Volume 18 Issue 10, October 2015

It is a truism that the brain influences the body and that peripheral physiology influences the brain. Never is this clearer than during stress, where the subtlest emotions or the most abstract thoughts can initiate stress responses, with consequences throughout the body, and the endocrine transducers of stress alter cognition, affect and behavior. For a fervent materialist, few things in life bring more pleasure than contemplating the neurobiology of stress.

In their Perspective, Hariri & Holmes consider unique features of translational research on stress-related disorders that have helped fuel a productive dialogue from bench to bedside and back, as well as sparked important advances in identifying novel risk biomarkers and therapeutic strategies.

The brain perceives and adapts to stressors via multiple interacting molecular mechanisms involving the cell surface, cytoskeleton and epigenetic regulation resulting in structural remodeling, with continually changing gene expression. Understanding mechanisms of plasticity and vulnerability facilitate development of intervention for anxiety and depressive disorders as well as age-related cognitive decline.

Severe stress impairs cognitive function, but enhances emotionality. This Review describes how stress triggers contrasting patterns of plasticity in the hippocampus, prefrontal cortex and amygdala, all brain areas that are involved in learning and memory. These features of stress-induced plasticity can have long-term consequences for the debilitating symptoms of stress-related disorders.

Research has revealed the molecular events that weaken connectivity in prefrontal cortical circuits during stress exposure. These events rapidly flip the brain from a reflective to reflexive state and may also contribute to degenerative changes in schizophrenia and Alzheimer's disease. This mechanistic understanding has translated to therapeutics for prefrontal disorders.

Hodes et al. discuss mounting evidence in humans and rodent models of depression that causally links increased inflammation to depression. They take the perspective that heightened inflammation is a risk factor for depression and suggest targeted therapeutics to reduce inflammation as a novel approach to antidepressant treatment.

A mechanistic understanding of anxiety is required to advance the development of next-generation therapies for anxiety disorders. In this Review, Calhoon and Tye discuss recent insights into the circuit physiology driving anxiety-like behavior gained through the application of modern approaches in neuroscience.

In this Review, Hollon, Burgeno and Phillips discuss recent studies providing mechanistic insight into how stress alters circuitry involved in reward-related learning and motivation, as well as work examining how acute and chronic stress affect action selection in both rodents and humans.

In this review, Bale and Epperson discuss the importance of sex differences in stress found at all stages of life. As stress dysregulation is the most common feature across neuropsychiatric diseases, understanding sex differences in stress pathway development and maturation may predict disease risk and resilience factors across the lifespan.

Environmental influences affect the brain and mental health and often are social or have social components, even the more complex societal or area-level exposures. This Review discusses the neural correlates of adverse and protective social influences and argues that innovative methods may provide ecologically more valid insights in social neuroscience.

As conversion of odor signals to a two-dimensional map of activated glomeruli in the olfactory bulb is the key to odor recognition, decoding and deorphanizing of odorant receptors in the olfactory map is of great interest. Two genome-wide techniques now offer the ability to pair any odorant with its receptors.

How do fundamental synaptic processes in specific neuron populations drive behavior? A new study links a reduction of tonic inhibitory GABA current in a subset of central amygdala neurons to anxiety after fear conditioning.

A new study shows that an efficient allocation of sensory resources can lead to Bayesian estimates that are biased away from the prior, accounting for effects such as the bias toward oblique angles in orientation perception.

Dendrite arbor morphology is critical for neuron function. Yalgin and colleagues find that the activity of Centrosomin, used to build the mitotic spindle, is recycled after mitosis in dendrites. Centrosomin shapes the arbor by engaging microtubule nucleation at dendritic Golgi outposts to orient microtubule polarization in nascent branches.

Using awake and freely behaving mice, this study employs a high-throughput in vivo RNA-seq approach to identify odorant receptor repertoires. The authors find sets of odorant receptors for two odorants encompassing 69 odorant receptor-odor pairs and develop models to predict receptor activation.

Based on the finding that the concentration of mRNA encoding olfactory chemoreceptors decreases after odorant stimulation, the authors developed a large-scale transcriptomic approach that allows the identification of ligand-chemoreceptor pairs in various species in vivo. This represents a critical step in our understanding of combinatorial coding of odors.

Memory formation requires gene transcription, but the link between synaptic activity and transcription is not fully understood. Brd4 regulates transcription in other cell types and Brd4 family inhibitors are in clinical trials for cancer. The authors show that Brd4 is important for activity-dependent gene transcription in neurons and memory consolidation.

The optimal disambiguation of similar sensory stimuli by neuronal networks is essential to adapt animal behavior. Gschwend and colleagues show that the olfactory bulb network acts as a pattern separator, increasing slight differences between highly related odors. Inhibitory interneuron activation causally improves pattern separation and facilitates odor discrimination learning.

The locus coeruleus is a major neuromodulatory center for the mammalian brain. Here, the authors show that presenting sounds when locus coeruleus is active leads to enduring modifications of responses in auditory cortex and locus coeruleus. These synaptic and spiking changes have a profound effect on auditory perception for weeks.

Less is known about the role of amygdala circuits in anxiety than in acute fear responses. In this study, the authors demonstrate that aversive experience induces anxiety in mice by regulating the excitability of a defined subset of central amygdala neurons via extrasynaptic α₅ GABA_A receptors.

How does the brain stop a planned action that has suddenly become inappropriate? Here, Mayse et al. identify a novel subcortical mechanism of inhibitory control in the basal forebrain outside the canonical fronto-basal-ganglia circuit. Basal forebrain neuronal inhibition enables rapid behavioral stopping and also determines its speed.

The authors present a new observer model that combines efficient (en)coding and Bayesian decoding. The model makes the seemingly ‘anti-Bayesian’ prediction that perception can be biased away from an observer's prior expectations. Psychophysical data that previously were difficult to explain are well-matched by the model's prediction.

ScaleS is a tissue clearing method for light and electron microscopy featuring stable tissue preservation for immunochemical and genetic labeling of tissue for 3D signal rendering. The technique enables quantitative and reproducible reconstructions of aged and diseased tissue in animal models and patients for high resolution optical pathology.

Stress serves an important purpose in maintaining health, but prolonged or severe stress can be harmful, particularly to the central nervous system. Nature Neurosciencepresents a special issue focused on how stress affects brain function, behavior, and the development of psychiatric diseases, via a series of reviews and perspectives written by leaders in the field.