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Ethan Gahtan

Publications and source records attributed to Ethan Gahtan.

8 recordsLinked to original sources
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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PubMed2005

Visual prey capture in larval zebrafish is controlled by identified reticulospinal neurons downstream of the tectum.

Many vertebrates are efficient hunters and recognize their prey by innate neural mechanisms. During prey capture, the internal representation of the prey's location must be constantly updated and made available to premotor neurons that convey the information to spinal motor circuits. We studied the neural substrate of this specialized visuomotor system using high-speed video recordings of larval zebrafish and laser ablations of candidate brain structures. Seven-day-old zebrafish oriented toward, chased, and consumed paramecia with high accuracy. Lesions of the retinotectal neuropil primarily abolished orienting movements toward the prey. Wild-type fish tested in darkness, as well as blind mutants, were impaired similarly to tectum-ablated animals, suggesting that prey capture is mainly visually mediated. To trace the pathway further, we examined the role of two pairs of identified reticulospinal neurons, MeLc and MeLr, located in the nucleus of the medial longitudinal fasciculus of the tegmentum. These two neurons extend dendrites into the ipsilateral tectum and project axons into the spinal cord. Ablating MeLc and MeLr bilaterally impaired prey capture but spared several other behaviors. Ablating different sets of reticulospinal neurons did not impair prey capture, suggesting a selective function of MeLr and MeLc in this behavior. Ablating MeLc and MeLr neurons unilaterally in conjunction with the contralateral tectum also mostly abolished prey capture, but ablating them together with the ipsilateral tectum had a much smaller effect. These results suggest that MeLc and MeLr function in series with the tectum, as part of a circuit that coordinates prey capture movements.

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PubMed2004

Of lasers, mutants, and see-through brains: functional neuroanatomy in zebrafish.

Behavioral functions are carried out by localized circuits in the brain. Although this modular principle is clearly established, the boundaries of modules, and sometimes even their existence, are still debated. Zebrafish might offer distinct advantages in localizing behaviors to discrete brain regions because of the ability to visualize, record from, and lesion precisely identified populations of neurons in the brain. In addition, genetic screens in zebrafish enable the isolation of mutations that disrupt neural pathways and/or behaviors, as an alternative lesioning technique with complementary strengths to laser ablations. For example, the Mauthner cell, a large identified neuron in the hindbrain, has been postulated to be both necessary and sufficient for the execution of escapes. We discuss in this review how experiments, using laser ablations, calcium imaging, and mutants have eroded this notion. Even in a simple behavior, such as escape, many parallel pathways appear to be involved with no single one being absolutely necessary. Lesion studies and the analysis of behavioral mutants are now also beginning to elucidate the functional architecture of the zebrafish visual system. Although still in an embryonic stage, the neuroanatomy of behaviors in zebrafish has a bright future.

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PubMed2003

Visually guided injection of identified reticulospinal neurons in zebrafish: a survey of spinal arborization patterns.

We report here the pattern of axonal branching for 11 descending cell types in the larval brainstem; eight of these cell types are individually identified neurons. Large numbers of brainstem neurons were retrogradely labeled in living larvae by injecting Texas-red dextran into caudal spinal cord. Subsequently, in each larva a single identified cell was injected in vivo with Alexa 488 dextran, using fluorescence microscopy to guide the injection pipette to the targeted cell. The filling of cells via pressure pulses revealed distinct and often extensive spinal axon collaterals for the different cell types. Previous fills of the Mauthner cell had revealed short, knob-like collaterals. In contrast, the two segmental homologs of the Mauthner cell, cells MiD2cm and MiD3cm, showed axon collaterals with extensive arbors recurring at regular intervals along nearly the full extent of spinal cord. Furthermore, the collaterals of MiD2cm crossed the midline at frequent intervals, yielding bilateral arbors that ran in the rostral-caudal direction. Other medullary reticulospinal cells, as well as cells of the nucleus of the medial longitudinal fasciculus (nMLF), also exhibited extensive spinal collaterals, although the patterns differed for each cell type. For example, nMLF cells had extensive collaterals in caudal medulla and far-rostral spinal cord, but these collaterals became sparse more caudally. Two cell types (CaD and RoL1) showed arbors projecting ventrally from a dorsally situated stem axon. Additional cell-specific features that seemed likely to be of physiological significance were observed. The rostral-caudal distribution of axon collaterals was of particular interest because of its implications for the descending control of the larva's locomotive repertoire. Because the same individual cell types can be identified from fish to fish, these anatomical observations can be directly linked to data obtained in other kinds of experiments. For example, 9 of the 11 cell types examined here have been shown to be active during escape behaviors.

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PubMed2003

Probing neural circuits in the zebrafish: a suite of optical techniques.

The ability to image neural activity in populations of neurons inside an intact animal, while obtaining single-cell or subcellular spatial resolution, has led to several advances in our understanding of vertebrate locomotor control. This result, first reported in a 1995 study of motoneurons in larval zebrafish, was the beginning of a series of technical developments that exploited the transparency and simplicity of the larval CNS. Presented here, in chronological fashion, is a suite of imaging techniques that have extended the ability to probe and optically dissect neural control systems. Included are methodological details pertaining to: (1). the in vivo optical recording of neural activity, (2). the optical dissection of complex neural architectures, and (3). additional fluorescence imaging-based techniques for the anatomical and physiological characterization of these systems. These approaches have provided insights into the descending neural control of escape and other locomotive behaviors, such as swimming and prey capture. The methods employed are discussed in relation to complementary and alternative imaging techniques, including, for example, the Nipkow disk confocal. While these methodologies focus on descending motor control in the larval zebrafish, the extension of such approaches to other neural systems is viewed as a promising and necessary step if neurobiologists are to bridge the gap between synaptic and brain region levels of analysis. The efficiency of optical techniques for surveying the cellular elements of intricate neural systems is of particular relevance because a comprehensive description of such elements is deemed necessary for a precise understanding of vertebrate neural architectures.

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PubMed2002

Evidence for a widespread brain stem escape network in larval zebrafish.

Zebrafish escape behaviors, which typically consist of a C bend, a counter-turn, and a bout of rapid swimming, are initiated by firing of the Mauthner cell and two segmental homologs. However, after laser-ablation of the Mauthner cell and its homologs, escape-like behaviors still occur, albeit at a much longer latency. This might suggest that additional neurons contribute to this behavior. We therefore recorded the activity of other descending neurons in the brain stem using confocal imaging of cells retrogradely labeled with fluorescent calcium indicators. A large majority of identified descending neurons present in the larval zebrafish, including both ipsilaterally and contralaterally projecting reticulospinal neurons, as well as neurons from the nucleus of the medial longitudinal fasciculus, showed short-latency calcium responses after gentle taps to the head of the larva-a stimulus that reliably evokes an escape behavior. Previous studies had associated such in vivo calcium responses with the firing of action potentials, and because all responding cells have axons projecting into to spinal cord, this suggests that these cells are relaying escape-related information to spinal cord. Other identified neurons failed to show consistent calcium responses to escape-eliciting stimuli. In conjunction with previous lesion studies, these results indicate that the neural control systems for turning and swimming behaviors are widely distributed in the larval zebrafish brain stem. The degree of robustness or redundancy of this system has implications for the descending control of vertebrate locomotion.

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