Volume 19 Issue 9, September 2016

To highlight worldwide efforts to fund neuroscience research and address the growing threat of brain disorders, Nature Neuroscience asked leaders of six global brain initiatives to write about their programs.

Given recent advances in genome engineering technology like CRISPR and the difficulty of modeling human diseases in rodents, transgenic nonhuman primates may be used to develop etiologically relevant models of disease. This perspective by Guoping Feng et al. highlights the technological advances, potential challenges and opportunities these models present to furthering our understanding of disease.

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.

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.

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.

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.

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.

In vivo imaging of the spinal cord provides insights into the coding of skin temperature. Intriguingly, while heat-responsive dorsal horn neurons encode absolute temperatures, cold-responsive neurons report relative drops.

The inability of adults to retrieve episodic memories of infancy is referred to as infantile amnesia. A study now provides one of the first explanations of the neurobiological mechanisms underlying this phenomenon.

Even before a child learns to read, the future location of his or her letter-processing area can be predicted from its connections to the rest of the brain. Reading acquisition thus piggybacks on a pre-existing brain circuit.

The authors analyzed the exome sequences of 2,104 intellectual disability patients and their parents. They identified 10 novel candidate genes associated with specific clinical phenotypes.

In this study, the authors show that LTP lacks synapse specificity in hippocampi of aged (21–28 months) mice, possibly resulting from diminished levels of the K⁺/Cl⁻ cotransporter KCC2 and depolarizing GABA_A receptors. The KCC2 enhancer CLP257 restored synapse specificity of LTP, providing a possible new target for repairing memory loss in senescence.

Using in vivo spinal cord two-photon calcium imaging, the authors provide the first comprehensive characterization of the representations of temperature in the spinal cord and reveal that spinal neurons encode temperature change for cold and absolute temperature for heat.

The acquisition of a new skill or motor program is thought to be mediated by changes in neuronal plasticity at early stages of learning, which is later stabilized by new myelin generated by oligodendrocytes. In this study, the authors show that oligodendrocyte precursors exist in a ‘primed’ state, which allows them to contribute to early stages of motor learning.

Long-term depression at synapses between L4 and L2/3 neurons in somatosensory cortex is thought to require presynaptic NMDARs. In contrast, the present work finds that genetic deletion of postsynaptic but not presynaptic NMDARs blocks LTD and that the action of postsynaptic NMDARs appears to be metabotropic rather than ionotropic.

Infantile amnesia is the forgetting of memories in young children. In this paper, the authors show that in rats early life memories are not lost but rather stored in a latent form that can be retrieved later during adult life following exposure to appropriate reminders. The formation of these early memories requires the hippocampus and is subject to a developmental critical period that depends on mechanisms similar to those underlying critical periods in sensory systems.

Control of action selection in the brain must be stable yet flexible. Using two-photon calcium imaging, the authors find distinct population activity states in secondary motor cortex for different stimulus–response contingencies and show that transitions between these states occurred earlier when mice were required to abort a repetitive action and use a conditional rule.

Feedforward and feedback synaptic pathways shape how neural activity evolves across cortical areas, but they are difficult to monitor using traditional methods during behavior. The authors use pathway-specific and cellular-resolution in vivo imaging to quantify sensory and decision-related neural activity both within and propagating between two cortical areas critical for touch perception.

Before children can read, their brains have yet to develop selective responses to words. This study demonstrates that a child's connectivity pattern at age 5 can predict where their own word-selective cortex will later develop. This suggests that connectivity lays the groundwork for later functional development of cortex.

ALS patient iPSC-derived motor neurons aim to model disease phenotypes. The authors demonstrate that these cells transcriptomically resemble fetal rather than adult spinal motor neurons, and familial and sporadic forms of ALS disrupt gene networks and pathways associated with neuronal maturation and aging. These data provide a resource for further understanding how molecular changes in motor neurons lead to disease.