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 Barash; Mark O. Cunningham; David J. Elliott

doi:10.1016/j.celrep.2016.12.002

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 Barash^*Mark O. Cunningham^*, David J. Elliott^*

^*Autore corrispondente per questo lavoro

Risultato della ricerca: Contributo in rivista › Articolo in rivista › peer review

8 Citazioni (Scopus)

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.

Lingua originale	English
pagine (da-a)	3269-3280
Numero di pagine	12
Rivista	Cell Reports
Volume	17
DOI	https://doi.org/10.1016/j.celrep.2016.12.002
Stato di pubblicazione	Pubblicato - 2016

Keywords

Adaptor Proteins, Signal Transducing
Alternative Splicing
Animals
Behavior, Animal
Biochemistry, Genetics and Molecular Biology (all)
Homeostasis
Mice
Mice, Knockout
Nerve Net
Neural Cell Adhesion Molecules
Neurexin splicing
Pyramidal Cells
RNA Precursors
RNA binding proteins
RNA-Binding Proteins
RNA-seq
Synapses
alternative splicing
brain
gene expression
hippocampus
neuron
transcriptome

Accesso al documento

10.1016/j.celrep.2016.12.002

Altri file e collegamenti

Cita questo

Ehrmann, I., Gazzara, M. R., 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, G. J., ... Elliott, D. J. (2016). A SLM2 Feedback Pathway Controls Cortical Network Activity and Mouse Behavior. Cell Reports, 17, 3269-3280. https://doi.org/10.1016/j.celrep.2016.12.002

@article{f224e1d63c4f4c6da545ba5607a234c0,

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 = "Adaptor Proteins, Signal Transducing, Alternative Splicing, Animals, Behavior, Animal, Biochemistry, Genetics and Molecular Biology (all), Homeostasis, Mice, Mice, Knockout, Nerve Net, Neural Cell Adhesion Molecules, Neurexin splicing, Pyramidal Cells, RNA Precursors, RNA binding proteins, RNA-Binding Proteins, RNA-seq, Synapses, alternative splicing, brain, gene expression, hippocampus, neuron, transcriptome, Adaptor Proteins, Signal Transducing, Alternative Splicing, Animals, Behavior, Animal, Biochemistry, Genetics and Molecular Biology (all), Homeostasis, Mice, Mice, Knockout, Nerve Net, Neural Cell Adhesion Molecules, Neurexin splicing, Pyramidal Cells, RNA Precursors, RNA binding proteins, RNA-Binding Proteins, RNA-seq, Synapses, alternative splicing, brain, gene expression, hippocampus, neuron, transcriptome",

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.}",

year = "2016",

doi = "10.1016/j.celrep.2016.12.002",

language = "English",

volume = "17",

pages = "3269--3280",

journal = "Cell Reports",

issn = "2211-1247",

publisher = "Elsevier B.V.",

}

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, pagg. 3269-3280. https://doi.org/10.1016/j.celrep.2016.12.002

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.

PY - 2016

Y1 - 2016

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 - Adaptor Proteins, Signal Transducing

KW - Alternative Splicing

KW - Animals

KW - Behavior, Animal

KW - Biochemistry, Genetics and Molecular Biology (all)

KW - Homeostasis

KW - Mice

KW - Mice, Knockout

KW - Nerve Net

KW - Neural Cell Adhesion Molecules

KW - Neurexin splicing

KW - Pyramidal Cells

KW - RNA Precursors

KW - RNA binding proteins

KW - RNA-Binding Proteins

KW - RNA-seq

KW - Synapses

KW - alternative splicing

KW - brain

KW - gene expression

KW - hippocampus

KW - neuron

KW - transcriptome

KW - Adaptor Proteins, Signal Transducing

KW - Alternative Splicing

KW - Animals

KW - Behavior, Animal

KW - Biochemistry, Genetics and Molecular Biology (all)

KW - Homeostasis

KW - Mice

KW - Mice, Knockout

KW - Nerve Net

KW - Neural Cell Adhesion Molecules

KW - Neurexin splicing

KW - Pyramidal Cells

KW - RNA Precursors

KW - RNA binding proteins

KW - RNA-Binding Proteins

KW - RNA-seq

KW - Synapses

KW - alternative splicing

KW - brain

KW - gene expression

KW - hippocampus

KW - neuron

KW - transcriptome

UR - http://hdl.handle.net/10807/124733

UR - http://www.sciencedirect.com/science/journal/22111247

U2 - 10.1016/j.celrep.2016.12.002

DO - 10.1016/j.celrep.2016.12.002

M3 - Article

SN - 2211-1247

VL - 17

SP - 3269

EP - 3280

JO - Cell Reports

JF - Cell Reports

ER -

A SLM2 Feedback Pathway Controls Cortical Network Activity and Mouse Behavior

Abstract

Keywords

Accesso al documento

Altri file e collegamenti

Fingerprint

Cita questo