Perception into Action: The Direction of Escape in Larval Zebrafish

Authors:

Lily McNulty, Mariela Petkova, Alex Chen, Vickie Wang, Florian Engert

Date Created:

2025-01-01

Course Title:

Professor:

Not specified

About Paper:

If an animal sees a fast-approaching object, also known as a the right M cell. By reconstructing their postsynaptic partners, looming stimulus, it must escape quickly in case it’s a predator. we aim to compare connectivity patterns. Interestingly, the optic Studies have shown that when the looming object appears on one tectum cells send input directly to the ipsilateral M cell, which, side of the visual field, zebrafish escape in the opposite direction.if stimulated, would cause the wrong direction of escape. This This escape is called a C-start and is controlled by the Mauthner causes us to hypothesize that the encoding of direction is mediated (M) cell. Visual information travels from the retina to the optic by interneurons. Preliminary reconstructions show the existence tectum, which signals the M cells. However, it is unknown how of many interneurons that send signals to both M cells, as well the looming direction is encoded, as there are only two M cells and as spiral fiber neurons that connect to the correct M cell at the they cannot form a spatial map. This project aims to uncover how axon hillock. A mechanistic interpretation of these connectivity this encoding occurs. To investigate, we are using connectomics, pathways is that the bilaterally-projecting cells lower the threshold where we can reconstruct neurons and their partners from electron for the M cells to fire, and the spiral fiber neurons encode the microscopy images of the larval zebrafish brain. We are focusing direction. Overall, this project aims to discover the ways in which on four cells in the right optic tectum that receive information direction for escapes can be encoded and is also an example of how from different parts of the visual field and connect directly to connectomics can be used to discover specific circuits in the brain. Identifying Neural Connections Between Persistent and Passive States in Larval Zebrafish Kaden Moore-Kosslow, Marc Duque Ramirez, Mariela Petkova Harvard College | Lowell House | Neuroscience | 2028 In nature, animals regularly decide between persistence and DRN neurons projects into the locus coeruleus (LC). The LC disengagement. Previous research studying model zebrafish is the primary production center of noradrenaline, the driving larvae identified the neuronal circuits controlling each behavioralneurotransmitter involved in the NE-MO region. Although it state. These are the serotonergic motor learning system for does not yet indicate direct interaction between the behavioral persistence (5-HT) and the noradrenergic astroglial circuit for circuits, the discovery of 5-HT to LC linkage could suggest passivity (NE-MO). The opposing nature of these two circuits—an an inhibitory role of the serotonergic circuit on noradrenaline organism cannot be both persistent and passive simultaneously— production, which may be the ultimate suppressive factor for suggests that the activity of one should suppress the other. Our NE-MO. To verify this, we are currently analyzing existing researchaimedtoinvestigatethepresenceofaninhibitorypathway calcium activity traces of the serotonergic DRN neurons and their between the 5-HT and NE-MO circuits. Using a connectomic postsynaptic partners in the LC. More specifically, we are studying dataset of a larval zebrafish brain, we reconstructed the neurons data collected from experimental setups inducing persistence or of the dorsal raphe nucleus (DRN), a known evolutionarily passivity in zebrafish. If serotonergic DRN activity negatively conserved behavioral switchboard that drives persistence in the correlates with LC partners, this would imply that the 5-HT 5-HT circuit. Within the DRN, there exists a population of circuit inhibits LC activation, suppressing NE-MO and preventing serotonergic neurons responsible for the persistence circuit, and passivity. More broadly, this work uniquely integrates neural we identified this population based on morphology. We mapped activity and connectivity to uncover mechanisms driving internal synaptic connections, revealing that a subset of serotonergic state transitions—a key challenge in systems neuroscience. Understanding How Brain Circuits Coordinate with Heart Function Shikha Patel, Kristian Herrera, Mariela Petkova, Florian Engert Brandeis University | Neuroscience | 2028 The brain regulates internal organ function by coordinating nucleus. To determine how these regions may interact, we next autonomic activity, including control of heart function. While reconstructed the postsynaptic partners of these neurons. Our it is well established that multiple brain regions project to vagalreconstructionsrevealthatwhileneuronsfromallthreeregionscan motor neurons (VMNs), which activate the parasympathetic “rest- influence heart rate via VMNs, their outputs extend to additional, and-digest” response, how their downstream brain circuits are distinct targets. Specifically, neurons in the hindbrain project organized remains unknown. A key question is whether multiple not only to heart-related areas but also to regions controlling the brain regions coordinate together or operate independently to pharynx,gills,andjaw. Thispatternsuggeststhateachbrainregion control heart function. To address this, we use larval zebrafish assends outputs to functionally distinct postsynaptic populations. a model system due to their accessibility for whole-brain circuit These findings support an independent circuit model, where the mapping using connectomics. Utilizing electron microscopy PoA, AP, and hindbrain regions regulate heart rate separately data from a 6-day-old larval zebrafish, we first identified and while also engaging with other organ and brain systems. This reconstructed neurons that are presynaptic to the vagal motor work provides a framework for understanding how internal states neurons that control the heart. Here, we found three key brain are coordinated at the circuit level and highlights how distinct regions: the preoptic area (POA), the area postrema (AP), and brain regions integrate heart regulation with broader physiological a hindbrain region homologous to the mammalian parabrachial control. 158 Molecular and Cellular Biology Summer Connectomics Internship for Outreach Neuroscience

Abstract:

