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This paper describes a single-vector strategy for flexible intersectional expression of genetically encoded reporters and tools in precisely defined cell types in the mouse.

Ion channels driven by light have provided electrophysiologists with unprecedented control over the activity state of neurons; here Deisseroth and colleagues introduce new molecules that offer a similar level of control over signalling pathways to biochemists. Opsin/GPCR chimaeras were engineered, enabling the authors to modulate G-protein activity via light, which in turn could influence neuronal firing; activating these molecules expressed in vivo could drive conditioned place preference in behaving mice

Blood oxygenation level-dependent (BOLD) signals are the basis for much of the work on which regions of the human brain are active during particular tasks or behaviours, but there is controversy over their source and interpretation. Here a combination of optogenetics and BOLD signal monitoring shows that specific excitatory neurons within a mixed population are sufficient to produce positive BOLD signals, and could be used to map connections.

The amygdala, a brain region important for learning fearful memories, is thought to have a role in generalized anxiety, but the critical subregions and connections are unknown. This paper shows that optogenetic stimulation of basolateral amygdala (BLA) terminals in the central nucleus of the amygdala of rats with channelrhodopsin has an anxiolytic effect, whereas inhibition of the same projection with eNpHR3.0 increases anxiety related behaviours. These effects were not observed with direct optogenetic control of BLA somata themselves, indicating that selective activation of certain connections can have different effects.

The crystal structure of anion channelrhodopsin-1 (ACR1) from the algae Guillardia theta provides insights into the basis of anion conductance.

The authors establish a connection between functional subtypes and genetic subtypes of dopamine neurons in mice and demonstrate that molecular expression patterns can serve as a common framework to dissect dopaminergic functions.

Crystal structures and molecular simulations of the designed anion-conducting channelrhodopsin iC++ provide molecular insights that enable structure-based design of channelrhodopsins with desirable properties for use as optogenetic tools.

A combination of optogenetic, electrophysiological and neuroanatomical tracing methods defines midbrain periaqueductal grey circuits for specific defensive behaviours.

The sensory thalamus gets cortical input that drives feed-forward inhibition of thalamocortical cells (TC) via reticular thalamic nucleus (nRT) neurons during oscillations. Using genetically modified mice, the authors find that oscillations can still be initiated by cortical inputs via a cortico-TC-nRT-TC pathway when there is a specific reduction in the strength of the cortico-nRT-TC pathway.

In this Analysis, the authors directly experimentally compare microbial opsins used for the control of neural activity. They extract essential principles and key parameters that can help end users with the design and interpretation of optogenetic experiments and guide tool developers in the characterization of future tools.

The authors show that PKC-δ-expressing neurons in the central amygdala, are essential for synaptic plasticity underlying learning in the lateral amygdala, as they convey information about unconditioned stimulus to the lateral amygdala as a teaching signal.