A SLM2 Feedback Pathway Controls Cortical Network Activity and Mouse Behavior

Ingrid Ehrmann, Matthew R Gazzara, Vittoria Pagliarini, Caroline Dalgliesh, Mahsa Kheirollahi-Chadegani, Yaobo Xu, Eleonora Cesari, Marina Danilenko, Marie Maclennan, Kate Lowdon, Tanja Vogel, Piia Keskivali-Bond, Sara Wells, Heather Cater, Philippe Fort, Mauro Santibanez-Koref, Silvia Middei, Claudio Sette, Gavin J. Clowry, Yoseph BarashMark O Cunningham, David J. Elliott

Research output: Contribution to journalArticle

Abstract

The brain is made up of trillions of synaptic connections that together form neural networks needed for normal brain function and behavior. SLM2 is a member of a conserved family of RNA binding proteins, including Sam68 and SLM1, that control splicing of Neurexin1-3 pre-mRNAs. Whether SLM2 affects neural network activity is unknown. Here, we find that SLM2 levels are maintained by a homeostatic feedback control pathway that predates the divergence of SLM2 and Sam68. SLM2 also controls the splicing of Tomosyn2, LysoPLD/ATX, Dgkb, Kif21a, and Cask, each of which are important for synapse function. Cortical neural network activity dependent on synaptic connections between SLM2-expressing-pyramidal neurons and interneurons is decreased in Slm2-null mice. Additionally, these mice are anxious and have a decreased ability to recognize novel objects. Our data reveal a pathway of SLM2 homeostatic auto-regulation controlling brain network activity and behavior.

Original languageEnglish
Pages (from-to)3269-3280
Number of pages12
JournalCell Reports
Volume17
Issue number12
DOIs
Publication statusPublished - Dec 20 2016

Fingerprint

Brain
Neural networks
Feedback
Aptitude
RNA-Binding Proteins
Pyramidal Cells
RNA Precursors
Interneurons
Prednisolone
Synapses
Neurons
Feedback control

Keywords

  • Journal Article

Cite this

Ehrmann, I., Gazzara, M. R., Pagliarini, V., Dalgliesh, C., Kheirollahi-Chadegani, M., Xu, Y., ... Elliott, D. J. (2016). A SLM2 Feedback Pathway Controls Cortical Network Activity and Mouse Behavior. Cell Reports, 17(12), 3269-3280. https://doi.org/10.1016/j.celrep.2016.12.002

A SLM2 Feedback Pathway Controls Cortical Network Activity and Mouse Behavior. / Ehrmann, Ingrid; Gazzara, Matthew R; Pagliarini, Vittoria; Dalgliesh, Caroline; Kheirollahi-Chadegani, Mahsa; Xu, Yaobo; Cesari, Eleonora; Danilenko, Marina; Maclennan, Marie; Lowdon, Kate; Vogel, Tanja; Keskivali-Bond, Piia; Wells, Sara; Cater, Heather; Fort, Philippe; Santibanez-Koref, Mauro; Middei, Silvia; Sette, Claudio; Clowry, Gavin J.; Barash, Yoseph; Cunningham, Mark O; Elliott, David J.

In: Cell Reports, Vol. 17, No. 12, 20.12.2016, p. 3269-3280.

