Explore the vast range of titles available.

The NIH BRAIN Initiative will build on recent successes in neuroscience to create and apply new tools for understanding brain activity. On 2 April 2013, President Barack Obama announced the Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative. In front of some 200 scientists in the East Room of the White House, the President declared, “…there is this enormous mystery waiting to be unlocked, and the BRAIN Initiative will change that by giving scientists the tools they need to get a dynamic picture of the brain in action and better understand how we think and how we learn and how we remember. And that knowledge could be—will be—transformative” ( 1 ).

The development of the sympathetic nervous system can be divided into three overlapping stages. First, the precursors of sympathetic neurons arise from undifferentiated neural crest cells that migrate ventrally, aggregate adjacent to the dorsal aorta, and ultimately differentiate into catecholaminergic neurons. Second, cell number is refined during a period of cell death when neurotrophic factors determine the number of neuronal precursors and neurons that survive. The final stage of sympathetic development is the establishment and maturation of synaptic connections, which for sympathetic neurons can include alterations in neurotransmitter phenotype. Considerable progress has been made recently in elucidating the cellular and molecular mechanisms that direct each of these developmental decisions. We review the current understanding of each of these, focusing primarily on events in the peripheral nervous system of rodents.

To study the brain from molecules to behaviour, neuroscientists face the challenge of communicating an emerging wealth of information in coherent accessible forms

When the sympathetic nerves that innervate rat sweat glands reach their targets, they are induced to switch from using norepinephrine as their neurotransmitter to acetylcholine. Catecholamines (such as norepinephrine) released by nerves growing to the sweat gland induce this phenotypic conversion by stimulating production of a cholinergic differentiation factor [sweat gland factor (SGF)] by gland cells. Here, culture of gland cells with sympathetic, but not sensory, neurons induced SGF production. Blockage of $\\alpha_1$- or β-adrenergic receptors prevented acquisition of the cholinergic phenotype in sympathetic neurons co-cultured with sweat glands, and sweat glands from sympathectomized animals lacked SGF. Thus, reciprocal instructive interactions, mediated in part by small molecule neurotransmitters, direct the development of this synapse.

To determine the role of the p75 neurotrophin receptor (p75 NTR ) in sympathetic neuron development, we crossed transgenic mice with mutations in p75 NTR , nerve growth factor (NGF) and neurotrophin-3 (NT-3). Neuron number is normal in sympathetic ganglia of adult p75 NTR–/– mice. Mice heterozygous for a NGF deletion (NGF +/– ) have 50% fewer sympathetic neurons. In the absence of p75 NTR (p75 NTR–/– NGF +/– ), however, neuron number is restored to wild-type levels. When NT-3 levels are reduced (p75 NTR–/– NGF +/– NT3 +/– ), neuron number decreases compared to p75 NTR–/– NGF +/– NT3 +/+ . Thus, without p75 NTR , NT3 substitutes for NGF, suggesting that p75 alters the neurotrophin specificity of TrkA in vivo .

Deficiencies in methods reporting in animal experimentation lead to difficulties in reproducing experiments; the authors propose a set of reporting standards to improve scientific communication and study design. Making the most of animal studies Animal studies have contributed immensely to our understanding of diseases and assist the development of new therapies, but inadequate experimental reporting can sometimes render such studies difficult to reproduce and to translate into the clinic. This year, a US National Institute of Neurological Disorders and Stroke workshop addressed this issue, and its conclusions are discussed in a Perspective piece in this issue of Nature . The main workshop recommendation is that at a minimum, studies should report on randomization, blinding, sample-size estimation and how the data were handled. The US National Institute of Neurological Disorders and Stroke convened major stakeholders in June 2012 to discuss how to improve the methodological reporting of animal studies in grant applications and publications. The main workshop recommendation is that at a minimum studies should report on sample-size estimation, whether and how animals were randomized, whether investigators were blind to the treatment, and the handling of data. We recognize that achieving a meaningful improvement in the quality of reporting will require a concerted effort by investigators, reviewers, funding agencies and journal editors. Requiring better reporting of animal studies will raise awareness of the importance of rigorous study design to accelerate scientific progress.

Cultured sympathetic neurons contain an excitatory transmitter, norepinephrine, and one that is inhibitory, acetylcholine. A new paper shows that BDNF increases the ratio of acetylcholine to norepinephrine release, reversing the effect of neural stimulation from excitation to inhibition.

We, the directors of the 27 NIH institutes and centers, wanted to respond to the points made by Andrew Marks in his recent editorial. While we appreciate that the scientific community has concerns, the current initiatives and directions of the NIH have been developed through planning processes that reflect openness and continued constituency input, all aimed at assessing scientific opportunities and addressing public health needs.