If an animal sees a fast-approaching object, also known as a the right M cell. By reconstructing their postsynaptic partners, looming stimulus, it must escape quickly in case it’s a predator. we aim to compare connectivity patterns. Interestingly, the optic Studies have shown that when the looming object appears on one tectum cells send input directly to the ipsilateral M cell, which, side of the visual field, zebrafish escape in the opposite direction.if stimulated, would cause the wrong direction of escape. This This escape is called a C-start and is controlled by the Mauthner causes us to hypothesize that the encoding of direction is mediated (M) cell. Visual information travels from the retina to the optic by interneurons. Preliminary reconstructions show the existence tectum, which signals the M cells. However, it is unknown how of many interneurons that send signals to both M cells, as well the looming direction is encoded, as there are only two M cells and as spiral fiber neurons that connect to the correct M cell at the they cannot form a spatial map. This project aims to uncover how axon hillock. A mechanistic interpretation of these connectivity this encoding occurs. To investigate, we are using connectomics, pathways is that the bilaterally-projecting cells lower the threshold where we can reconstruct neurons and their partners from electron for the M cells to fire, and the spiral fiber neurons encode the microscopy images of the larval zebrafish brain. We are focusing direction. Overall, this project aims to discover the ways in which on four cells in the right optic tectum that receive information direction for escapes can be encoded and is also an example of how from different parts of the visual field and connect directly to connectomics can be used to discover specific circuits in the brain. Identifying Neural Connections Between Persistent and Passive States in Larval Zebrafish Kaden Moore-Kosslow, Marc Duque Ramirez, Mariela Petkova Harvard College | Lowell House | Neuroscience | 2028 In nature, animals regularly decide between persistence and DRN neurons projects into the locus coeruleus (LC). The LC disengagement. Previous research studying model zebrafish is the primary production center of noradrenaline, the driving larvae identified the neuronal circuits controlling each behavioralneurotransmitter involved in the NE-MO region. Although it state. These are the serotonergic motor learning system for does not yet indicate direct interaction between the behavioral persistence (5-HT) and the noradrenergic astroglial circuit for circuits, the discovery of 5-HT to LC linkage could suggest passivity (NE-MO). The opposing nature of these two circuits—an an inhibitory role of the serotonergic circuit on noradrenaline organism cannot be both persistent and passive simultaneously— production, which may be the ultimate suppressive factor for suggests that the activity of one should suppress the other. Our NE-MO. To verify this, we are currently analyzing existing researchaimedtoinvestigatethepresenceofaninhibitorypathway calcium activity traces of the serotonergic DRN neurons and their between the 5-HT and NE-MO circuits. Using a connectomic postsynaptic partners in the LC. More specifically, we are studying dataset of a larval zebrafish brain, we reconstructed the neurons data collected from experimental setups inducing persistence or of the dorsal raphe nucleus (DRN), a known evolutionarily passivity in zebrafish. If serotonergic DRN activity negatively conserved behavioral switchboard that drives persistence in the correlates with LC partners, this would imply that the 5-HT 5-HT circuit. Within the DRN, there exists a population of circuit inhibits LC activation, suppressing NE-MO and preventing serotonergic neurons responsible for the persistence circuit, and passivity. More broadly, this work uniquely integrates neural we identified this population based on morphology. We mapped activity and connectivity to uncover mechanisms driving internal synaptic connections, revealing that a subset of serotonergic state transitions—a key challenge in systems neuroscience. Understanding How Brain Circuits Coordinate with Heart Function Shikha Patel, Kristian Herrera, Mariela Petkova, Florian Engert Brandeis University | Neuroscience | 2028 The brain regulates internal organ function by coordinating nucleus. To determine how these regions may interact, we next autonomic activity, including control of heart function. While reconstructed the postsynaptic partners of these neurons. Our it is well established that multiple brain regions project to vagalreconstructionsrevealthatwhileneuronsfromallthreeregionscan motor neurons (VMNs), which activate the parasympathetic “rest- influence heart rate via VMNs, their outputs extend to additional, and-digest” response, how their downstream brain circuits are distinct targets. Specifically, neurons in the hindbrain project organized remains unknown. A key question is whether multiple not only to heart-related areas but also to regions controlling the brain regions coordinate together or operate independently to pharynx,gills,andjaw. Thispatternsuggeststhateachbrainregion control heart function. To address this, we use larval zebrafish assends outputs to functionally distinct postsynaptic populations. a model system due to their accessibility for whole-brain circuit These findings support an independent circuit model, where the mapping using connectomics. Utilizing electron microscopy PoA, AP, and hindbrain regions regulate heart rate separately data from a 6-day-old larval zebrafish, we first identified and while also engaging with other organ and brain systems. This reconstructed neurons that are presynaptic to the vagal motor work provides a framework for understanding how internal states neurons that control the heart. Here, we found three key brain are coordinated at the circuit level and highlights how distinct regions: the preoptic area (POA), the area postrema (AP), and brain regions integrate heart regulation with broader physiological a hindbrain region homologous to the mammalian parabrachial control. 158 Molecular and Cellular Biology Summer Connectomics Internship for Outreach Neuroscience

Source:

Harvard / Isaac Haber, Mariela Petkova, Florian Engert / 2025

Topics:

circuit, neuron, cell, brain, zebrafish, region, heart, direction, escape, larval, serotonergic, partner

Co-authors:

@lilymcnulty438 , @marielapetkova437 , @alexchen439 , @vickiewang440 , @florianengert326