Laser Ablations Reveal Functional Relationships of Segmental Hindbrain Neurons in Zebrafish

Liu, Katharine S.; Fetcho, Joseph R.

doi:10.1016/s0896-6273(00)80783-7

Cited by 380 publications

(442 citation statements)

References 27 publications

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“…The discrete organization that we see, which differs from previously observed distributed activity 4,18,30 , is made apparent by the ability to evoke simple motor patterns with controlled visual stimulation. The fact that more complex behaviors are associated with distributed activation of many neurons is consistent with a model in which subsets of neurons initiate distinct components of the behavior 31,32 .Additional evidence for a distributed motor command has come from a number of studies that found that ablations do not abolish specific behaviors, although they can alter their latency and kinematics 16,17,[33][34][35] . Here, an ablation guided by an observed functional organization was able to completely abolish a specific behavior; optomotor turns in one direction were specifically eliminated by ablation of the small number of cells responsive to turn-evoking stimuli.…”

mentioning

confidence: 53%

“…Additional evidence for a distributed motor command has come from a number of studies that found that ablations do not abolish specific behaviors, although they can alter their latency and kinematics 16,17,[33][34][35] . Here, an ablation guided by an observed functional organization was able to completely abolish a specific behavior; optomotor turns in one direction were specifically eliminated by ablation of the small number of cells responsive to turn-evoking stimuli.…”

Section: Discussionmentioning

confidence: 99%

“…5a-c). To test the efficacy of this technique, we ablated the Mauthner cell and its segmental homologs, reproducing the side-specific increase in escape response latency that was found in previous studies 16 (Supplementary Movie 1 online).…”

Section: Laser Ablation Of Turning Neuronsmentioning

confidence: 99%

“…Activity in the Mauthner cell is sufficient to initiate escape sequences in goldfish 15 . Ablation of these neurons in zebrafish can eliminate short-latency, high-performance turns in response to tactile and acoustic stimuli, but the fish still show slower, long-latency responses 16,17 , and tactile stimuli have been found to activate virtually all reticulospinal neurons 18 . Similar widespread activation of motor-control neurons has been observed in both invertebrate 19,20 and vertebrate model systems 21,22 .…”

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Control of visually guided behavior by distinct populations of spinal projection neurons

et al. 2008

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A basic question in the field of motor control is how different actions are represented by activity in spinal projection neurons. We used a new behavioral assay to identify visual stimuli that specifically drive basic motor patterns in zebrafish. These stimuli evoked consistent patterns of neural activity in the neurons projecting to the spinal cord, which we could map throughout the entire population using in vivo two-photon calcium imaging. We found that stimuli that drive distinct behaviors activated distinct subsets of projection neurons, consisting, in some cases, of just a few cells. This stands in contrast to the distributed activation seen for more complex behaviors. Furthermore, targeted cell by cell ablations of the neurons associated with evoked turns abolished the corresponding behavioral response. This description of the functional organization of the zebrafish motor system provides a framework for identifying the complete circuit underlying a vertebrate behavior.In a behaving animal, the brain communicates its intentions to muscles via the pattern of activity in descending projection neurons 1 . In vertebrates, these cells respond to the detection and processing of sensory stimuli and transmit their motor command to the local networks of the spinal cord, which in turn initiate and coordinate muscle contraction 2 . A fundamental question in neuroscience is how the commands that initiate behaviors are encoded in the activation of these projection neurons 3-5 .The spinal projection system of fish provides an excellent model for studying this code 6 . A diverse range of swimming behaviors can be seen in 6-d-old zebrafish 7-9 that are mediated by a descending projection to the spinal cord consisting of fewer than 300 neurons 10,11 . These neurons are easily labeled with fluorescent indicators 12 , optically accessible with modern imaging techniques and arranged in a stereotyped pattern such that the same cells or groups of cells can easily be identified from one fish to the next 13 . These neurons are morphologically diverse, with distinct dendritic fields and axonal projection patterns 13,14 , suggesting that they serve different behavioral functions. Nevertheless, determining how differing patterns of activity in these spinal projection neurons produce different motor outputs has proved to be difficult. 23,24 , the actual command is encoded in distributed activity throughout the population of control neurons 2 .The swimming behaviors of zebrafish, including the complex sequence of turns and swims that make up the escape response, can be broken down into basic kinematic elements 8 . It is possible that the motor commands for these basic behaviors originate from distinct populations of neurons, which when combined would appear as a `distributed command'. We found that whole-field visual motion, with the direction dynamically locked to the fish's body axis, is able to selectively evoke some of these basic swim patterns. Calcium imaging of stimulus-evoked responses in the complete population of n...

