Reviews & Analysis

In the last 25 years, explosive interest has implicated the orbitofrontal cortex in nearly every function known to cognitive neuroscience. Yet scientific progress comes as much from questioning existing ideas as proposing new ones. This review discusses major theories of orbitofrontal function and the data that invalidate these ideas.

Head direction cells have been hypothesized to form representations of an animal's spatial orientation through internal network interactions. New data from mice show the predicted signatures of these internal dynamics.

Chronic cocaine exposure induces long-lasting, transcription-dependent changes in neuronal function. A genome-wide sequencing study shows how cocaine changes the epigenome to exert specific, long-lasting effects on neuronal transcription.

A study shows that reward and punishment have distinct influences on motor adaptation. Punishing mistakes accelerates adaptation, whereas rewarding good behavior improves retention.

Reductions in brain glucose metabolism have long been associated with Alzheimer's disease. A study now demonstrates that the endothelial glucose transporter GLUT1 is vital for maintaining brain energy metabolism and vascular clearance of amyloid-β.

Cortical circuits are shaped by sensory experience. These changes have now been visualized with single-synapse resolution in vivo, revealing clustered potentiation along stretches of dendrite.

Skilled behavior is thought to rely on the dorsal striatum. A study now reports that skills depend on striatal encoding of movement kinematics, linking learned sequences of movements with temporally distributed striatal activity.

Neurofeedback that tracks attentional focus in real time using fMRI and alerts subjects to impending lapses by modulating the difficulty of the task itself has been demonstrated to improve behavioral performance.

What drives us to pursue distant, more valuable goals over more proximate, lesser ones? Counter to what you might expect, this type of advanced goal-directed planning and foresight in primates may involve the amygdala. In a reward savings task, neurons in the amygdala track the length and subjective value of internally generated plans.

In this Perspective article, Brian Grone and Scott Baraban examine some of the numerous nonhuman animal models of epilepsy. The authors outline how traditional animal models have advanced our understanding of seizure initiation and epileptogenesis and also describe how the use of more 'non-traditional' model systems may further improve insight into both disease mechanisms as well as potential therapeutic avenues.

In this Review article, Jack Parent and Stewart Anderson discuss the advantages and limitations of using patient-derived cells, such as induced pluripotent stem cells, to probe the mechanisms of epileptogenesis and disease progression. In addition, they look at potential therapeutic avenues, such as cell-replacement strategies, that may arise from this field.

In this Review, Jeanne Paz and John Huguenard examine how recent work has informed us on the function of brain microcircuitry and how different circuit types may contribute to seizure generation and/or propagation. The authors also propose the idea that these microcircuits may regulate the spread of seizures and represent new targets for therapeutic intervention.

In this Review, Jeff Noebels examines recent advances in the identification of new genes underlying the onset of epilepsy. Given their functional convergence on synaptic inhibition and rich interactive landscape, collective analysis of genes driving major network interactions—as performed in the cancer field—may help point the way forward toward better diagnostics and target prioritization.

Current treatment options are, for many patients with epilepsy, either insufficient or ineffective and, thus, new therapeutic methodologies are necessary. In this Perspective, Esther Krook-Magnuson and Ivan Soltesz look at recent advances in optogenetic-based modulation of circuit activity and seizures with an eye toward the prospect - and challenges - of utilizing these technologies for the treatment of epilepsy.

The term ‘seizure’ emphasizes the abrupt and unpredictable nature of the onset of epochs of pathological neuronal synchrony that define the disorder of epilepsy. Mechanisms of epilepsy should account for seizure transitions with these unique temporal properties. In this review, Kevin Staley discusses how combining insights from new genetic etiologies with seizure timing may begin to outline the mechanisms by which the brain becomes predisposed to seizures.

Temporally coordinated signals at gamma frequencies and higher are often used to study inter-regional communication in brain networks, but interpreting mechanisms from population measures can be troublesome. The authors discuss the physiological origins of gamma coherence and suggest ways to decipher its roles in neural function.

The hippocampus, a structure critical for memory and navigation, contains both place and episodic cell assemblies. Synchronous input from the medial septum is crucial for inducing spatial and temporal neural sequences. These sequences are, in turn, necessary for constructing episodic cells and, in the absence of sensory input, place cells.

Spatial hearing in birds and mammals is more alike than previously thought in its patterns of developmental plasticity, physiological responses, and the computations employed to interpret binaural cues and map the environment.

Glutamate transporters influence the kinetics of synaptic transmission by acutely buffering synaptically released glutamate. In addition to high synaptic density of EAAT2, the transporter's high mobility contributes to function.