GABAergic control of retinal ganglion cell dendritic development.

Developing GABAergic neurons mature long before excitatory neurons, and early GABA(A) activity exerts important paracrine effects while neurons extend dendrites and axons and they establish neural connections. One of the unique features of early GABA(A) activity is that it induces membrane depolarization and Ca(2+) influx and it shifts to inhibition when networks mature. Although it has been demonstrated in several systems that early GABA(A) signaling plays a fundamental role in guiding neurite outgrowth, it has never been investigated in the retina. Here we show that chronic GABAergic activity is required for the stabilization and maintenance of newly formed dendritic branches in developing turtle retinal ganglion cells (RGCs) in ovo. Blocking GABA(A) receptors with bicuculline or inhibiting GABA synthesis with l-allylglycine have contrasting effects on dendritic growth and branching in biocytin-labeled RGCs. Dendritic arbor reconstruction shows that bicuculline induces dendritic branch loss without global change in the extent of dendritic fields while l-allylglycine causes the entire tree to shrink. At the same time, multielectrode array recordings and Ca(2+) imaging show that l-allylglycine has similar effects to bicuculline (Leitch et al., 2005) on overall network excitability, preventing the disappearance of immature retinal waves of activity and the GABAergic polarity shift. This study demonstrates for the first time that GABA plays an important role in vivo in stabilizing developing dendrites into mature arbors in the retina. However, the way GABA influences dendritic growth appears to be driven by complex mechanisms that cannot be explained solely on the basis of overall network activity levels.

Development of retinal ganglion cell structure and function.

In this review, we summarize the main stages of structural and functional development of retinal ganglion cells (RGCs). We first consider the various mechanisms that are involved in restructuring of dendritic trees. To date, many mechanisms have been implicated including target-dependent factors, interactions from neighboring RGCs, and afferent signaling. We also review recent evidence showing how rapidly such dendritic remodeling might occur, along with the intracellular signaling pathways underlying these rearrangements. Concurrent with such structural changes, the functional responses of RGCs also alter during maturation, from sub-threshold firing to reliable spiking patterns. Here we consider the development of intrinsic membrane properties and how they might contribute to the spontaneous firing patterns observed before the onset of vision. We then review the mechanisms by which this spontaneous activity becomes correlated across neighboring RGCs to form waves of activity. Finally, the relative importance of spontaneous versus light-evoked activity is discussed in relation to the emergence of mature receptive field properties.

Lateral cell movement driven by dendritic interactions is sufficient to form retinal mosaics.

The formation of retinal mosaics is thought to involve lateral movement of retinal cells from their clonal column of origin. The forces underlying this lateral cell movement are currently unknown. We have used a model of neurite outgrowth combined with cell movement to investigate the hypothesis that lateral cell movement is guided by dendritic interactions. We have assumed that cells repel each other in proportion to the degree of dendritic overlap between neighbouring cells. Our results first show that small cell movements are sufficient to transform random cell distributions into regular mosaics, and that all cells within the population move. When dendritic fields are allowed to grow, the model produces regular mosaics across all cell densities tested. We also find that the model can produce constant coverage of visual space over varying cell densities. However, if dendritic field sizes are fixed, mosaic regularity is proportional to the cell density and dendritic field size. Our model suggests that dendritic mechanisms may therefore provide sufficient information for rearrangement of cells into regular mosaics. We conclude by mentioning possible future experiments that might suggest whether dendritic interactions are adaptive or fixed during mosaic formation.

Differential effects of acetylcholine and glutamate blockade on the spatiotemporal dynamics of retinal waves.

In the immature vertebrate retina, neighboring ganglion cells express spontaneous bursting activity (SBA), resulting in propagating waves. Previous studies suggest that the spontaneous bursting activity, asynchronous between the two eyes, controls the refinement of retinal ganglion cell projections to central visual targets. To understand how the patterns encoded within the waves contribute to the refinement of connections in the visual system, it is necessary to understand how wave propagation is regulated. We have used video-rate calcium imaging of spontaneous bursting activity in chick embryonic retinal ganglion cells to show how glutamatergic and cholinergic connections, two major excitatory synaptic drives involved in spontaneous bursting activity, contribute differentially to the spatiotemporal patterning of the waves. During partial blockade of cholinergic connections, cellular recruitment declines, leading to spatially more restricted waves. The velocity of wave propagation decreases during partial blockade of glutamatergic connections, but cellular recruitment remains substantially higher than during cholinergic blockade, thereby altering correlations in the activity of neighboring and distant ganglion cells. These findings show that cholinergic and glutamatergic connections exert different influences on the spatial and temporal properties of the waves, raising the possibility that they may play distinct roles during visual development.

The role of retinal waves and synaptic normalization in retinogeniculate development.

The prenatal development of the cat retinogeniculate pathway is thought to involve activity-dependent mechanisms driven by spontaneous waves of retinal activity. The role of these waves upon the segregation of the dorsal lateral geniculate nucleus (LGN) into two eye-specific layers and the development of retinotopic mappings have previously been investigated in a computer model. Using this model, we examine three aspects of retinogeniculate development. First, the mapping of visual space across the whole network into projection columns is shown to be similar to the mapping found in the cat. Second, the simplicity of the model allows us to explore how different forms of synaptic normalization affect development. In comparison to most previous models of ocular dominance, we find that subtractive postsynaptic normalization is redundant and divisive presynaptic normalization is sufficient for normal development. Third, the model predicts that the more often one eye generates waves relative to the other eye, the more LGN units will monocularly respond to the more active eye. In the limit when one eye does not generate any waves, that eye totally disconnects from the LGN allowing the non-deprived eye to innervate all of the LGN. Thus, as well as accounting for normal retinogeniculate development, the model also predicts development under abnormal conditions which can be experimentally tested.

An introduction to natural computation.

by Dana H. Ballard, MIT Press, 1997. $45.00 (xxii+307 pages) ISBN 0 262 02420 9.

Automated feature extraction for the classification of human in vivo 13C NMR spectra using statistical pattern recognition and wavelets.

If magnetic resonance spectroscopy (MRS) is to become a useful tool in clinical medicine, it will be necessary to find reliable methods for analyzing and classifying MRS data. Automated methods are desirable because they can remove user bias and can deal with large amounts of data, allowing the use of all the available information. In this study, techniques for automatically extracting features for the classification of MRS in vivo data are investigated. Among the techniques used were wavelets, principal component analysis, and linear discriminant function analysis. These techniques were tested on a set of 75 in vivo 13C spectra of human adipose tissue from subjects from three different dietary groups (vegan, vegetarian, and omnivore). It was found that it was possible to assign automatically 94% of the vegans and omnivores to their correct dietary groups, without the need for explicit identification or measurement of peaks.