Volume 15 Issue 8, August 2012

Mice lacking NMDA receptors in the dentate gyrus and CA1 subfields of the hippocampus form spatial memories just as well as wild-type mice, but they disregard them when confounded by ambiguous local cues. Hippocampal NMDA receptors may influence spatial memory more subtly than previously thought.

Natural or artificially induced electrical activity changes can alter ion balance so as to briefly influence firing. An optogenetics study delineates one mechanism: Cl⁻ shifts causing seconds-long excitability changes after silencing.

Hypothalamic neurons that express agouti-related protein have been thought to regulate appetite by counteracting the melanocortin signaling pathway. Evidence now indicates that these neurons can also modulate dopamine signaling.

A study reveals that aged mice have decreased hippocampal expression of the DNA methyltransferase Dnmt3a2; re-expression in aged mice reverses memory deficits, and knockdown in young mice impairs memory formation.

Although the nervous and immune systems have been classically considered to modulate physiologically distinct functions, recent evidence points to coordinated activities during neurogenic inflammation. In this perspective, the authors examine the interactions between the peripheral nervous system and the immune response during health and disease.

Neuropathic pain often results from trauma or insult to peripheral nerves. In this Perspective, the authors examine recent evidence that implicates the microglia-expressed purinergic receptor P2X4 in the induction of neuropathic pain and suggest that this pathway marks a spinal mechanism distinct from those that mediate acute or inflammatory pain.

Multiple sclerosis is a debilitating inflammatory demyelinating disease of the CNS. In this perspective, the author examines the strengths and weaknesses of the numerous animal models that are currently being used to analyze the pathogenesis of this disease with an eye toward the precise pathological aspect that each model recapitulates.

Immune cells participating in CNS inflammation are now known to mediate both beneficial and detrimental effects. In this review, the authors examine the recently discovered bidirectional relationship between immune cells and neural stem cells and how these interactions may influence brain repair and provide new therapeutic targets.

Acute exposure to a variety of pathogens or inflammatory insults leads to a well-characterized set of responses in the CNS, aimed at promoting the clearance of the infecting agent. In this review, the authors examine the various symptoms of this 'sickness syndrome' and the actions of prostaglandins in linking inflammation with these CNS responses.

Despite being protected by the blood-brain barrier, the CNS must constantly be monitored for insult or pathogen invasion. In this review, the authors illustrate the molecular and cellular players that preside over this surveillance of the brain and spinal cord.

In this study, the authors show that optogenetic silencing of neurons with a commonly used light-driven chloride pump can result in alterations in GABAergic synaptic transmission that persist after the stimulation period and that may result in changes to neuronal excitability.

The projection from the lateral habenula (LHb) to the rostromedial tegmental nucleus (RMTg) transmits negative reward–related information. Here the authors show that aversive stimuli increase LHb excitatory drive onto RMTg neurons, and optogenetic stimulation of this pathway is sufficient to induce active, passive and conditioned behavioral avoidance.

AgRP neurons in the hypothalamus elicit feeding behavior. Here the authors show that interfering with AgRP neuron function, either by selective knockout of Sirt1 or by early postnatal ablation, leads to increased exploratory behavior and enhanced response to cocaine, which is associated with increased forebrain dopamine levels.

The authors find that aged mice have decreased expression of the DNA methyltransferase Dnmt3a2 in the hippocampus. Rescue of Dnmt3a2 expression in aged mice reversed learning and memory deficits, whereas decreasing Dnmt3a2 expression in young mice impaired memory formation.

Here the authors find that auditory cues presented quietly during a nap influence motor sequence learning. When one of two sequences was cued following initial learning, performance was disproportionately improved for that sequence, reflecting sleep-based reactivation and consolidation of skill memory.

In a longitudinal brain imaging study, patients with subacute back pain were followed over the course of 1 year. Initially greater functional connectivity of nucleus accumbens with prefrontal cortex predicted pain persistence, implying that corticostriatal circuitry is causally involved in the transition from acute to chronic pain.

The authors show that the microRNA miR-7a fine-tunes the expression of the transcription factor Pax6, generating a dorsal-ventral gradient that controls differentiation of olfactory bulb precursors into dopaminergic neurons.

In this study, the authors show that neocortical neural precursor cells exhibit progressively condensed chromatin as they lose neurogenic potential during development. Furthermore, the open chromatin state of early stage progenitors is regulated by the high mobility group A (HMGA) proteins.

In this study, the authors show that spontaneous calcium spiking activity in thalamocortical neurons modulates the rate of axonal growth during development via regulation of Robo1 transcription.

This study describes burst-dependent protection from synaptic depression, which maintains responsiveness to behaviorally important stimuli in Aplysia. In this attention-like mechanism, PKC at sensory neuron synapses discriminates the precise pattern of firing, preventing these release sites from becoming silenced during repeated tactile stimuli when these stimuli are salient.

Using a novel spatial discrimination task, Bannerman and colleagues show that mice lacking hippocampal NMDA receptors in dentate gyrus and CA1 can encode and store spatial memories normally but fail to use this spatial knowledge to select appropriate responses from ambiguous choices.

The authors found that, when monkeys detected a salient stimulus defined purely by bottom-up factors, neurons in the dorsolateral prefrontal cortex represented the stimulus no later than those in the posterior parietal cortex. The results suggest an early involvement of the prefrontal cortex in the bottom-up guidance of visual attention.

By tracking brain activity in both normal subjects and in epilepsy patients, the authors demonstrate that there are differences in the time courses of activation to a memory task in the perirhinal cortex and the hippocampus. These results suggest differentiated roles for these two areas during memory tasks.

Damage or disease in the nervous system is often accompanied by inflammation and an immunological response which requires a carefully choreographed and reciprocal interplay between the neural and immune systems. Recent work examining these interactions has begun to shed some light on the molecular mechanisms and circuitry which regulate how the brain responds to and, in some cases, modulates inflammation. Nature Neurosciencepresents a special focus issue on neuro-immune interactions which highlights some of the most recent and interesting research aimed at understanding the relationship between neural processes and immune reactions via a series of reviews or opinionated articles commissioned from key leaders in the field.