Disruption of left-right axis specification in Ciona induces molecular, cellular, and functional defects in asymmetric brain structures

Abstract Background Left-right asymmetries are a common feature of metazoans and can be found in a number of organs including the nervous system. These asymmetries are particularly pronounced in the simple central nervous system (CNS) of the swimming tadpole larva of the tunicate Ciona, which displays a chordate ground plan. While common pathway elements for specifying the left/right axis are found among chordates, particularly a requirement for Nodal signaling, Ciona differs temporally from its vertebrate cousins by specifying its axis at the neurula stage, rather than at gastrula. Additionally, Ciona and other ascidians require an intact chorionic membrane for proper left-right specification. Whether such differences underlie distinct specification mechanisms between tunicates and vertebrates will require broad understanding of their influence on CNS formation. Here, we explore the consequences of disrupting left-right axis specification on Ciona larval CNS cellular anatomy, gene expression, synaptic connectivity, and behavior. Results We show that left-right asymmetry disruptions caused by removal of the chorion (dechorionation) are highly variable and present throughout the Ciona larval nervous system. While previous studies have documented disruptions to the conspicuously asymmetric sensory systems in the anterior brain vesicle, we document asymmetries in seemingly symmetric structures such as the posterior brain vesicle and motor ganglion. Moreover, defects caused by dechorionation include misplaced or absent neuron classes, loss of asymmetric gene expression, aberrant synaptic projections, and abnormal behaviors. In the motor ganglion, a brain structure that has been equated with the vertebrate hindbrain, we find that despite the apparent left-right symmetric distribution of interneurons and motor neurons, AMPA receptors are expressed exclusively on the left side, which equates with asymmetric swimming behaviors. We also find that within a population of dechorionated larvae, there is a small percentage with apparently normal left-right specification and approximately equal population with inverted (mirror-image) asymmetry. We present a method based on a behavioral assay for isolating these larvae. When these two classes of larvae (normal and inverted) are assessed in a light dimming assay, they display mirror-image behaviors, with normal larvae responding with counterclockwise swims, while inverted larvae respond with clockwise swims. Conclusions Our findings highlight the importance of left-right specification pathways not only for proper CNS anatomy, but also for correct synaptic connectivity and behavior.

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Left/right asymmetry disruptions and mirror-image reversals to behavior and brain anatomy in Ciona

10.1101/2021.03.03.433807 ◽

2021 ◽

Author(s):

Matthew J. Kourakis ◽

Michaela Bostwick ◽

Amanda Zabriskie ◽

William C. Smith

Keyword(s):

Nervous System ◽

Motor Neurons ◽

Ampa Receptors ◽

Mirror Image ◽

Synaptic Connectivity ◽

Brain Anatomy ◽

Chorionic Membrane ◽

Left Right Asymmetry ◽

And Behavior ◽

Symmetric Structures

ABSTRACTBackgroundLeft-right asymmetries are a common feature of metazoan nervous systems. This is particularly pronounced in the comparatively simple larval central nervous system (CNS) of the tunicate Ciona, whose swimming tadpole larva shows a clear chordate ground plan. While common pathway elements for specifying the left-right axis are found in the chordates, particularly a requirement for Nodal signaling, Ciona differs from its vertebrate cousins by specifying its axis at the neurula stage, rather than at gastrula. Additionally, Ciona, and other ascidians, have a requirement for an intact chorionic membrane for proper left/right specification.ResultsWe present here results showing that left-right asymmetry disruptions caused by removal of the chorion (dechorionation) are highly variable and present throughout the Ciona larval nervous system. While previous studies have documented disruptions to the conspicuously asymmetric sensory systems in the anterior brain vesicle, we document asymmetries in seemingly symmetric structures such as the posterior brain vesicle and motor ganglion. Moreover, defects caused by dechorionation include misplaced or absent neuron classes, loss of asymmetric gene expression, aberrant synaptic connectivity, and abnormal behaviors. In the motor ganglion, a brain structure that has been equated with the vertebrate hindbrain, we find that despite the apparent left/right symmetric distribution of interneurons and motor neurons, AMPA receptors are expressed exclusively on the left side, which equates with asymmetric swimming behaviors. We also find that within a population of dechorionated larvae, there is a small percentage with apparently normal left-right specification, and approximately equal population with inverted (mirror-image) asymmetry. We present a method based on a behavioral assay for isolating these larvae. When these two classes of larvae (normal and inverted) are assessed in a light dimming assay they display mirror-image behaviors, with normal larvae responding with counterclockwise swims, while inverted larvae respond with clockwise swims.ConclusionsOur findings highlight the importance of left-right specification pathways not only for proper CNS anatomy, but also for correct synaptic connectivity and behavior.

