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Michael B Orger

Publications and source records attributed to Michael B Orger.

4 recordsLinked to original sources
PubMed2007

Vesicular glutamate transport at a central synapse limits the acuity of visual perception in zebrafish.

The neural circuitry that constrains visual acuity in the CNS has not been experimentally identified. We show here that zebrafish blumenkohl (blu) mutants are impaired in resolving rapid movements and fine spatial detail. The blu gene encodes a vesicular glutamate transporter expressed by retinal ganglion cells. Mutant retinotectal synapses release less glutamate, per vesicle and per terminal, and fatigue more quickly than wild-type in response to high-frequency stimulation. In addition, mutant axons arborize more extensively, thus increasing the number of synaptic terminals and effectively normalizing the combined input to postsynaptic cells in the tectum. This presumably homeostatic response results in larger receptive fields of tectal cells and a degradation of the retinotopic map. As predicted, mutants have a selective deficit in the capture of small prey objects, a behavior dependent on the tectum. Our studies successfully link the disruption of a synaptic protein to complex changes in neural circuitry and behavior.

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PubMed2005

Forward genetic analysis of visual behavior in zebrafish.

The visual system converts the distribution and wavelengths of photons entering the eye into patterns of neuronal activity, which then drive motor and endocrine behavioral responses. The gene products important for visual processing by a living and behaving vertebrate animal have not been identified in an unbiased fashion. Likewise, the genes that affect development of the nervous system to shape visual function later in life are largely unknown. Here we have set out to close this gap in our understanding by using a forward genetic approach in zebrafish. Moving stimuli evoke two innate reflexes in zebrafish larvae, the optomotor and the optokinetic response, providing two rapid and quantitative tests to assess visual function in wild-type (WT) and mutant animals. These behavioral assays were used in a high-throughput screen, encompassing over half a million fish. In almost 2,000 F2 families mutagenized with ethylnitrosourea, we discovered 53 recessive mutations in 41 genes. These new mutations have generated a broad spectrum of phenotypes, which vary in specificity and severity, but can be placed into only a handful of classes. Developmental phenotypes include complete absence or abnormal morphogenesis of photoreceptors, and deficits in ganglion cell differentiation or axon targeting. Other mutations evidently leave neuronal circuits intact, but disrupt phototransduction, light adaptation, or behavior-specific responses. Almost all of the mutants are morphologically indistinguishable from WT, and many survive to adulthood. Genetic linkage mapping and initial molecular analyses show that our approach was effective in identifying genes with functions specific to the visual system. This collection of zebrafish behavioral mutants provides a novel resource for the study of normal vision and its genetic disorders.

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PubMedDate not supplied

Channeling of red and green cone inputs to the zebrafish optomotor response.

Visual systems break scenes down into individual features, processed in distinct channels, and then selectively recombine those features according to the demands of particular behavioral tasks. In primates, for example, there are distinct pathways for motion and form processing. While form vision utilizes color information, motion pathways receive input from only a subset of cone photoreceptors and are generally colorblind. To explore the link between early channeling of visual information and behavioral output across vertebrate species, we measured the chromatic inputs to the optomotor response of larval zebrafish. Using cone-isolating gratings, we found that there is a strong input from both red and green cones but not short-wavelength cones, which nevertheless do contribute to another behavior, phototaxis. Using a motion-nulling method, we measured precisely the input strength of gratings that stimulated cones in combination. The fish do not respond to gratings that stimulate different cone types out of phase, but have an enhanced response when the cones are stimulated together. This shows that red and green cone signals are pooled at a stage before motion detection. Since the two cone inputs are combined into a single 'luminance' channel, the response to sinusoidal gratings is colorblind. However, we also find that the relative contributions of the two cones at isoluminance varies with spatial frequency. Therefore, natural stimuli, which contain a mixture of spatial frequencies, are likely to be visible regardless of their chromatic composition.

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