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Left-Right Asymmetry Is Required for the Habenulae to Respond to Both Visual and Olfactory Stimuli

Identifieur interne : 000198 ( Pmc/Checkpoint ); précédent : 000197; suivant : 000199

Left-Right Asymmetry Is Required for the Habenulae to Respond to Both Visual and Olfactory Stimuli

Auteurs : Elena Dreosti [Royaume-Uni, Belgique] ; Nuria Vendrell Llopis [Belgique] ; Matthias Carl [Royaume-Uni, Allemagne] ; Emre Yaksi [Belgique] ; Stephen W. Wilson [Royaume-Uni]

Source :

RBID : PMC:3969106

Abstract

Summary

Left-right asymmetries are most likely a universal feature of bilaterian nervous systems and may serve to increase neural capacity by specializing equivalent structures on left and right sides for distinct roles [1]. However, little is known about how asymmetries are encoded within vertebrate neural circuits and how lateralization influences processing of information in the brain. Consequently, it remains unclear the extent to which lateralization of the nervous system is important for normal cognitive and other brain functions and whether defects in lateralization contribute to neurological deficits [2]. Here we show that sensory responses to light and odor are lateralized in larval zebrafish habenulae and that loss of brain asymmetry leads to concomitant loss of responsiveness to either visual or olfactory stimuli. We find that in wild-type zebrafish, most habenular neurons responding to light are present on the left, whereas neurons responding to odor are more frequent on the right. Manipulations that reverse the direction of brain asymmetry reverse the functional properties of habenular neurons, whereas manipulations that generate either double-left- or double-right-sided brains lead to loss of habenular responsiveness to either odor or light, respectively. Our results indicate that loss of brain lateralization has significant consequences upon sensory processing and circuit function.


Url:
DOI: 10.1016/j.cub.2014.01.016
PubMed: 24508167
PubMed Central: 3969106


Affiliations:


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PMC:3969106

Le document en format XML

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<p>Left-right asymmetries are most likely a universal feature of bilaterian nervous systems and may serve to increase neural capacity by specializing equivalent structures on left and right sides for distinct roles [
<xref rid="bib1" ref-type="bibr">1</xref>
]. However, little is known about how asymmetries are encoded within vertebrate neural circuits and how lateralization influences processing of information in the brain. Consequently, it remains unclear the extent to which lateralization of the nervous system is important for normal cognitive and other brain functions and whether defects in lateralization contribute to neurological deficits [
<xref rid="bib2" ref-type="bibr">2</xref>
]. Here we show that sensory responses to light and odor are lateralized in larval zebrafish habenulae and that loss of brain asymmetry leads to concomitant loss of responsiveness to either visual or olfactory stimuli. We find that in wild-type zebrafish, most habenular neurons responding to light are present on the left, whereas neurons responding to odor are more frequent on the right. Manipulations that reverse the direction of brain asymmetry reverse the functional properties of habenular neurons, whereas manipulations that generate either double-left- or double-right-sided brains lead to loss of habenular responsiveness to either odor or light, respectively. Our results indicate that loss of brain lateralization has significant consequences upon sensory processing and circuit function.</p>
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</back>
</TEI>
<pmc article-type="brief-report">
<pmc-dir>properties open_access</pmc-dir>
<front>
<journal-meta>
<journal-id journal-id-type="nlm-ta">Curr Biol</journal-id>
<journal-id journal-id-type="iso-abbrev">Curr. Biol</journal-id>
<journal-title-group>
<journal-title>Current Biology</journal-title>
</journal-title-group>
<issn pub-type="ppub">0960-9822</issn>
<issn pub-type="epub">1879-0445</issn>
<publisher>
<publisher-name>Cell Press</publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="pmid">24508167</article-id>
<article-id pub-id-type="pmc">3969106</article-id>
<article-id pub-id-type="publisher-id">S0960-9822(14)00017-7</article-id>
<article-id pub-id-type="doi">10.1016/j.cub.2014.01.016</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Report</subject>
</subj-group>
</article-categories>
<title-group>
<article-title>Left-Right Asymmetry Is Required for the Habenulae to Respond to Both Visual and Olfactory Stimuli</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name>
<surname>Dreosti</surname>
<given-names>Elena</given-names>
</name>
<email>e.dreosti@ucl.ac.uk</email>
<xref rid="aff1" ref-type="aff">1</xref>
<xref rid="aff2" ref-type="aff">2</xref>
<xref rid="cor1" ref-type="corresp"></xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Vendrell Llopis</surname>
<given-names>Nuria</given-names>
</name>
<xref rid="aff2" ref-type="aff">2</xref>
<xref rid="aff3" ref-type="aff">3</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Carl</surname>
<given-names>Matthias</given-names>
</name>
<xref rid="aff1" ref-type="aff">1</xref>
<xref rid="aff4" ref-type="aff">4</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Yaksi</surname>
<given-names>Emre</given-names>
</name>
<email>emre.yaksi@nerf.be</email>
<xref rid="aff2" ref-type="aff">2</xref>
<xref rid="aff3" ref-type="aff">3</xref>
<xref rid="aff5" ref-type="aff">5</xref>
<xref rid="cor2" ref-type="corresp">∗∗</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Wilson</surname>
<given-names>Stephen W.</given-names>
</name>
<email>s.wilson@ucl.ac.uk</email>
<xref rid="aff1" ref-type="aff">1</xref>
<xref rid="cor3" ref-type="corresp">∗∗∗</xref>
</contrib>
</contrib-group>
<aff id="aff1">
<label>1</label>
Department of Cell and Developmental Biology, University College London, Gower Street, London WC1E 6BT, UK</aff>
<aff id="aff2">
<label>2</label>
NERF, Kapeldreef 75, 3001 Leuven, Belgium</aff>
<aff id="aff3">
<label>3</label>
KU Leuven, Kapeldreef 75, 3001 Leuven, Belgium</aff>
<aff id="aff4">
<label>4</label>
Department of Cell and Molecular Biology, Medical Faculty Mannheim, University of Heidelberg, Ludolf-Krehl-Strasse 13–17, 68167 Mannheim, Germany</aff>
<aff id="aff5">
<label>5</label>
VIB, Kapeldreef 75, 3001 Leuven, Belgium</aff>
<author-notes>
<corresp id="cor1">
<label></label>
Corresponding author
<email>e.dreosti@ucl.ac.uk</email>
</corresp>
<corresp id="cor2">
<label>∗∗</label>
Corresponding author
<email>emre.yaksi@nerf.be</email>
</corresp>
<corresp id="cor3">
<label>∗∗∗</label>
Corresponding author
<email>s.wilson@ucl.ac.uk</email>
</corresp>
</author-notes>
<pub-date pub-type="pmc-release">
<day>17</day>