Research output: Contribution to journalArticle

Ehrmann, I, Gazzara, MR, Pagliarini, V, Dalgliesh, C, Kheirollahi-Chadegani, M, Xu, Y, Cesari, E, Danilenko, M, Maclennan, M, Lowdon, K, Vogel, T, Keskivali-Bond, P, Wells, S, Cater, H, Fort, P, Santibanez-Koref, M, Middei, S, Sette, C, Clowry, GJ, Barash, Y, Cunningham, MO & Elliott, DJ 2016, 'A SLM2 Feedback Pathway Controls Cortical Network Activity and Mouse Behavior', Cell Reports, vol. 17, no. 12, pp. 3269-3280. https://doi.org/10.1016/j.celrep.2016.12.002
Ehrmann I, Gazzara MR, Pagliarini V, Dalgliesh C, Kheirollahi-Chadegani M, Xu Y et al. A SLM2 Feedback Pathway Controls Cortical Network Activity and Mouse Behavior. Cell Reports. 2016 Dec 20;17(12):3269-3280. https://doi.org/10.1016/j.celrep.2016.12.002
Ehrmann, Ingrid ; Gazzara, Matthew R ; Pagliarini, Vittoria ; Dalgliesh, Caroline ; Kheirollahi-Chadegani, Mahsa ; Xu, Yaobo ; Cesari, Eleonora ; Danilenko, Marina ; Maclennan, Marie ; Lowdon, Kate ; Vogel, Tanja ; Keskivali-Bond, Piia ; Wells, Sara ; Cater, Heather ; Fort, Philippe ; Santibanez-Koref, Mauro ; Middei, Silvia ; Sette, Claudio ; Clowry, Gavin J. ; Barash, Yoseph ; Cunningham, Mark O ; Elliott, David J. / A SLM2 Feedback Pathway Controls Cortical Network Activity and Mouse Behavior. In: Cell Reports. 2016 ; Vol. 17, No. 12. pp. 3269-3280.
@article{89b632d1325244fa928f0bb8006124ef,
title = "A SLM2 Feedback Pathway Controls Cortical Network Activity and Mouse Behavior",
abstract = "The brain is made up of trillions of synaptic connections that together form neural networks needed for normal brain function and behavior. SLM2 is a member of a conserved family of RNA binding proteins, including Sam68 and SLM1, that control splicing of Neurexin1-3 pre-mRNAs. Whether SLM2 affects neural network activity is unknown. Here, we find that SLM2 levels are maintained by a homeostatic feedback control pathway that predates the divergence of SLM2 and Sam68. SLM2 also controls the splicing of Tomosyn2, LysoPLD/ATX, Dgkb, Kif21a, and Cask, each of which are important for synapse function. Cortical neural network activity dependent on synaptic connections between SLM2-expressing-pyramidal neurons and interneurons is decreased in Slm2-null mice. Additionally, these mice are anxious and have a decreased ability to recognize novel objects. Our data reveal a pathway of SLM2 homeostatic auto-regulation controlling brain network activity and behavior.",
keywords = "Journal Article",
author = "Ingrid Ehrmann and Gazzara, {Matthew R} and Vittoria Pagliarini and Caroline Dalgliesh and Mahsa Kheirollahi-Chadegani and Yaobo Xu and Eleonora Cesari and Marina Danilenko and Marie Maclennan and Kate Lowdon and Tanja Vogel and Piia Keskivali-Bond and Sara Wells and Heather Cater and Philippe Fort and Mauro Santibanez-Koref and Silvia Middei and Claudio Sette and Clowry, {Gavin J.} and Yoseph Barash and Cunningham, {Mark O} and Elliott, {David J.}",
note = "Copyright {\circledC} 2016 The Author(s). Published by Elsevier Inc. All rights reserved.",
year = "2016",
month = "12",
day = "20",
doi = "10.1016/j.celrep.2016.12.002",
language = "English",
volume = "17",
pages = "3269--3280",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "12",

}

TY - JOUR

T1 - A SLM2 Feedback Pathway Controls Cortical Network Activity and Mouse Behavior

AU - Ehrmann, Ingrid

AU - Gazzara, Matthew R

AU - Pagliarini, Vittoria

AU - Dalgliesh, Caroline

AU - Kheirollahi-Chadegani, Mahsa

AU - Xu, Yaobo

AU - Cesari, Eleonora

AU - Danilenko, Marina

AU - Maclennan, Marie

AU - Lowdon, Kate

AU - Vogel, Tanja

AU - Keskivali-Bond, Piia

AU - Wells, Sara

AU - Cater, Heather

AU - Fort, Philippe

AU - Santibanez-Koref, Mauro

AU - Middei, Silvia

AU - Sette, Claudio

AU - Clowry, Gavin J.

AU - Barash, Yoseph

AU - Cunningham, Mark O

AU - Elliott, David J.

N1 - Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

PY - 2016/12/20

Y1 - 2016/12/20

N2 - The brain is made up of trillions of synaptic connections that together form neural networks needed for normal brain function and behavior. SLM2 is a member of a conserved family of RNA binding proteins, including Sam68 and SLM1, that control splicing of Neurexin1-3 pre-mRNAs. Whether SLM2 affects neural network activity is unknown. Here, we find that SLM2 levels are maintained by a homeostatic feedback control pathway that predates the divergence of SLM2 and Sam68. SLM2 also controls the splicing of Tomosyn2, LysoPLD/ATX, Dgkb, Kif21a, and Cask, each of which are important for synapse function. Cortical neural network activity dependent on synaptic connections between SLM2-expressing-pyramidal neurons and interneurons is decreased in Slm2-null mice. Additionally, these mice are anxious and have a decreased ability to recognize novel objects. Our data reveal a pathway of SLM2 homeostatic auto-regulation controlling brain network activity and behavior.

AB - The brain is made up of trillions of synaptic connections that together form neural networks needed for normal brain function and behavior. SLM2 is a member of a conserved family of RNA binding proteins, including Sam68 and SLM1, that control splicing of Neurexin1-3 pre-mRNAs. Whether SLM2 affects neural network activity is unknown. Here, we find that SLM2 levels are maintained by a homeostatic feedback control pathway that predates the divergence of SLM2 and Sam68. SLM2 also controls the splicing of Tomosyn2, LysoPLD/ATX, Dgkb, Kif21a, and Cask, each of which are important for synapse function. Cortical neural network activity dependent on synaptic connections between SLM2-expressing-pyramidal neurons and interneurons is decreased in Slm2-null mice. Additionally, these mice are anxious and have a decreased ability to recognize novel objects. Our data reveal a pathway of SLM2 homeostatic auto-regulation controlling brain network activity and behavior.

KW - Journal Article

U2 - 10.1016/j.celrep.2016.12.002

DO - 10.1016/j.celrep.2016.12.002

M3 - Article

C2 - 28009295

VL - 17

SP - 3269

EP - 3280

JO - Cell Reports

JF - Cell Reports

SN - 2211-1247

IS - 12

ER -