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Microbiota regulates visceral pain in the mouse

eLife ◽

10.7554/elife.25887 ◽

2017 ◽

Vol 6 ◽

Cited By ~ 46

Author(s):

Pauline Luczynski ◽

Monica Tramullas ◽

Maria Viola ◽

Fergus Shanahan ◽

Gerard Clarke ◽

...

Keyword(s):

Gene Expression ◽

Spinal Cord ◽

Gut Microbiota ◽

Visceral Pain ◽

Brain Structures ◽

Anterior Cingulate ◽

Cytokine Gene Expression ◽

Visceral Sensitivity ◽

Brain And Behavior ◽

And Behavior

The perception of visceral pain is a complex process involving the spinal cord and higher order brain structures. Increasing evidence implicates the gut microbiota as a key regulator of brain and behavior, yet it remains to be determined if gut bacteria play a role in visceral sensitivity. We used germ-free mice (GF) to assess visceral sensitivity, spinal cord gene expression and pain-related brain structures. GF mice displayed visceral hypersensitivity accompanied by increases in Toll-like receptor and cytokine gene expression in the spinal cord, which were normalized by postnatal colonization with microbiota from conventionally colonized (CC). In GF mice, the volumes of the anterior cingulate cortex (ACC) and periaqueductal grey, areas involved in pain processing, were decreased and enlarged, respectively, and dendritic changes in the ACC were evident. These findings indicate that the gut microbiota is required for the normal visceral pain sensation.

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Gene expression of NMDA and AMPA receptors in different facial motor neurons

The Laryngoscope ◽

10.1002/lary.25575 ◽

2015 ◽

Vol 126 (1) ◽

pp. E6-E11 ◽

Cited By ~ 3

Author(s):

Pei Chen ◽

Jun Song ◽

Linghui Luo ◽

Qing Cheng ◽

Hongjun Xiao ◽

...

Keyword(s):

Gene Expression ◽

Motor Neurons ◽

Ampa Receptors

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Inferring Monosynaptic Connectivity Across Brain Structures In-Vivo

10.1101/2020.10.09.333930 ◽

2020 ◽

Author(s):

Yi Juin Liew ◽

Aurélie Pala ◽

Clarissa J Whitmire ◽

William A Stoy ◽

Craig R Forest ◽

...

Keyword(s):