<month>2</month>
<year>2014</year>
</pub-date>
<pmc-comment> PMC Release delay is 0 months and 0 days and was based on .</pmc-comment>
<pub-date pub-type="ppub">
<day>17</day>
<month>2</month>
<year>2014</year>
</pub-date>
<volume>24</volume>
<issue>4</issue>
<fpage>440</fpage>
<lpage>445</lpage>
<history>
<date date-type="received">
<day>21</day>
<month>11</month>
<year>2013</year>
</date>
<date date-type="rev-recd">
<day>6</day>
<month>1</month>
<year>2014</year>
</date>
<date date-type="accepted">
<day>9</day>
<month>1</month>
<year>2014</year>
</date>
</history>
<permissions>
<copyright-statement>© 2014 The Authors</copyright-statement>
<copyright-year>2014</copyright-year>
<license license-type="CC BY" xlink:href="http://creativecommons.org/licenses/by/3.0/">
<license-p>This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.</license-p>
</license>
</permissions>
<abstract>
<title>Summary</title>
<p>Left-right asymmetries are most likely a universal feature of bilaterian nervous systems and may serve to increase neural capacity by specializing equivalent structures on left and right sides for distinct roles [
<xref rid="bib1" ref-type="bibr">1</xref>
]. However, little is known about how asymmetries are encoded within vertebrate neural circuits and how lateralization influences processing of information in the brain. Consequently, it remains unclear the extent to which lateralization of the nervous system is important for normal cognitive and other brain functions and whether defects in lateralization contribute to neurological deficits [
<xref rid="bib2" ref-type="bibr">2</xref>
]. Here we show that sensory responses to light and odor are lateralized in larval zebrafish habenulae and that loss of brain asymmetry leads to concomitant loss of responsiveness to either visual or olfactory stimuli. We find that in wild-type zebrafish, most habenular neurons responding to light are present on the left, whereas neurons responding to odor are more frequent on the right. Manipulations that reverse the direction of brain asymmetry reverse the functional properties of habenular neurons, whereas manipulations that generate either double-left- or double-right-sided brains lead to loss of habenular responsiveness to either odor or light, respectively. Our results indicate that loss of brain lateralization has significant consequences upon sensory processing and circuit function.</p>
</abstract>
<abstract abstract-type="graphical">
<title>Graphical Abstract</title>
<fig id="undfig1" position="anchor">
<graphic xlink:href="fx1"></graphic>
</fig>
</abstract>
<abstract abstract-type="author-highlights">
<title>Highlights</title>
<p>
<list list-type="simple">
<list-item id="u0010">
<label></label>
<p>Habenular neuron responses to light and odor stimuli are lateralized</p>
</list-item>
<list-item id="u0015">
<label></label>
<p>Lateralized habenular light responses depend upon the eyes</p>
</list-item>
<list-item id="u0020">
<label></label>
<p>Loss of brain asymmetry leads to a loss of either light or odor responses</p>
</list-item>
</list>
</p>
</abstract>
<abstract abstract-type="teaser">
<p>Dreosti et al. show that sensory responses to light and odor are lateralized in the larval zebrafish habenula and that loss of brain asymmetry leads to a loss of responses to visual or olfactory stimuli, suggesting that brain lateralization may play a significant role in sensory processing and circuit function.</p>
</abstract>
</article-meta>
</front>
<floats-group>
<fig id="fig1">
<label>Figure 1</label>
<caption>
<p>Responses to Visual and Odor Stimuli Are Lateralized in the dHb and Segregated Dorsoventrally in the IPN</p>
<p>(A) Schematic dorsal and sagittal views of 4 days postfertilization (dpf) zebrafish showing left (red) and right (blue) dHb nuclei and their asymmetric afferents from olfactory mitral cells (yellow) arborizing in the right dHb nucleus and parapineal neurons (cyan) arborizing in the left dHb nucleus. Neurons of the left dHb predominantly innervate the dorsal IPN, while neurons of the right dHb innervate the ventral IPN.</p>
<p>(B) Example of a two-photon image of a single z plane of the dHb (14 μm below the skin) of a Tg(
<italic>elavl3</italic>
:GCaMP5G) 4 dpf fish (top) and corresponding color-coded calcium signals that are LR lateralized in dHb neurons in response to a nonlateralized presentation of light (middle) and odor (bottom) stimuli. Each panel is an average of two stimulus trials. The relative change in fluorescence (ΔF/F) is expressed as a percentage.</p>
<p>(C) Example of a two-photon image of a lateral view of the IPN of a Tg(
<italic>elavl3</italic>
:GCaMP5G) 4 dpf fish (top) and corresponding color-coded calcium responses to light (middle) and odor (bottom). Each panel is an average of three trails. Responses to light are predominantly localized in the dorsal IPN, while those to odor are localized in the ventral IPN. Note that the dorsal IPN has a higher basal fluorescence (as does the left dHb nucleus).</p>
