Sheila Nirenberg - US grants

Nirenberg, Shelia
IBN-9818445

The Neural Information and Coding Workshop (NIC) is a small (-60 people), intensive, three-day meeting devoted to the neural code. The objectives are two-fold: to bring together experimental and theoretical neuroscientists to share new ideas and results, and to discuss how new experimental and theoretical approaches can be combined to better understand neural coding.

Three kinds of participants are included: 1) experimentalists working on various aspects of this problem (although this group is growing rapidly, it is not yet a community, so relevant advances can go unnoticed without a forum for presentation); 2) experimentalists who are developing new technologies, such as optical imaging and multi-unit recording, that will be necessary for further progress; 3) theoreticians, since we do not currently have a unified frame work for thinking about the neural code.

DESCRIPTION (From the Applicant's Abstract): The goal of this project is to advance our understanding of how visual information is processed by the circuitry of the retina. Retinal circuitry is divided into two layers: the outer plexiform layer (OPL) and the inner plexiform layer (IPL). While much is known about the contribution of the OPL, that of the IPL has been difficult to ascertain. The aim of this project is to determine the contributions of specific neuronal cell populations in the IPL. This will be addressed using a technique for targeted cell class ablation. The method is to genetically engineer the cell class so that it will selectively label with a photoactivatable dye. Once labeled, the cells can be killed by photoablation. This method has been tested in vivo and in vitro on several different cell classes in the mouse retina and shown to be >90 percent effective with <2 percent non-specific cell death. With this method, we can test hypotheses about the actions of a specific cell population by ablating it from the circuitry and examining the effects on retinal output. Our research is divided into two parts. The first is to characterize the response properties of the retinal output neurons, the ganglion cells, in the mouse retina. The mouse will be used as our model system, because the method for ablating cells requires gene transfer, and the mouse is amenable to genetic manipulation. The response properties of the ganglion cells will be examined by presenting the isolated retina with light patterns generated on a computer monitor and recording ganglion cell spike trains with a multi-electrode array. The second part is to determine the roles of specific populations of interneurons in shaping these ganglion cell response properties. This project focuses on two interneuron populations, i) neuropeptide-Y-expressing amacrine cells, which are proposed to play a role in shaping the behavior of ganglion cells that respond to light offset (OFF cells), and ii) catecholaminergic interplexiform cells, which are proposed, based on studies in lower vertebrates, to act on horizontal cells and bipolar cells, and, through their action, to shape the center/surround organization of ganglion cell receptive fields. These hypotheses will be tested and other actions of these cell populations will be examined by ablating them from the retina and assessing changes in ganglion cell response properties. Anatomical and neurochemical properties of these populations will also be examined to gain information about how these cells mediate their effects. These studies will provide basic information about how retinal circuits process information and insight into mechanisms that underlie circuit malfunctions.

[unreadable] DESCRIPTION (provided by applicant): One (1) of the most difficult problems we face in neuroscience is understanding how neuronal networks process information. Understanding how a network operates depends on knowing what its component cell classes do-that is what their activity patterns are and how they relate to the activity patterns of other cell classes. Here we propose a new method for monitoring activity in neuronal systems. The method combines genetic and optical imaging techniques. Genetics allows specific cell classes to be targeted, and optical imaging allows the activity of the cells in each class to be monitored with high spatial and temporal resolution. The method is built around a marker protein, and the specific aims are as follows: Aims 1 and 2 focus on building compounds that react with the protein to produce activity-indicators, and Aim 3 focuses on testing the performance of the indicators (measuring their selectivity, dynamic range and kinetics). This tool has broad applications, both basic and applied, from monitoring cell-to-cell communication in the developing and mature nervous system to monitoring the actions (effectiveness and selectivity) of neuroactive drugs. [unreadable] [unreadable]

[unreadable] DESCRIPTION (provided by applicant): One of the most basic problems we face in systems neuroscience is understanding how information from the outside world is represented in the activity of populations of neurons. This proposal is directed toward this problem, and uses the retina - specifically, the output cells of the retina - as the model system. We focus on two key questions: 1) What code do the cells use to carry the information, and 2) what roles do the different classes of cells in the population play? To address these questions, we will use a combined electrophysiological and behavioral approach, with the rodent as the model species. Our specific aims are as follows: In Aim 1, we will test hypotheses about the codes used by the output cells. Specifically, we will decode their spike trains assuming different codes, measure the performance of the codes on visual discrimination tasks, and compare the performance to that of the animal. We will focus on a series of widely proposed codes, starting with a simple spike count code, and then advancing systematically through a set of more complex codes (a spike timing, a temporal correlation, and a cross-correlation code). We have set up an experimental protocol that allows us to obtain an upper bound on the performance of each code. With an upper bound, we can rigorously determine which codes are viable for the animal and which are not - that is, which codes the animal can be using and which codes must be ruled out. In Aim 2, we will test hypotheses about the contributions of the different classes of retinal output cells to the representation of visual scenes. We will do this by decoding the output cell spike trains with and without specific cell classes included. These studies will provide fundamental information about the strategies the nervous system uses to represent and process information. Since a substantial portion of the work involves mapping the input/output relationship of the retina, this research will also contribute to the development of algorithms for retinal prosthetics. [unreadable] [unreadable] [unreadable]