Continuing population and consumption growth will mean that the global demand for food will increase for at least another 40 years. Growing competition for land, water, and energy, in addition to the overexploitation of fisheries, will affect our ability to produce food, as will the urgent requirement to reduce the impact of the food system on the environment. The effects of climate change are a further threat. But the world can produce more food and can ensure that it is used more efficiently and equitably. A multifaceted and linked global strategy is needed to ensure sustainable and equitable food security, different components of which are explored here.

SummaryEnergy use, mainly to reverse ion movements in neurons, is a fundamental constraint on brain information processing. Trafficking of mitochondria to locations in neurons where there are large ion fluxes is essential for powering neural function. Mitochondrial trafficking is regulated by Ca2+ entry through ionotropic glutamate receptors, but the underlying mechanism is unknown. We show that the protein Miro1 links mitochondria to KIF5 motor proteins, allowing mitochondria to move along microtubules. This linkage is inhibited by micromolar levels of Ca2+ binding to Miro1. With the EF hand domains of Miro1 mutated to prevent Ca2+ binding, Miro1 could still facilitate mitochondrial motility, but mitochondrial stopping induced by glutamate or neuronal activity was blocked. Activating neuronal NMDA receptors with exogenous or synaptically released glutamate led to Miro1 positioning mitochondria at the postsynaptic side of synapses. Thus, Miro1 is a key determinant of how energy supply is matched to energy usage in neurons.

Although food prices in major world markets are at or near a historical low, there is increasing concern about food security—the ability of the world to provide healthy and environmentally sustainable diets for all its peoples. This article is an introduction to a collection of reviews whose authors were asked to explore the major drivers affecting the food system between now and 2050. A first set of papers explores the main factors affecting the demand for food (population growth, changes in consumption patterns, the effects on the food system of urbanization and the importance of understanding income distributions) with a second examining trends in future food supply (crops, livestock, fisheries and aquaculture, and ‘wild food’). A third set explores exogenous factors affecting the food system (climate change, competition for water, energy and land, and how agriculture depends on and provides ecosystem services), while the final set explores cross-cutting themes (food system economics, food wastage and links with health). Two of the clearest conclusions that emerge from the collected papers are that major advances in sustainable food production and availability can be achieved with the concerted application of current technologies (given sufficient political will), and the importance of investing in research sooner rather than later to enable the food system to cope with both known and unknown challenges in the coming decades.

Modification of the number of GABA A receptors (GABA A Rs) clustered at inhibitory synapses can regulate inhibitory synapse strength with important implications for information processing and nervous system plasticity and pathology. Currently, however, the mechanisms that regulate the number of GABA A Rs at synapses remain poorly understood. By imaging superecliptic pHluorin tagged GABA A R subunits we show that synaptic GABA A R clusters are normally stable, but that increased neuronal activity upon glutamate receptor (GluR) activation results in their rapid and reversible dispersal. This dispersal correlates with increases in the mobility of single GABA A Rs within the clusters as determined using singleparticle tracking of GABA A Rs labeled with quantum dots. GluRdependent dispersal of GABA A R clusters requires Ca 2+ influx via NMDA receptors (NMDARs) and activation of the phosphatase calcineurin. Moreover, the dispersal of GABA A R clusters and increased mobility of individual GABA A Rs are dependent on serine 327 within the intracellular loop of the GABA A R γ2 subunit. Thus, NMDAR signaling, via calcineurin and a key GABA A R phosphorylation site, controls the stability of synaptic GABA A Rs, with important implications for activitydependent control of synaptic inhibition and neuronal plasticity.ion channels | plasticity | trafficking | diffusion | calcineurin S ynaptic inhibition plays a critical role in regulating neuronal excitability and information processing in the brain. The number of GABA A receptors (GABA A Rs) in the surface membrane and at synaptic sites is an important determinant of inhibitory synapse strength (1), but the mechanisms that rapidly control synaptic GABA A R number and stability remain poorly understood. Activation of Ca 2+ -permeable ionotropic glutamate receptors (GluRs) during plasticity and in pathology can result in down-modulation of inhibitory synapse strength and GABA A R function (2-5) but the molecular and cellular mechanisms underlying GluR-dependent changes in the strength of GABAergic inhibition remain unclear.A major mechanism for modulating GABA A R activity is the direct phosphorylation of residues within the intracellular loops of GABA A R subunits, which can regulate synaptic inhibition, GABA A R channel kinetics, and trafficking (6-9). The rapid movement of neurotransmitter receptors (including GABA A Rs) (10-12) into and out of synapses has also recently emerged as an important mechanism for regulating synaptic strength (13). However, whether GABA A R phosphorylation can directly regulate the synaptic stability of GABA A Rs and their lateral diffusion and movement into and out of synapses is unknown.Here, by live cell imaging of surface GABA A R clusters with pHsensitive superecliptic pHluorin (SEP) and single GABA A Rs with quantum dots (QDs), we investigate the mechanisms that regulate activity-dependent control of the lateral diffusion, clustering, and stability of GABA A Rs at inhibitory synapses. We find that Ca 2+ entry through NMDA receptors (NMDARs) l...

Copy number variation (CNV) at the 15q11.2 region has been identified as a significant risk locus for neurological and neuropsychiatric conditions such as schizophrenia (SCZ) and autism spectrum disorder (ASD). However, the individual roles for genes at this locus in nervous system development, function and connectivity remain poorly understood. Haploinsufficiency of one gene in this region, Cyfip1, may provide a model for 15q11.2 CNV-associated neuropsychiatric phenotypes. Here we show that altering CYFIP1 expression levels in neurons both in vitro and in vivo influences dendritic complexity, spine morphology, spine actin dynamics and synaptic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor lateral diffusion. CYFIP1 is highly enriched at synapses and its overexpression in vitro leads to increased dendritic complexity. Neurons derived from Cyfip1 heterozygous animals on the other hand, possess reduced dendritic complexity, increased mobile F-actin and enhanced GluA2-containing AMPA receptor mobility at synapses. Interestingly, Cyfip1 overexpression or haploinsufficiency increased immature spine number, whereas activity-dependent changes in spine volume were occluded in Cyfip1 haploinsufficient neurons. In vivo, Cyfip1 heterozygous animals exhibited deficits in dendritic complexity as well as an altered ratio of immature-to-mature spines in hippocampal CA1 neurons. In summary, we provide evidence that dysregulation of CYFIP1 expression levels leads to pathological changes in CNS maturation and neuronal connectivity, both of which may contribute to the development of the neurological symptoms seen in ASD and SCZ.