<p>Scale bars, 20 μm. D, dorsal; V, ventral; fr, fasciculus retroflexus; IPN, interpeduncular nucleus; dHb, dorsal habenulae; L, left; R, right; mc, mitral cells; Pp, parapineal. See also
<xref rid="app2" ref-type="sec">Figure S1</xref>
.</p>
</caption>
<graphic xlink:href="gr1"></graphic>
</fig>
<fig id="fig2">
<label>Figure 2</label>
<caption>
<p>Functional Responses of Habenular Neurons to Visual and Odor Stimuli</p>
<p>(A) Raw images of four z planes (at 7, 14, 21, and 28 μm depth from surface) of the dHb of a 4 dpf Tg(
<italic>elavl3</italic>
:GCaMP5G) wild-type fry. In the right panels, dHb neuron cell bodies, indicated as regions of interest (ROIs), are color coded in red, blue, violet, or white dependent upon their response to light, odor, both, or neither, respectively. To quantify the number of dHb neurons responding to light and odor, we analyzed the two most-dorsal planes (at 7 and 14 μm) that contained the majority of responding neurons. Only neurons with amplitude responses greater than 2 SDs from the baseline were considered as responding neurons. Neurons that showed inhibition of activity in response to stimulus presentation are not shown. Scale bar, 20 μm.</p>
<p>(B) Graphs showing the time courses (averages of two stimulus presentations) of all individual neurons within one imaging plane, at 14 μm depth, to light (top) and odor (bottom) stimuli. Individual responses are shown in gray, the average of all responses is colored red or blue, and two neurons demonstrating the distinct kinetics of the sensory responses are highlighted in dark gray. The durations of the light and odor stimulation are indicated by the black bars; note the difference in time scale.</p>
<p>See also
<xref rid="app2" ref-type="sec">Figure S2</xref>
.</p>
</caption>
<graphic xlink:href="gr2"></graphic>
</fig>
<fig id="fig3">
<label>Figure 3</label>
<caption>
<p>Developmental Disruption of dHb Asymmetry Leads to Loss of Sensory Responses to Light or Odor</p>
<p>(A–D) Confocal images of the epithalamus of wild-type (A), cold-shocked (B), parapineal-ablated (C), and IWR1-treated (D) Tg(
<italic>foxD3</italic>
:GFP ×
<italic>lhx2a</italic>
:Gap43-YFP) 4 dpf fish showing normally lateralized (LR), reversed (RL), double-right (RR), and double-left (LL) epithalami. Olfactory mitral cell projections (white arrows) terminate in the right dHb nucleus in the wild-type brain (A), terminate in the left dHb in the reversed brain (B), are bilateral in the double-right brain (C), and are reduced/absent in the double-left brain (D). Parapineal neuron projections (pseudocolored cyan) terminate in the left dHb in the wild-type and double-left brain (A and D), terminate in the right dHb in the reversed brain (B), and are reduced/absent in the double-right brain (C).</p>
<p>(E–H) Examples of single z planes of the dHb (as in
<xref rid="fig1" ref-type="fig">Figures 1</xref>
B and
<xref rid="fig2" ref-type="fig">2</xref>
A) of wild-type (E), cold-shocked (F), parapineal-ablated (G), and IWR1-treated (H) Tg(
<italic>foxD3</italic>
:GFP ×
<italic>lhx2a</italic>
:Gap43-YFP) 4 dpf fish as in (A)–(D) showing lateralization of neuronal responses to light and odor. Neuronal cell bodies are shown as ROIs color coded in red, blue, violet, or white depending on whether they responded to light, responded to odor, responded to both light and odor, or were nonresponding. Only neurons with amplitude responses greater than 2 SDs from the prestimulus baseline are considered as responding. Neurons that showed an inhibitory response are not shown.</p>
<p>(I–L) Bar charts showing the percentages of light (red)- versus odor (blue)-responding neurons (normalized to the total number of dHb neurons) in the left and right dHb nuclei for two sampled planes (at depths of 7 and 14 μm) in multiple fish of each of the classes shown in (A)–(D). For the wild-type (I), an average of about 17% of neurons respond to light 20% to odor and 1% to both (n = 8 fish). The LR difference in light responses was significant (p = 4 × 10
<sup>−5</sup>
), as was the LR difference in odor responses (p = 5 × 10
<sup>−4</sup>
;
<sup>∗∗</sup>
p < 0.001, Student’s t test). For reversed fish (J), about 10% of dHb neurons respond on average to light, 14% to odor, and 0.6% to both. LR difference responses was significant to light (p = 0.0056) and odor (p = 0.0072) (n = 7 fish). In double-right-brained fish (K), 21% of neurons were odor responding, with light-responding neurons reduced to 0.5% and those responding to both to 0.2% (n = 8 fish), whereas double-left-brained fish (L) showed an increased percentage of neurons responding to light (35%), a reduced number responding to odor (3%), and 3% responding to both (n = 6 fish). Error bars indicate the SEM.</p>
