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

Improved spy tactics for single cells: Bioluminescence imaging is a tremendous asset to medical research, providing a way to monitor living cells noninvasively within their natural environments. Advances in imaging methods allow researchers to measure tumor growth, visualize developmental processes, and track cell-cell interactions. Yet technical limitations exist, and it is difficult to image deep tissues or detect low cell numbers in vivo. Iwano et al. designed a bioluminescence imaging system that produces brighter emission by up to a factor of 1000 compared with conventional technology (see the Perspective by Nasu and Campbell). Individual tumor cells were successfully visualized in the lungs of mice. Small numbers of striatal neurons were detected in the brains of naturally behaving marmosets. The ability of the substrate to cross the blood-brain barrier should provide important opportunities for neuroscience research. Science , this issue p. 935 ; see also p. 868

Support for the memory index theory: The link between contextual memory representations and locations or routes represented by hippocampal place cells during exploration remains unknown. Tanaka et al. examined spatial firing properties of neurons in hippocampal area CA1 on the basis of whether they had recently expressed the immediate-early activity-induced gene c-Fos in response to a novel context. The c-Fos–positive neurons displayed a more on-off firing pattern than the c-Fos–negative cells during context discrimination. In a contextual recognition paradigm, these results support the index theory of hippocampal function over a cognitive mapping theory. Science , this issue p. 392

Overcoming aversive emotional memories requires neural systems that detect when fear responses are no longer appropriate so that they can be extinguished. The midbrain ventral tegmental area (VTA) dopamine system has been implicated in reward and more broadly in signaling when a better-than-expected outcome has occurred. This suggests that it may be important in guiding fear to safety transitions. We report that when an expected aversive outcome does not occur, activity in midbrain dopamine neurons is necessary to extinguish behavioral fear responses and engage molecular signaling events in extinction learning circuits. Furthermore, a specific dopamine projection to the nucleus accumbens medial shell is partially responsible for this effect. In contrast, a separate dopamine projection to the medial prefrontal cortex opposes extinction learning. This demonstrates a novel function for the canonical VTA-dopamine reward system and reveals opposing behavioral roles for different dopamine neuron projections in fear extinction learning.

Where and when of memory consolidation: Episodic memory is initially encoded in the hippocampus and later transferred to other brain regions for long-term storage. Synaptic plasticity underlies learning and plays a critical role in memory consolidation. However, it remains largely unknown where and when synaptic plasticity occurs and how it shapes the neuronal representation. Goto et al . developed a new tool for controlling early structural long-term potentiation (sLTP). By selectively manipulating sLTP, the authors showed that the local circuitry in hippocampal area CA1 is required for memory formation shortly after the encoding event. The local circuitry is also important for offline memory consolidation within 24 hours. The anterior cingulate cortex, another brain region directly connected with area CA1, is crucial for memory consolidation during sleep on the second night. —PRS