefrontal cortex. The hippocampus instead provides feedback about whether trial-and-error guesses are correct or incorrect. The two areas synchronize in different frequency bands following correct vs. incorrect guesses, which may guide learning.

Human motor adaptation is often described as an automatic process insensitive to reward- or punishment-based feedback. Contrary to this hypothesis, Galea et al. show through a double dissociation that negative and positive feedback have independent effects on the learning and retention components of motor adaptation, respectively. These results promise to have significant implications for the understanding and optimization of motor adaptation.

The authors show that inhibitory neurons of the pontine reticular formation (PRF) exert powerful control over the intralaminar thalamic nuclei, a major gate of forebrain motor centers. Optogenetic activation of inhibitory PRF terminals antagonizes voluntary movements and promotes slow cortical oscillations, highlighting the contribution of brainstem ascending projections to large-scale motor circuits.

In this study, the authors report the molecular characterization of orally bioavailable and blood-brain-barrier permeable inhibitors of the nuclear export molecule Xpo1/CRM1 and define the immunomodulatory and neuroprotective effects in preclinical models of inflammatory demyelination and excitatory neurotoxicity.

Lapses of attention are commonplace, potentially because they are detected too late to be prevented. The authors use real-time fMRI to provide participants continuous access to their attentional state. Real-time feedback, particularly from frontoparietal cortex, improved sustained attention abilities and modified representations in visual cortex and basal ganglia.

Neurogliaform interneurons constitute an essential component of cortical circuits. This paper provides evidence that, during early development, superficial neurogliaform cells of the primary somatosensory barrel field cortex receive prominent innervation from the thalamus. These afferents also activate postsynaptic NR2B-containing NMDA receptors, which are essential for the neurons' proper cortical integration.

Coincidence detection is a fundamental neural operation, developed to an extreme in the computation of interaural time differences for sound localization. This study utilizes intracellular in vivo recordings and pharmacological manipulations in the medial superior olive of Mongolian gerbil to reveal that maximal coincidence is not just determined by the timing of synaptic inputs, but also by intrinsic neural properties.

Dopamine axons projecting from the ventral tegmental area to the nucleus accumbens (mesoaccumbens axons) play a role in motivation. Tthe authors show that there are distinct microdomains releasing either dopamine or glutamate within individual mesoaccumbens axons in rats and mice.

Comprehensive analysis of epigenetic regulation demonstrates a series of complex, interacting chromatin mechanisms by which chronic exposure to opiates downregulates Bdnf gene transcription in the ventral tegmental area. This regulatory cascade is also shown to play a role in controlling opiate-induced behavioral plasticity.

Insertion of AMPA receptors into the synaptic membrane is thought to be a central mechanism for controlling experience-dependent changes in synaptic strength, yet this has never been observed in real time in the intact brain. Using two-photon imaging, Zhang and colleagues were able to provide this missing piece of information by tracking the insertion of GluA1 in spines in mouse barrel cortex neurons during repetitive whisker stimulation.

The authors investigated the role of glycinergic preBötC neurons in respiratory rhythmogenesis in mice using viral delivery of Channelrhodopsin-2 (ChR2) or Archaerhodopsin (Arch) genes. They conclude that glycinergic preBötC neurons modulate inspiratory pattern and are important for reflex apneas but that the rhythm can persist after significant dampening of their activity.

microRNAs control synaptic signaling through regulation of postsynaptic responsiveness. This study provides evidence that the conserved microRNAs miR-1000 and miR-137 act presynaptically via glutamate transporters to regulate glutamate release. miR-1000 expression is activity dependent, perhaps allowing activity to fine-tune the strength of excitatory synaptic transmission.

The authors recorded spiking activity in the sensorimotor striatum of rats performing a motor sequence in an automatic manner. They report continuous and integrative representation of contextual and kinematic information. Reversible perturbation of these representation increased execution variability, suggesting a strong contribution in constraining the execution motor habits.

The authors show that astrocytes produce high levels of the adenosine receptor A2A in Alzheimer brains. Reducing the levels of astrocytic A2A boosted memory in young and aging mice and mouse models of Alzheimer disease, whereas activating a related molecular pathway impaired memory. Thus, astrocytes regulate memory and abnormal receptor activity in these cells may contribute to memory disorders.

Combining single-neuron recordings and a multistep economic choice task in monkeys, the authors find activity in amygdala neurons that predicts the value and length of an internally planned choice sequence leading to future reward. Prospective amygdala activity appears to encode components of an internal plan and guide behavior over several steps towards self-defined, distant goals.