<p>(M–P) Sagittal views of the IPN in Tg(
<italic>elavl3</italic>
:GCaMP5G) 4 dpf fish showing excitation in response to light (red) and odor (blue), color coded depending on their ΔF/F responses. In the wild-type (M) and reversed (N) fish, light and odor responses are localized in the dorsal and ventral IPN, respectively. In the IPN of the double-left-brained fish (P), virtually all IPN responses were upon light stimulation, whereas in the double-right-brained fish (O), virtually all IPN responses were upon odor stimulation.</p>
<p>Scale bars, 20 μm. D, dorsal; V, ventral; Pp, parapineal; mc, mitral cell axons and terminals; LHb, left habenula nucleus; R Hb, right habenula nucleus. See also
<xref rid="app2" ref-type="sec">Figures S3</xref>
and
<xref rid="app2" ref-type="sec">S4</xref>
.</p>
</caption>
<graphic xlink:href="gr3"></graphic>
</fig>
<fig id="fig4">
<label>Figure 4</label>
<caption>
<p>Asymmetric Responses of left dHb Neurons to Light Are Dependent upon the Eyes</p>
<p>(A and B) Dorsal views of live wild-type (A) and
<italic>chk</italic>
<sup>ne2611</sup>
mutant (B) fish at 4 dpf.</p>
<p>(C) Dorsal view of the dHb nuclei in a
<italic>chk</italic>
<sup>ne2611</sup>
mutant showing that mitral cells inputs remain asymmetrically directed to the right dHb.</p>
<p>(D) Dorsal views of the epithalamus of a Tg(
<italic>elavl3</italic>
:GCaMP5G) 3 dpf fish prior (left) and 4 dpf fish subsequent (right) to ablation of the parapineal (pseudocolored blue).</p>
<p>(E–G) Images of color-coded dHb neuron responses to light (red) and odor (blue) in single z plane of a 4 dpf Tg(
<italic>foxD3</italic>
:GFP × lhx2a:Gap43-YFP)
<italic>chk</italic>
<sup>ne2611</sup>
mutant fish (E), a fish in which eyes were surgically removed at 1 dpf (F), and a Tg(
<italic>foxD3</italic>
:GFP ×
<italic>elavl3</italic>
:GCaMP5G) embryo with late ablation of the parapineal (G).</p>
<p>(H–J) Bar graphs showing average dHb neuron responses to light and odor for
<italic>chk</italic>
mutant (H) eye-ablated (I) and parapineal-ablated (J) fish. Fish without eyes show loss of dHb visual responses, whereas fish without a parapineal still show visual responses. For
<italic>chk</italic>
<sup>ne2611</sup>
mutant and eye-ablated fish, an average of 12% (n = 6 fish) and 16% (n = 6 fish), respectively, of neurons responded to odor. For late parapineal-ablated fish (n = 3 fish), dHb neurons show an asymmetric distribution of responses to light (9% of neurons) and odor (11% of neurons) comparable with that of the wild-type. Error bars indicate the SEM.</p>
<p>Scale bars, 20 μm. Hb, habenulae; Pp, parapineal; LHb, left habenula nucleus; R Hb, right habenula nucleus.</p>
</caption>
<graphic xlink:href="gr4"></graphic>
</fig>
</floats-group>
</pmc>
<affiliations>
<list>
<country>
<li>Allemagne</li>
<li>Belgique</li>
<li>Royaume-Uni</li>
</country>
<region>
<li>Angleterre</li>
<li>Bade-Wurtemberg</li>
<li>District de Karlsruhe</li>
<li>Grand Londres</li>
<li>Province du Brabant flamand</li>
</region>
<settlement>
<li>Heverlee</li>
<li>Londres</li>
<li>Louvain</li>
<li>Mannheim</li>
</settlement>
<orgName>
<li>University College de Londres</li>
</orgName>
</list>
<tree>
<country name="Royaume-Uni">
<region name="Angleterre">
<name sortKey="Dreosti, Elena" sort="Dreosti, Elena" uniqKey="Dreosti E" first="Elena" last="Dreosti">Elena Dreosti</name>
</region>
<name sortKey="Carl, Matthias" sort="Carl, Matthias" uniqKey="Carl M" first="Matthias" last="Carl">Matthias Carl</name>
<name sortKey="Wilson, Stephen W" sort="Wilson, Stephen W" uniqKey="Wilson S" first="Stephen W." last="Wilson">Stephen W. Wilson</name>
</country>
<country name="Belgique">
<region name="Province du Brabant flamand">
<name sortKey="Dreosti, Elena" sort="Dreosti, Elena" uniqKey="Dreosti E" first="Elena" last="Dreosti">Elena Dreosti</name>
</region>
<name sortKey="Vendrell Llopis, Nuria" sort="Vendrell Llopis, Nuria" uniqKey="Vendrell Llopis N" first="Nuria" last="Vendrell Llopis">Nuria Vendrell Llopis</name>
<name sortKey="Vendrell Llopis, Nuria" sort="Vendrell Llopis, Nuria" uniqKey="Vendrell Llopis N" first="Nuria" last="Vendrell Llopis">Nuria Vendrell Llopis</name>
<name sortKey="Yaksi, Emre" sort="Yaksi, Emre" uniqKey="Yaksi E" first="Emre" last="Yaksi">Emre Yaksi</name>
<name sortKey="Yaksi, Emre" sort="Yaksi, Emre" uniqKey="Yaksi E" first="Emre" last="Yaksi">Emre Yaksi</name>
<name sortKey="Yaksi, Emre" sort="Yaksi, Emre" uniqKey="Yaksi E" first="Emre" last="Yaksi">Emre Yaksi</name>
</country>
<country name="Allemagne">
<region name="Bade-Wurtemberg">
<name sortKey="Carl, Matthias" sort="Carl, Matthias" uniqKey="Carl M" first="Matthias" last="Carl">Matthias Carl</name>
</region>
</country>
</tree>
</affiliations>
</record>

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