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confidence: 53%

Section: Discussionmentioning

confidence: 99%

Section: Laser Ablation Of Turning Neuronsmentioning

confidence: 99%

mentioning

confidence: 99%

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Control of visually guided behavior by distinct populations of spinal projection neurons

et al. 2008

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“…Laser ablation has been applied to study locomotor networks. In zebrafish cyan (488-nm) laser exposure for 10-12 min photoablated reticulospinal neurons by augmenting the toxicity of indicator dyes, revealing specific roles for Mauthner cells and their homologs in short-latency escape behaviors (19). UV lasers (≈400 nm) were used in Caenorbabditis elegans to investigate locomotion, chemotaxis, and mechanosensation (20).…”

Section: Discussionmentioning

confidence: 99%

Cumulative lesioning of respiratory interneurons disrupts and precludes motor rhythms in vitro

Hayes

Wang²,

Negro³

2012

Proc. Natl. Acad. Sci. U.S.A.

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How brain functions degenerate in the face of progressive cell loss is an important issue that pertains to neurodegenerative diseases and basic properties of neural networks. We developed an automated system that uses two-photon microscopy to detect rhythmic neurons from calcium activity, and then individually laser ablates the targets while monitoring network function in real time. We applied this system to the mammalian respiratory oscillator located in the pre-Bötzinger Complex (preBötC) of the ventral medulla, which spontaneously generates breathing-related motor activity in vitro. Here, we show that cumulatively deleting preBötC neurons progressively decreases respiratory frequency and the amplitude of motor output. On average, the deletion of 120 ± 45 neurons stopped spontaneous respiratory rhythm, and our data suggest ≈82% of the rhythm-generating neurons remain unlesioned. Cumulative ablations in other medullary respiratory regions did not affect frequency but diminished the amplitude of motor output to a lesser degree. These results suggest that the preBötC can sustain insults that destroy no more than ≈18% of its constituent interneurons, which may have implications for the onset of respiratory pathologies in disease states.central pattern generator | calcium imaging | brainstem C entral pattern generator (CPG) networks produce coordinated motor patterns that underlie behaviors such as breathing, locomotion, and chewing (1, 2). A key issue is not just which cell types generate these patterns of activity, but how many? This question pertains to whether and how cumulative cell loss will impair and, possibly preclude, network function.Breathing consists of inspiratory and expiratory phases. The preBötzinger Complex (preBötC) of the medulla putatively contains the inspiratory CPG (3, 4). Over several days in vivo, saporinmediated destruction of preBötC neurons that express neurokinin-1 receptors (NK1Rs) causes sleep-disordered breathing and fatal respiratory pathology (5, 6). Similarly, acute cell-silencing of a subset of the same NK1R-expressing population of preBötC neurons stops spontaneous breathing in awake adult rats (7). These studies helped to determine the cellular composition of the preBötC and confirmed that it was essential for breathing in an otherwise intact animal, but could not measure the resiliency of the preBötC when faced with silencing or deleting its core piecewise.We examined this issue by using slice preparations that capture the preBötC and spontaneously generate fictive breathing-related activity in vitro. We developed a computer-automated system that detects rhythmically active interneurons via two-photon calcium imaging, stores their physical locations in memory, and then laser ablates the targets sequentially, while electrophysiologically monitoring the motor output of the circuit. We applied this system to the preBötC to test the hypothesis that piecewise destruction of the CPG core would cause graded loss of motor activity up to rhythm cessation. We surmised that this effect ...

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Functional Regeneration in the Larval Zebrafish Spinal Cord

Bhatt

Patzelova

McLean

et al. 2006

Model Organisms in Spinal Cord Regeneration

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Laser Ablations Reveal Functional Relationships of Segmental Hindbrain Neurons in Zebrafish

Cited by 380 publications

References 27 publications

Control of visually guided behavior by distinct populations of spinal projection neurons

Control of visually guided behavior by distinct populations of spinal projection neurons

Cumulative lesioning of respiratory interneurons disrupts and precludes motor rhythms in vitro

Functional Regeneration in the Larval Zebrafish Spinal Cord

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