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On the anniversary of the Boyden et al. (2005) paper that introduced the use of channelrhodopsin in neurons, Nature Neuroscience asks selected members of the community to comment on the utility, impact and future of this important technique.

Cocaine chemogenetics in rats is a selective approach for countering drug reinforcement by clamping dopamine release in the presence of cocaine.

Cell-type-specific electrical activity manipulations and deep-brain imaging in mice of neuronal populations associated with homeostasis of nutrient or fluid intake reveals that learning is conditioned by a negative-valence signal from the hunger-mediating AGRP neurons and also from the thirst-mediating neurons in the subfornical organ.

In this paper, Atasoy and colleagues use a genetically-encoded synaptic marker for electron microscopy (GESEM) to probe long-range neuronal connectivity at the nanoscale level. The authors fused the horseradish peroxidase to the vesicle-associated membrane protein 2 (VAMP2) to label synaptic vesicles. Focusing on the mouse feeding system, they show that this new tool is suitable for connectomics analyses of genetically defined populations of neurons.

A metabolite called Lac-Phe is associated with exercise-induced ‘muscle burn’. This molecule has now been shown to reduce food intake after exercise in mice, racehorses and humans, and to trigger weight loss in obese mice.

A recent optogenetic method has been adapted to map long-range inputs onto various segments of the dendritic arborizations of cortical pyramidal neurons. Specific inputs tend to cluster in distinct domains within dendritic trees. Such spatial segregation of different axonal inputs within dendrites may strengthen coupling of coherent cell populations during neuronal information processing and learning.

Aponte et al. show that optogenetic activation of a population of hypothalamic neurons expressing agouti-related peptide (AGRP) is sufficient to evoke voracious feeding behavior in mice. This feeding was not dependent on suppressing the activity of anorexigenic pro-opiomelanocortin–expressing neurons, suggesting that AGRP neurons directly engage feeding circuits.

A specialist neuron uses an intriguing process to help control the body's response to hunger. A lipid pathway involving the breakdown of cellular components regulates the expression of a neuropeptide that affects feeding and body weight.

This study maps the single-axon projections of 7,180 hypothalamic peptidergic neurons in male mice and uncovers extensive collateralization, topographic target innervation and modular intra-hypothalamic organization.

Using optogenetic and pharmacogenetic techniques, the authors find that AGRP neurons suppress oxytocin-releasing neurons, which is a critical interaction for evoked feeding; thus they identify a circuit potentially involved in regulating hunger state.

The authors use optical activation and cell type–specific pharmacogenetic silencing in vitro to show that dendritic inhibition critically regulates input-output transformations in mouse hippocampal CA1 pyramidal cells. Dendrite-targeting interneurons are themselves modulated by interneurons targeting pyramidal cell somata.

GABA-expressing neurons in the arcuate nucleus of the hypothalamus regulate obesity in mice. A recent study indicates the importance of unexamined cell types.

Optogenetic suppression of layer 4 in the sensory cortex reveals a surprising role for its activity in the cortical microcircuit: layer 4 suppresses the main cortical output layer—layer 5—through a direct translaminar inhibitory circuit. This translaminar inhibition sharpens spatial representations in the somatosensory cortex.

Eiselt et al. report conditions under which mice confuse thirst for hunger, similar to some human decisions that lead to over-eating. Evaluation of physiological need state requires consuming food or water and depends on the prefrontal cortex.