Cell-type-specific binocular vision guides predation in mice.

Predators use vision to hunt, and hunting success is one of evolution's main selection pressures. However, how viewing strategies and visual systems are adapted to predation is unclear. Tracking predator-prey interactions of mice and crickets in 3D, we find that mice trace crickets with their binocular visual fields and that monocular mice are poor hunters. Mammalian binocular vision requires ipsi- and contralateral projections of retinal ganglion cells (RGCs) to the brain. Large-scale single-cell recordings and morphological reconstructions reveal that only a small subset (9 of 40+) of RGC types in the ventrotemporal mouse retina innervate ipsilateral brain areas (ipsi-RGCs). Selective ablation of ipsi-RGCs (<2% of RGCs) in the adult retina drastically reduces the hunting success of mice. Stimuli based on ethological observations indicate that five ipsi-RGC types reliably signal prey. Thus, viewing strategies align with a spatially restricted and cell-type-specific set of ipsi-RGCs that supports binocular vision to guide predation.

A Pixel-Encoder Retinal Ganglion Cell with Spatially Offset Excitatory and Inhibitory Receptive Fields.

The spike trains of retinal ganglion cells (RGCs) are the only source of visual information to the brain. Here, we genetically identify an RGC type in mice that functions as a pixel encoder and increases firing to light increments (PixON-RGC). PixON-RGCs have medium-sized dendritic arbors and non-canonical center-surround receptive fields. From their receptive field center, PixON-RGCs receive only excitatory input, which encodes contrast and spatial information linearly. From their receptive field surround, PixON-RGCs receive only inhibitory input, which is temporally matched to the excitatory center input. As a result, the firing rate of PixON-RGCs linearly encodes local image contrast. Spatially offset (i.e., truly lateral) inhibition of PixON-RGCs arises from spiking GABAergic amacrine cells. The receptive field organization of PixON-RGCs is independent of stimulus wavelength (i.e., achromatic). PixON-RGCs project predominantly to the dorsal lateral geniculate nucleus (dLGN) of the thalamus and likely contribute to visual perception.

Turtle Flexion Reflex Motor Patterns Show Windup, Mediated Partly by L-type Calcium Channels.

Windup is a form of multisecond temporal summation in which identical stimuli, delivered seconds apart, trigger increasingly strong neuronal responses. L-type Ca2+ channels have been shown to play an important role in the production of windup of spinal cord neuronal responses, initially in studies of turtle spinal cord and later in studies of mammalian spinal cord. L-type Ca2+ channels have also been shown to contribute to windup of limb withdrawal reflex (flexion reflex) in rats, but flexion reflex windup has not previously been described in turtles and its cellular mechanisms have not been studied. We studied windup of flexion reflex motor patterns, evoked with weak mechanical and electrical stimulation of the dorsal hindlimb foot skin and assessed via a hip flexor (HF) nerve recording, in spinal cord-transected and immobilized turtles in vivo. We found that an L-type Ca2+ channel antagonist, nifedipine, applied at concentrations of 50 µM or 100 µM to the hindlimb enlargement spinal cord, significantly reduced windup of flexion reflex motor patterns, while lower concentrations of nifedipine had no such effect. Nifedipine similarly reduced the amplitude of an individual flexion reflex motor pattern evoked by a stronger mechanical stimulus, in a dose-dependent manner, suggesting that L-type Ca2+ channels contribute to each flexion reflex as well as to multisecond summation of flexion reflex responses in turtles. We also found that we could elicit flexion reflex windup consistently using a 4-g von Frey filament, which is not usually considered a nociceptive stimulus. Thus, it may be that windup can be evoked by a wide range of tactile stimuli and that L-type calcium channels contribute to multisecond temporal summation of diverse tactile stimuli across vertebrates.

Local processing in neurites of VGluT3-expressing amacrine cells differentially organizes visual information.

Neurons receive synaptic inputs on extensive neurite arbors. How information is organized across arbors and how local processing in neurites contributes to circuit function is mostly unknown. Here, we used two-photon Ca2+ imaging to study visual processing in VGluT3-expressing amacrine cells (VG3-ACs) in the mouse retina. Contrast preferences (ON vs. OFF) varied across VG3-AC arbors depending on the laminar position of neurites, with ON responses preferring larger stimuli than OFF responses. Although arbors of neighboring cells overlap extensively, imaging population activity revealed continuous topographic maps of visual space in the VG3-AC plexus. All VG3-AC neurites responded strongly to object motion, but remained silent during global image motion. Thus, VG3-AC arbors limit vertical and lateral integration of contrast and location information, respectively. We propose that this local processing enables the dense VG3-AC plexus to contribute precise object motion signals to diverse targets without distorting target-specific contrast preferences and spatial receptive fields.

Phospholipid-stabilized nanoparticles of cyclosporine A by rapid expansion from supercritical to aqueous solution.

The purpose of this research was to form stable suspensions of submicron particles of cyclosporine A, a water-insoluble drug, by rapid expansion from supercritical to aqueous solution (RESAS). A solution of cyclosporine A in CO2 was expanded into an aqueous solution containing phospholipid vesicles mixed with nonionic surfactants to provide stabilization against particle growth resulting from collisions in the expanding jet. The products were evaluated by measuring drug loading with high performance liquid chromatography (HPLC), particle sizing by dynamic light scattering (DLS), and particle morphology by transmission electron microscopy (TEM) and x-ray diffraction. The ability of the surfactant molecules to orient at the surface of the particles and provide steric stabilization could be manipulated by changing process variables including temperature and suspension concentration. Suspensions with high payloads (up to 54 mg/mL) could be achieved with a mean diameter of 500 nm and particle size distribution ranging from 40 to 920 nm. This size range is several hundred nanometers smaller than that produced by RESAS for particles stabilized by Tween 80 alone. The high drug payloads (approximately 10 times greater than the equilibrium solubility), the small particle sizes, and the long-term stability make this process attractive for development.