2 research outputs found
Silences, Spikes and Bursts: Three-Part Knot of the Neural Code
When a neuron breaks silence, it can emit action potentials in a number of
patterns. Some responses are so sudden and intense that electrophysiologists
felt the need to single them out, labeling action potentials emitted at a
particularly high frequency with a metonym -- bursts. Is there more to bursts
than a figure of speech? After all, sudden bouts of high-frequency firing are
expected to occur whenever inputs surge. The burst coding hypothesis advances
that the neural code has three syllables: silences, spikes and bursts. We
review evidence supporting this ternary code in terms of devoted mechanisms for
burst generation, synaptic transmission and synaptic plasticity. We also review
the learning and attention theories for which such a triad is beneficial.Comment: 15 pages, 4 figure
Simultaneous, Single-Particle Measurements of Size and Loading Give Insights into the Structure of Drug-Delivery Nanoparticles
Nanoparticles are a promising solution for delivery of a wide range of medicines and vaccines. Optimizing their design depends on being able to resolve, understand, and predict biophysical and therapeutic properties, as a function of design parameters. While existing tools have made great progress, gaps in understanding remain because of the inability to make detailed measurements of multiple correlated properties. Typically, an average measurement is made across a heterogeneous population, obscuring potentially important information. In this work, we develop and apply a method for characterizing nanoparticles with single-particle resolution. We use convex lens-induced confinement (CLiC) microscopy to isolate and quantify the diffusive trajectories and fluorescent intensities of individual nanoparticles trapped in microwells for long times. First, we benchmark detailed measurements of fluorescent polystyrene nanoparticles against prior data to validate our approach. Second, we apply our method to investigate the size and loading properties of lipid nanoparticle (LNP) vehicles containing silencing RNA (siRNA), as a function of lipid formulation, solution pH, and drug-loading. By taking a comprehensive look at the correlation between the intensity and size measurements, we gain insights into LNP structure and how the siRNA is distributed in the LNP. Beyond introducing an analytic for size and loading, this work allows for future studies of dynamics with single-particle resolution, such as LNP fusion and drug-release kinetics. The prime contribution of this work is to better understand the connections between microscopic and macroscopic properties of drug-delivery vehicles, enabling and accelerating their discovery and development