Stimulating deep inside the brain: Noninvasive deep brain stimulation is an important goal in neuroscience and neuroengineering. Optogenetics normally requires the use of a blue laser inserted into the brain. Chen et al. used specialized nanoparticles that can upconvert near-infrared light from outside the brain into the local emission of blue light (see the Perspective by Feliu et al. ). They injected these nanoparticles into the ventral tegmental area of the mouse brain and activated channelrhodopsin expressed in dopaminergic neurons with near-infrared light generated outside the skull at a distance of several millimeters. This technique allowed distant near-infrared light to evoke fast increases in dopamine release. The method was also used successfully to evoke fear memories in the dentate gyrus during fear conditioning. Science , this issue p. 679 ; see also p. 633

Hippocampus receives dense serotonergic input specifically from raphe nuclei. However, what information is carried by this input and its impact on behavior has not been fully elucidated. Here we used in vivo two-photon imaging of activity of hippocampal median raphe projection fibers in behaving male and female mice and identified two distinct populations: one linked to reward delivery and the other to locomotion. Local optogenetic manipulation of these fibers confirmed a functional role for these projections in the modulation of reward-induced behavior. The diverse function of serotonergic inputs suggests a key role in integrating locomotion and reward information into the hippocampal CA1. SIGNIFICANCE STATEMENT Information constantly flows in the hippocampus, but only some of it is captured as a memory. One potential process that discriminates which information should be remembered is concomitance with reward. In this work, we report a neuromodulatory pathway, which delivers reward signal as well as locomotion signal to the hippocampal CA1. We found that the serotonergic system delivers heterogeneous input that may be integrated by the hippocampus to support its mnemonic functions. It is dynamically involved in regulating behavior through interaction with the hippocampus. Our results suggest that the serotonergic system interacts with the hippocampus in a dynamic and behaviorally specific manner to regulate reward-related information processing.

The Edinger-Westphal nucleus (EW) produces several neuropeptides, including urocortin 1 and cocaine-amphetamine-regulated transcript, which regulate feeding, energy balance, and anxiety. Additionally, the EW projects to feeding and anxiety-regulatory brain areas. The authors tested the effect of lesions of the EW on the consumption of food, water and flavored solutions, metabolic indices, and exploratory behavior on the elevated plus maze in male C57BL/6J mice. EW lesion significantly reduced basal and deprivation-induced food and fluid consumption compared with sham and placement controls, but it did not alter behavior on the elevated plus maze. EW lesion had no effect on indices of basal metabolic activity, including plasma glucose level and body temperature. These effects suggest that the peptidergic neurons of the EW regulate food consumption.