Review Articles in 2016

Recently, robust identification of hundreds of genetic variants associated with risk for neuropsychiatric disease has prompted new challenges in understanding their biological impact within an individual. The authors provide a framework for interpretation of genetic risk variants to uncover disease mechanisms and facilitate therapeutic development.

Animal models have failed to yield new treatments for psychiatric disorders. Some psychiatric disorders may result from pathology in plasticity mechanisms. Therefore, understanding plasticity mechanisms in model systems may provide insight into the disordered processes in patients.

Autism spectrum disorders are highly heterogeneous and include both idiopathic and syndromic forms. Sztainberg and Zoghbi discuss insights gained from studying syndromic autism spectrum disorders and their potential contribution to our understanding of the molecular pathways critical for normal cognitive and social development, as well as the relevance to idiopathic autism.

Functional studies of neuronal assemblies that encode memories have progressed dramatically due to recent technological advances. This review shows how a focus on assembly formation and consolidation provides a powerful conceptual framework to relate mechanistic studies of synaptic, neuronal and circuit plasticity to behaviorally relevant aspects of learning and memory.

Deficits in developmental synaptic pruning are frequently observed in autism. Here the authors demonstrate molecular pathways shared by pruning and long-term depression (LTD), a synaptic memory mechanism in adult brains that is dysregulated in autism. Thus, autism-related pruning deficits may result from the inability to weaken or disconnect inefficient synapses.

Extracellular electrophysiology and calcium imaging are powerful methods for recording neuronal populations. Yet both methods are subject to confounds that, if not accounted for, could lead to erroneous scientific conclusions. The authors discuss these confounds, strategies for identifying and ameliorating them, and potential research that could accurately calibrate population recording.

Ji et al. review emerging microscopy technologies that enable large-volume imaging of neural circuits. Focusing on two-photon fluorescence microscopy, they explored critical factors that limit imaging speed and restrict image volume, and also discuss three-dimensional imaging methods and their applications in rapid volume imaging of neural activity.

Although single-cell gene expression profiling has been possible for the past two decades, a number of recent technological advances in microfluidic and sequencing technology have recently made the procedure much easier and less expensive. Awatramani and colleagues discuss the use of single-cell gene expression profiling for classifying neuronal cell types.

This paper describes an integrated approach for neuroimaging data acquisition, analysis and sharing. Building on methodological advances from the Human Connectome Project (HCP) and elsewhere, the HCP-style paradigm applies to new and existing data sets that meet core requirements and may accelerate progress in understanding the brain in health and disease.

Genetically encoded indicators of neuronal activity have diversified and improved in performance in recent years, becoming essential tools for neuroscientists. Lin and Schnitzer review indicators for pH, neurotransmitter, voltage and calcium, with an emphasis on quantifying key indicator attributes and relating them to their applications in neuroscience.

Pericytes are vascular mural cells embedded in the basement membrane of brain microvessels that, in the CNS, are uniquely positioned in the neurovascular unit between endothelial cells, astrocytes and neurons. Here the authors examine the key signaling pathways between pericytes and their neighboring cells regulating CNS functions in health and disease.

The prefrontal cortex supports the expression and inhibition of fear- and reward-related behaviors. These dualities are attributable to discrete functional domains making up this brain region, which allow it to stimulate or inhibit behavior depending on an organism's experiences. The authors review evidence that supports, or refutes, this “go/stop” function.

The neurobiology of social behavior is highly complex and defects are present in several mental illnesses. Here Barak and Feng discuss neurobiological aspects of two neuropsychiatric disorders presenting opposite social behavior abnormalities, autism spectrum disorder and Williams syndrome.

In this Review, a collaboration of leading experts in amyotrophic lateral sclerosis (ALS) research present the state of the field regarding the use patient-derived induced pluripotent stem cells to generate motor neurons in vitro. Motor neuron characterization, including transcriptomics, molecular markers, neuron function and electrophysiology, are discussed in the context of maturation and disease.

The complexity of problems and data in psychiatry requires powerful computational approaches. Computational psychiatry is an emerging field encompassing mechanistic theory-driven models and theoretically agnostic data-driven analyses that use machine-learning techniques. Clinical applications will benefit from relating theoretically meaningful process variables to complex psychiatric outcomes through data-driven techniques.

The state of the nervous system shifts constantly. Most studies focus on how state determines the average neural response, with little attention to the trial-to-trial fluctuations of brain activity. We review recent theoretical advances in modeling the physiological mechanisms responsible for state-dependent modulations in the correlated fluctuations of neuronal populations.

What are the challenges associated with storing information over time in the brain? Here the authors explore the computational principles by which biological memory might be built. They develop a high-level view of shared problems and themes in short- and long-term memory and highlight questions for future research.

Despite representing a minority of cortical cells, inhibitory neurons deeply shape cortical responses. Inhibitory currents closely track excitatory currents, opening only brief windows of opportunity for a neuron to fire. This explains the variability of cortical spike trains, but may also, paradoxically, render a spiking network maximally efficient and precise.

Dynamic membrane transformations are not exclusively controlled by cytoskeletal rearrangement, but also by biophysical constraints, adhesive forces, membrane curvature and compaction. Recent technological advances have helped clarify longstanding controversies concerning myelination, from target selection to axon wrapping and membrane compaction. Chang et al. review these findings and discuss how understanding these processes provides insight into myelination-centered mechanisms of neural plasticity.

Central melanocortinergic signaling via the melanocortin-4 receptor is both a culprit in and a target for obesity. The authors review our understanding of this evolutionarily conserved system in the regulation of mammalian energy homeostasis.