Synaptic scaffold evolution generated components of vertebrate cognitive complexity

Jess Nithianantharajah; Noboru H. Komiyama; Andrew McKechanie; Mandy Johnstone; Douglas H. Blackwood; David St Clair; Richard D. Emes; Louie N. Van De Lagemaat; Lisa M. Saksida; Timothy J. Bussey; Seth G.N. Grant

doi:10.1038/nn.3276

Synaptic scaffold evolution generated components of vertebrate cognitive complexity

Jess Nithianantharajah, Noboru H. Komiyama, Andrew McKechanie, Mandy Johnstone, Douglas H. Blackwood, David St Clair, Richard D. Emes, Louie N. Van De Lagemaat, Lisa M. Saksida, Timothy J. Bussey, Seth G.N. Grant^*

^*Corresponding author for this work

Applied Medicine

Research output: Contribution to journal › Article › peer-review

199 Citations (Scopus)

Abstract

The origins and evolution of higher cognitive functions, including complex forms of learning, attention and executive functions, are unknown. A potential mechanism driving the evolution of vertebrate cognition early in the vertebrate lineage (550 million years ago) was genome duplication and subsequent diversification of postsynaptic genes. Here we report, to our knowledge, the first genetic analysis of a vertebrate gene family in cognitive functions measured using computerized touchscreens. Comparison of mice carrying mutations in each of the four Dlg paralogs showed that simple associative learning required Dlg4, whereas Dlg2 and Dlg3 diversified to have opposing functions in complex cognitive processes. Exploiting the translational utility of touchscreens in humans and mice, testing Dlg2 mutations in both species showed that Dlg2's role in complex learning, cognitive flexibility and attention has been highly conserved over 100 million years. Dlg-family mutations underlie psychiatric disorders, suggesting that genome evolution expanded the complexity of vertebrate cognition at the cost of susceptibility to mental illness.

Original language	English
Pages (from-to)	16-24
Number of pages	9
Journal	Nature Neuroscience
Volume	16
Issue number	1
Early online date	2 Dec 2012
DOIs	https://doi.org/10.1038/nn.3276
Publication status	Published - 2013

Bibliographical note

Acknowledgements
We thank K. Elsegood and D. Fricker for mouse husbandry and genotyping, T.W. Robbins for advice on CANTAB, J. Barnett for assistance with CANTAB control data and T.W. Robbins and T.J. O'Dell for comments on the manuscript. Figure illustration contribution by D.J. Maizels. J.N., N.H.K., L.N.L. and S.G.N.G. was supported by The Wellcome Trust, Genes to Cognition Program, The Medical Research Council (MRC) and European Union programs (Project GENCODYS no. 241995, Project EUROSPIN no. 242498 and Project SYNSYS no. 242167). M.J. was supported by grants from RS Macdonald Charitable Trust and Academy of Medical Sciences/The Wellcome Trust.

Keywords

Cognitive neuroscience
Genome evolution
Learning and memory
Psychiatric disorders

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1038/nn.3276

Cite this

@article{9848b1f223264ab4b9d0c1264bff0b8b,

title = "Synaptic scaffold evolution generated components of vertebrate cognitive complexity",

abstract = "The origins and evolution of higher cognitive functions, including complex forms of learning, attention and executive functions, are unknown. A potential mechanism driving the evolution of vertebrate cognition early in the vertebrate lineage (550 million years ago) was genome duplication and subsequent diversification of postsynaptic genes. Here we report, to our knowledge, the first genetic analysis of a vertebrate gene family in cognitive functions measured using computerized touchscreens. Comparison of mice carrying mutations in each of the four Dlg paralogs showed that simple associative learning required Dlg4, whereas Dlg2 and Dlg3 diversified to have opposing functions in complex cognitive processes. Exploiting the translational utility of touchscreens in humans and mice, testing Dlg2 mutations in both species showed that Dlg2's role in complex learning, cognitive flexibility and attention has been highly conserved over 100 million years. Dlg-family mutations underlie psychiatric disorders, suggesting that genome evolution expanded the complexity of vertebrate cognition at the cost of susceptibility to mental illness.",

keywords = "Cognitive neuroscience, Genome evolution, Learning and memory, Psychiatric disorders",

author = "Jess Nithianantharajah and Komiyama, {Noboru H.} and Andrew McKechanie and Mandy Johnstone and Blackwood, {Douglas H.} and Clair, {David St} and Emes, {Richard D.} and {Van De Lagemaat}, {Louie N.} and Saksida, {Lisa M.} and Bussey, {Timothy J.} and Grant, {Seth G.N.}",