Large Scale ◽

Ex Vivo ◽

Brain Structures ◽

Network Activity ◽

Data Driven ◽

Synaptic Connectivity ◽

Homologous Region ◽

Neural Activation ◽

And Behavior

Abstract/SummaryAs the tools to simultaneously record electrophysiological signals from large numbers of neurons within and across brain regions become increasingly available, this opens up for the first time the possibility of establishing the details of causal relationships between monosynaptically connected neurons and the patterns of neural activation that underlie perception and behavior. Although recorded activity across synaptically connected neurons has served as the cornerstone for much of what we know about synaptic transmission and plasticity, this has largely been relegated to ex-vivo preparations that enable precise targeting under relatively well-controlled conditions. Analogous studies in-vivo, where image-guided targeting is often not yet possible, rely on indirect, data-driven measures, and as a result such studies have been sparse and the dependence upon important experimental parameters has not been well studied. Here, using in-vivo extracellular single unit recordings in the topographically aligned rodent thalamocortical pathway, we sought to establish a general experimental and computational framework for inferring synaptic connectivity. Specifically, attacking this problem within a statistical signal-detection framework utilizing experimentally recorded data in the ventral-posterior medial (VPm) region of the thalamus and the homologous region in layer 4 of primary somatosensory cortex (S1) revealed a trade-off between network activity levels needed for the data-driven inference and synchronization of nearby neurons within the population that result in masking of synaptic relationships. Taken together, we provide a framework for establishing connectivity in multi-site, multi-electrode recordings based on statistical inference, setting the stage for large-scale assessment of synaptic connectivity within and across brain structures.New & NoteworthyDespite the fact that all brain function relies on the long-range transfer of information across different regions, the tools enabling us to measure connectivity across brain structures are lacking. Here, we provide a statistical framework for identifying and assessing potential monosynaptic connectivity across neuronal circuits from population spiking activity that generalizes to large-scale recording technologies that will help us to better understand the signaling within networks that underlies perception and behavior.

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Gene Expression in The Central Nervous System

10.1016/s0079-6123(08)x6097-2 ◽

1995 ◽

Keyword(s):

Gene Expression ◽

Central Nervous System ◽

Nervous System ◽

The Central Nervous System

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Co-Culture of ES Cell-Derived Motor Neurons and Myotubes Show the Formation of Neuromuscular Junctions and Changes in Gene Expression

Journal of Reconstructive Microsurgery ◽

10.1055/s-2006-949682 ◽

2006 ◽

Vol 22 (06) ◽

Author(s):

Aleid Ruijs ◽

Tateki Kubo ◽

Jae Song ◽

Milan Ranka ◽

Mark Randolph ◽

...

Keyword(s):

Gene Expression ◽

Motor Neurons ◽

Neuromuscular Junctions ◽

Es Cell

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Negative and positive effects of an IAP-LTR on nearby Pcdaα gene expression in the central nervous system and neuroblastoma cell lines

Gene ◽

10.1016/j.gene.2004.04.011 ◽

2004 ◽

Vol 337 ◽

pp. 91-103 ◽

Cited By ~ 10

Author(s):

Hidehiko Sugino ◽

Tomoko Toyama ◽

Yusuke Taguchi ◽

Shigeyuki Esumi ◽

Mitsuhiro Miyazaki ◽

...

Keyword(s):

Gene Expression ◽

Central Nervous System ◽

Nervous System ◽

Cell Lines ◽

Neuroblastoma Cell ◽

Positive Effects ◽

The Central Nervous System ◽

Neuroblastoma Cell Lines

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Your Brain Is Not an Onion With a Tiny Reptile Inside

Current Directions in Psychological Science ◽

10.1177/0963721420917687 ◽

2020 ◽

Vol 29 (3) ◽

pp. 255-260

Author(s):

Joseph Cesario ◽

David J. Johnson ◽

Heather L. Eisthen

Keyword(s):

Nervous System ◽

Behavioral Flexibility ◽

Brain Structures ◽

Introductory Psychology ◽

Complex Structures ◽

Accurate Model ◽

Nervous System Evolution ◽

Neural Evolution ◽

Human Brains ◽

Unanimous Agreement

A widespread misconception in much of psychology is that (a) as vertebrate animals evolved, “newer” brain structures were added over existing “older” brain structures, and (b) these newer, more complex structures endowed animals with newer and more complex psychological functions, behavioral flexibility, and language. This belief, although widely shared in introductory psychology textbooks, has long been discredited among neurobiologists and stands in contrast to the clear and unanimous agreement on these issues among those studying nervous-system evolution. We bring psychologists up to date on this issue by describing the more accurate model of neural evolution, and we provide examples of how this inaccurate view may have impeded progress in psychology. We urge psychologists to abandon this mistaken view of human brains.

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