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S Nirenberg

Publications and source records attributed to S Nirenberg.

9 recordsLinked to original sources

Retinal ganglion cells act largely as independent encoders.

Correlated firing among neurons is widespread in the visual system. Neighbouring neurons, in areas from retina to cortex, tend to fire together more often than would be expected by chance. The importance of this correlated firing for encoding visual information is unclear and controversial. Here we examine its importance in the retina. We present the retina with natural stimuli and record the responses of its output cells, the ganglion cells. We then use information theoretic techniques to measure the amount of information about the stimuli that can be obtained from the cells under two conditions: when their correlated firing is taken into account, and when their correlated firing is ignored. We find that more than 90% of the information about the stimuli can be obtained from the cells when their correlated firing is ignored. This indicates that ganglion cells act largely independently to encode information, which greatly simplifies the problem of decoding their activity.

Animals↗

Characterization of neuropeptide Y-expressing cells in the mouse retina using immunohistochemical and transgenic techniques.

The amacrine cells of the retina are a complex family of interneurons. They are made up of numerous subgroups, each with different morphologic and/or biochemical properties and each presumably serving a different function. In this study, we characterized one subgroup, defined by its expression of a peptide, neuropeptide Y (NPY). The cells were identified using antibodies to NPY and characterized using a transgenic mouse line that expressed the reporter enzyme, beta-galactosidase, in the NPY-immunoreactive (NPY-IR) cells. We found that NPY-IR cells were present in two layers, the inner nuclear layer (INL) and the ganglion cell layer (GCL). The cells in both layers were densely distributed, with those in the INL having a mean density of 1452 +/- 65 cells/mm(2), and those in the GCL having a mean density of 644 +/- 41 cells/mm(2). The cells in the INL extended their processes in the sublamina of the inner plexiform layer (IPL) closest to the INL/IPL border, the presumptive OFF sublamina, and the cells in the GCL extended their processes in the sublamina near the GCL/IPL border, the presumptive ON sublamina. Both populations of cells were immunoreactive to a GABA transporter and, thus, likely GABAergic. The high density of these cells suggests that they play a prominent role in IPL processing. The location of their processes suggests that one population acts in the pathway that mediates OFF responses, and the other in the pathway that mediates ON responses, and their expression of a GABA marker indicates that their actions are likely inhibitory.

Animals↗

Intrinsic dynamics in neuronal networks. I. Theory.

Many networks in the mammalian nervous system remain active in the absence of stimuli. This activity falls into two main patterns: steady firing at low rates and rhythmic bursting. How are these firing patterns generated? Specifically, how do dynamic interactions between excitatory and inhibitory neurons produce these firing patterns, and how do networks switch from one firing pattern to the other? We investigated these questions theoretically by examining the intrinsic dynamics of large networks of neurons. Using both a semianalytic model based on mean firing rate dynamics and simulations with large neuronal networks, we found that the dynamics, and thus the firing patterns, are controlled largely by one parameter, the fraction of endogenously active cells. When no endogenously active cells are present, networks are either silent or fire at a high rate; as the number of endogenously active cells increases, there is a transition to bursting; and, with a further increase, there is a second transition to steady firing at a low rate. A secondary role is played by network connectivity, which determines whether activity occurs at a constant mean firing rate or oscillates around that mean. These conclusions require only conventional assumptions: excitatory input to a neuron increases its firing rate, inhibitory input decreases it, and neurons exhibit spike-frequency adaptation. These conclusions also lead to two experimentally testable predictions: 1) isolated networks that fire at low rates must contain endogenously active cells and 2) a reduction in the fraction of endogenously active cells in such networks must lead to bursting.

Action Potentials↗

Intrinsic dynamics in neuronal networks. II. experiment.

Neurons in many regions of the mammalian CNS remain active in the absence of stimuli. This activity falls into two main patterns: steady firing at low rates and rhythmic bursting. How these firing patterns are maintained in the presence of powerful recurrent excitation, and how networks switch between them, is not well understood. In the previous paper, we addressed these issues theoretically; in this paper we address them experimentally. We found in both studies that a key parameter in controlling firing patterns is the fraction of endogenously active cells. The theoretical analysis indicated that steady firing rates are possible only when the fraction of endogenously active cells is above some threshold, that there is a transition to bursting when it falls below that threshold, and that networks becomes silent when the fraction drops to zero. Experimentally, we found that all steadily firing cultures contain endogenously active cells, and that reducing the fraction of such cells in steadily firing cultures causes a transition to bursting. The latter finding implies indirectly that the elimination of endogenously active cells would cause a permanent drop to zero firing rate. The experiments described here thus corroborate the theoretical analysis.

Action Potentials↗

A novel signaling pathway from rod photoreceptors to ganglion cells in mammalian retina.

Current understanding suggests that mammalian rod photoreceptors connect only to an ON-type bipolar cell. This rod-specific bipolar cell excites the All amacrine cell, which makes connections to cone-specific bipolar cells of both ON and OFF type; these, in turn, synapse with ganglion cells. Recent work on rabbit retina has shown that rod signals can also reach ganglion cells without passing through the rod bipolar cell. This route was thought to be provided by electrical gap junctions, through which rods signal directly to cones and thence to cone bipolar cells. Here, we show that the mouse retina also provides a rod pathway bypassing the rod bipolar cell, suggesting that this is a common feature in mammals. However, this alternative pathway does not require cone photoreceptors; it is perfectly intact in a transgenic mouse whose retina lacks cones. Instead, the results can be explained if rods connect directly to OFF bipolar cells.

Aminobutyrates↗

Population coding in the retina.

Recent advances in multi-electrode recording have brought us closer to understanding how visual information is encoded by populations of retinal ganglion cells. By monitoring the visual responses of many ganglion cells at once, it is now possible to examine how ganglion cells act together to encode a visual scene.

Animals↗

The light response of retinal ganglion cells is truncated by a displaced amacrine circuit.

The vertebrate retina contains ganglion cells that appear to be specialized for detecting temporal changes. The characteristic response of these cells is a transient burst of action potentials when a stationary image is presented or removed, and often a strong discharge to moving images. These transient and motion-sensitive responses are thought to result from processing in the inner retina that involves amacrine cells, but the critical interactions have been difficult to reveal. Here, we used a cell-ablation technique to remove a subpopulation of amacrine cells from the mouse retina. Their ablation changed transient ganglion cell responses into prolonged discharges. This suggests that transient responses are generated, at least in part, by a truncation of sustained excitatory input to the ganglion cells and that the ablated amacrine cells are critical for this process.

Animals↗

Targeted ablation of diverse cell classes in the nervous system in vivo.

The study of both the function and development of complex neural systems would be greatly facilitated by a means for systematically blocking intercell communication. One way of preventing cells from signaling each other is to remove them from the system by ablation. Here we present a general technique for visualizing and ablating selected cell classes in vivo. The cells of interest are genetically engineered so that they can be selectively labeled with a photoactivatable dye and visualized in living preparations; the dye-labeled cells can then be photoablated. This approach is applicable to a broad range of cell types, in organisms amenable to gene transfer, and permits ablations to be performed at different developmental stages or in the adult. We demonstrate the use of this technique on several cell types in the mouse retina and cerebral cortex, and in the zebrafish embryo.

Affinity Labels↗