note = "Acknowledgements We thank K. Elsegood and D. Fricker for mouse husbandry and genotyping, T.W. Robbins for advice on CANTAB, J. Barnett for assistance with CANTAB control data and T.W. Robbins and T.J. O'Dell for comments on the manuscript. Figure illustration contribution by D.J. Maizels. J.N., N.H.K., L.N.L. and S.G.N.G. was supported by The Wellcome Trust, Genes to Cognition Program, The Medical Research Council (MRC) and European Union programs (Project GENCODYS no. 241995, Project EUROSPIN no. 242498 and Project SYNSYS no. 242167). M.J. was supported by grants from RS Macdonald Charitable Trust and Academy of Medical Sciences/The Wellcome Trust.",

year = "2013",

doi = "10.1038/nn.3276",

language = "English",

volume = "16",

pages = "16--24",

journal = "Nature Neuroscience",

issn = "1097-6256",

publisher = "Nature Publishing Group",

number = "1",

}

TY - JOUR

T1 - Synaptic scaffold evolution generated components of vertebrate cognitive complexity

AU - Nithianantharajah, Jess

AU - Komiyama, Noboru H.

AU - McKechanie, Andrew

AU - Johnstone, Mandy

AU - Blackwood, Douglas H.

AU - Clair, David St

AU - Emes, Richard D.

AU - Van De Lagemaat, Louie N.

AU - Saksida, Lisa M.

AU - Bussey, Timothy J.

AU - Grant, Seth G.N.

N1 - Acknowledgements We thank K. Elsegood and D. Fricker for mouse husbandry and genotyping, T.W. Robbins for advice on CANTAB, J. Barnett for assistance with CANTAB control data and T.W. Robbins and T.J. O'Dell for comments on the manuscript. Figure illustration contribution by D.J. Maizels. J.N., N.H.K., L.N.L. and S.G.N.G. was supported by The Wellcome Trust, Genes to Cognition Program, The Medical Research Council (MRC) and European Union programs (Project GENCODYS no. 241995, Project EUROSPIN no. 242498 and Project SYNSYS no. 242167). M.J. was supported by grants from RS Macdonald Charitable Trust and Academy of Medical Sciences/The Wellcome Trust.

PY - 2013

Y1 - 2013

N2 - The origins and evolution of higher cognitive functions, including complex forms of learning, attention and executive functions, are unknown. A potential mechanism driving the evolution of vertebrate cognition early in the vertebrate lineage (550 million years ago) was genome duplication and subsequent diversification of postsynaptic genes. Here we report, to our knowledge, the first genetic analysis of a vertebrate gene family in cognitive functions measured using computerized touchscreens. Comparison of mice carrying mutations in each of the four Dlg paralogs showed that simple associative learning required Dlg4, whereas Dlg2 and Dlg3 diversified to have opposing functions in complex cognitive processes. Exploiting the translational utility of touchscreens in humans and mice, testing Dlg2 mutations in both species showed that Dlg2's role in complex learning, cognitive flexibility and attention has been highly conserved over 100 million years. Dlg-family mutations underlie psychiatric disorders, suggesting that genome evolution expanded the complexity of vertebrate cognition at the cost of susceptibility to mental illness.

AB - The origins and evolution of higher cognitive functions, including complex forms of learning, attention and executive functions, are unknown. A potential mechanism driving the evolution of vertebrate cognition early in the vertebrate lineage (550 million years ago) was genome duplication and subsequent diversification of postsynaptic genes. Here we report, to our knowledge, the first genetic analysis of a vertebrate gene family in cognitive functions measured using computerized touchscreens. Comparison of mice carrying mutations in each of the four Dlg paralogs showed that simple associative learning required Dlg4, whereas Dlg2 and Dlg3 diversified to have opposing functions in complex cognitive processes. Exploiting the translational utility of touchscreens in humans and mice, testing Dlg2 mutations in both species showed that Dlg2's role in complex learning, cognitive flexibility and attention has been highly conserved over 100 million years. Dlg-family mutations underlie psychiatric disorders, suggesting that genome evolution expanded the complexity of vertebrate cognition at the cost of susceptibility to mental illness.

KW - Cognitive neuroscience

KW - Genome evolution

KW - Learning and memory

KW - Psychiatric disorders

UR - http://www.scopus.com/inward/record.url?scp=84871712720&partnerID=8YFLogxK

U2 - 10.1038/nn.3276

DO - 10.1038/nn.3276

M3 - Article

C2 - 23201973

AN - SCOPUS:84871712720

SN - 1097-6256

VL - 16

SP - 16

EP - 24

JO - Nature Neuroscience

JF - Nature Neuroscience

IS - 1

ER -

Synaptic scaffold evolution generated components of vertebrate cognitive complexity

Abstract

Bibliographical note

Keywords

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this