Brief Communications in 2015

Neuropathic pain poses a major healthcare burden. The authors show that a specific set of neurons in the nucleus accumbens, a region long associated with affect, were changed in a mouse model of neuropathic pain. A pharmacotherapy that is well tolerated in man reversed these adaptations and alleviated pain.

The authors used a reversible inactivation technique that has not been used before in Old World monkeys, inhibitory chemogenetic receptors (DREADDs), to demonstrate that disconnecting a large region of monkey prefrontal cortex (orbitofrontal cortex) from a region in the temporal lobe (rhinal cortex) reduces sensitivity to differences in reward size.

Mesolimbic dopamine has been implicated both in reward prediction and in promoting movement. This study demonstrates that the patterns of dopamine release in the nucleus accumbens core are shaped by the initiation of appropriate reward-guided actions and prospective response accuracy, and not just prediction errors.

Immunotherapy with antibodies targeting the amyloid-β peptide has yet to show any cognitive benefit in Alzheimer's disease patients in clinical trials. In vivo two-photon imaging in mouse models of Alzheimer's disease now reveals that these antibodies do not alleviate neuronal dysfunction and can even worsen it.

Endogenous neural stem cells in the adult hippocampus are generally considered to be bi-potent. The authors show in mouse that inactivation of neurofibromin 1 (Nf1), a gene that is mutated in neurofibromatosis type 1, unlocks a latent oligodendrocyte lineage potential of neural stem cells to produce all three lineages in vivo.

Using functional MRI and a novel model-based analysis, the authors find that the uncertainty in sensory representations can reliably be estimated from trial-by-trial activity in human visual cortex. Moreover, this uncertainty represented in cortical activity affects the way people make decisions.

The authors show that episodic-memory representations progressively increase in scale along the hippocampal long axis, akin to the gradient of encoded space in the rodent hippocampus. They propose that this coding mechanism may enable the formation of memory hierarchies.

The amygdala is known to process information about faces, but it has remained unclear whether eye gaze is also encoded. Recording single neurons in the amygdalae of neurosurgical patients, the authors found responses to identity of the faces, but not to gaze direction.

Anorexia nervosa provides a compelling example of persistent maladaptive behavior: the severe restriction of caloric intake. Activity in the dorsal striatum was greater in patients than in controls during food choice and correlated with subsequent caloric intake, suggesting that dorsal fronto-striatal circuits are involved in this disorder.

People with autism are known for their inflexible behavior. Using a perceptual learning protocol, the authors demonstrate initially efficient learning in observers with autism, followed by anomalously poor learning when the target location is changed (over-specificity). Furthermore, over-specificity can be circumvented by a specifically designed protocol that reduces stimulus repetitions.

This protein quantitative trait analysis in monocytes evaluates cross-talk between Alzheimer risk loci and finds that the NME8 locus influences PTK2B, the CD33 risk allele leads to greater TREM2 expression, and the TREM1 risk allele is associated with a decreased TREM1/TREM2 ratio.

Using data from the Human Connectome Project, a single holistic multivariate analysis identified one strong mode of population co-variation: subjects were predominantly spread along a single ‘positive-negative’ axis linking lifestyle, demographic and psychometric measures to each other and to a specific pattern of functional brain connectivity.

Misfolded Aβ proteins can form proteopathic seeds that drive initiation, progression, and spreading of amyloidosis in the brain. Jucker and colleagues report that Aβ seeds can persist in mouse brain for months in the absence of host-derived Aβ and can then regain propagative and pathogenic activity in the presence of host Aβ.

C9orf72 mutations are the most common cause of amyotrophic lateral sclerosis and frontotemporal dementia. With unbiased screens in Saccharomyces cerevisiae, Jovicic et al. identified potent modifiers of toxicity of dipeptide repeat proteins produced by unconventional translation of the C9orf72 repeat expansions, pointing to nucleocytoplasmic transport impairments as potential disease mechanisms.

Humans learn about people and objects through positive and negative experiences, yet they can look beyond rewards to encode trait-level attributes such as generosity. The authors show that neural activity and choices reflect feedback-based learning about rewards and traits of people and slot machines and that trait learning strongly drives decisions about new social interactions.

It is widely assumed that D1 and D2 dopamine receptor-expressing striatal neurons code for discrete pathways in the basal ganglia. Combining optogenetics and electrophysiology, the authors show that this output architecture does not apply to nucleus accumbens neurons. Current thinking attributing D1/D2 selectivity to accumbens projections thus should be reconsidered.

A large literature has demonstrated the important role of spinal microglia in chronic pain processing. This paper demonstrates that microglia are required in male but not female mice. In female mice, a similar function appears to be subserved by adaptive immune cell, likely T lymphocytes.

The authors show that changes in nuclear dynamics of p75^NTR by γ-secretase cleavage are a novel molecular switch that determines TGF-β signaling in astrocytes. Cleaved p75^NTR acts as a component of the nuclear pore complex, regulating nuclear import of Smad-2 in astrocytes. The authors find that p75^NTR is required in mice for TGF-β-induced glial scar formation and reduced neuronal activity.

Genetic risk scores derived from GWAS of psychotic disorders are greater in creative professionals unaffected by psychosis. This association cannot be explained by shared environment or education. Thus, a shared genetic architecture underlies the propensity for creativity and psychosis.

Chronic social stress has adverse behavioral consequences and can result in the development of depression in humans. Using a rodent social stress model, we report increased synaptic connectivity between the thalamus and striatum in susceptible mice that controls behavioral coping mechanisms relevant to depression.