To better understand how organisms make decisions on the basis of temporally varying multi-sensory input, we identified computations made by Drosophila larvae responding to visual and optogenetically induced fictive olfactory stimuli. We modeled the larva's navigational decision to initiate turns as the output of a Linear-Nonlinear-Poisson cascade. We used reverse-correlation to fit parameters to this model; the parameterized model predicted larvae's responses to novel stimulus patterns. For multi-modal inputs, we found that larvae linearly combine olfactory and visual signals upstream of the decision to turn. We verified this prediction by measuring larvae's responses to coordinated changes in odor and light. We studied other navigational decisions and found that larvae integrated odor and light according to the same rule in all cases. These results suggest that photo-taxis and odor-taxis are mediated by a shared computational pathway.DOI: http://dx.doi.org/10.7554/eLife.06229.001

Nanopores can probe the structure of biopolymers in solution; however, diffusion makes it difficult to study the same molecule for extended periods. Here we report devices that entropically trap single DNA molecules in a 6.2-femtolitre cage near a solid-state nanopore. We electrophoretically inject DNA molecules into the cage through the nanopore, pause for preset times and then drive the DNA back out through the nanopore. The saturating recapture time and high recapture probability after long pauses, their agreement with a convection-diffusion model and the observation of trapped DNA under fluorescence microscopy all confirm that the cage stably traps DNA. Meanwhile, the cages have 200 nm openings that make them permeable to small molecules, like the restriction endonuclease we use to sequence-specifically cut trapped DNA into fragments whose number and sizes are analysed upon exiting through the nanopore. Entropic cages thus serve as reactors for chemically modifying single DNA molecules.

Highlights d Three-dimensional morphologies of proprioceptive dendrites during movement are described d Drosophila larval proprioceptive neurons are tuned to direction of locomotion d ddaE responds to forward locomotion while ddaD responds to backward locomotion d Tmc channels are required for sensing movement direction

SUMMARY Optical recordings of neural activity in behaving animals can reveal the neural correlates of decision making, but brain motion, which often accompanies behavior, compromises these measurements. Two-photon point-scanning microscopy is especially sensitive to motion artifacts, and two-photon recording of activity has required rigid coupling between the brain and microscope. We developed a two-photon tracking microscope with extremely low-latency (360 μs) feedback implemented in hardware. This microscope can maintain continuous focus on neurons moving with velocities of 3 mm/s and accelerations of 1 m/s2 both in-plane and axially. We recorded calcium dynamics of motor neurons and inter-neurons in unrestrained freely behaving fruit fly larvae, correlating neural activity with stimulus presentations and behavioral outputs, and we measured light-induced depolarization of a visual interneuron in a moving animal using a genetically encoded voltage indicator. Our technique can be extended to stabilize recordings in a variety of moving substrates.