Single Neuron Computation:Dendritic Information Processing with Studied with High-Speed Laser-Scanning Methods.

Baylor College Of Medicine, Houston TX

Investigators

Abstract

The receptive parts of most neurons (nerve cells) in the brain are the branches called dendrites. These dendrites are covered with spiny structures, which are part of the functional contacts between nerve cells called synapses. These spines receive signals from the synaptic terminals of other neurons. Neurotransmitters are the biochemical compounds that carry a signal across the small gap between the pre- and the post-synaptic sides, and generate the electrochemical membrane response in the post-synaptic cell. Dendritic size, complexity, and accessibility, together with the hundreds or thousands of synaptic contacts on a single cell, make it technically difficult to study the local dynamic mechanisms underlying this synaptic signaling at this microscopic scale. It is very difficult to elicit a physiological multi-site stimulation pattern and to perform multi-site recordings of the membrane potential, especially to measure local synaptic potentials concurrently at different sites in the same cell. This project uses novel optical methods in addition to the powerful 'patch-clamp' electronic technique for whole-cell physiological recordings. An optical workstation has been developed that uses a pulsed ultraviolet (UV) laser beam with a novel acoustico-optic control for microsecond timing of the position of a spot in the micrometer size range, in connection with a biochemical compound that acts as a 'cage' around neurotransmitter molecules to keep them 'invisible' for their receptors. When caged molecules are hit with the laser beam, the light energy immediately breaks the cage (photolysis) and free transmitter can act on the synapse. High-resolution differential-interference-contrast (DIC) microscopy of neurons in culture, with the pulsed random-access laser-scanning photolysis, and a new technique of laser-scanning fluorescence microscopy of voltage-sensitive dye bound to the cell membranes are combined to allow a new level of computer-controlled, non-invasive, high-resolution stimulation and recording. This powerful technology is used to examine the functional role of dendritic structural details, to characterize spatio-temporal interactions among dendritic synapses, the computational functions that can be assigned to dendrites in integrating signals, and the effects of prior activity on dendritic behavior. Results will be important for understanding the fundamental role of dendrites for cellular information processing, and for refining computational compartmental models of nerve cells. The impact of the technology also will extend beyond cellular neuroscience to cellular biology. In addition, exceptional cross-disciplinary opportunities will be provided for postdoctoral and graduate training.