Circadian and homeostatic regulation of structural synaptic plasticity in hypocretin neurons

Lior Appelbaum; Gordon Wang; Tohei Yokogawa; Gemini M. Skariah; Stephen J. Smith; Philippe Mourrain; Emmanuel Mignot

doi:10.1016/j.neuron.2010.09.006

Circadian and homeostatic regulation of structural synaptic plasticity in hypocretin neurons

Lior Appelbaum, Gordon Wang, Tohei Yokogawa, Gemini M. Skariah, Stephen J. Smith, Philippe Mourrain, Emmanuel Mignot

The Mina and Everard Goodman Faculty of Life Sciences

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

149 Scopus citations

Abstract

Neurons exhibit rhythmic activity that ultimately affects behavior such as sleep. In living zebrafish larvae, we used time-lapse two-photon imaging of the presynaptic marker synaptophysin in hypocretin/orexin (HCRT) neurons to determine the dynamics of synaptic modifications during the day and night. We observed circadian rhythmicity in synapse number in HCRT axons. This rhythm is regulated primarily by the circadian clock but is also affected by sleep deprivation. Furthermore, NPTX2, a protein implicated in AMPA receptor clustering, modulates circadian synaptic changes. In zebrafish, nptx2b is a rhythmic gene that is mostly expressed in hypothalamic and pineal gland cells. Arrhythmic transgenic nptx2b overexpression (hcrt:NPTX2b) increases synapse number and abolishes rhythmicity in HCRT axons. Finally, hcrt:NPTX2b fish are resistant to the sleep-promoting effects of melatonin. This behavioral effect is consistent with NPTX2b-mediated increased activity of HCRT circuitry. These data provide real-time in vivo evidence of circadian and homeostatic regulation of structural synaptic plasticity.

Original language	English
Pages (from-to)	87-98
Number of pages	12
Journal	Neuron
Volume	68
Issue number	1
DOIs	https://doi.org/10.1016/j.neuron.2010.09.006
State	Published - 6 Oct 2010

Bibliographical note

Funding Information:
We thank Laura Alexandere and Wilfredo Marin for assistance in fish maintenance and experiments. We thank Dr. Géraldine Maro for her expertise and assistance in confocal microscopy. We also thank Dr. Jamie Zeitzer and Dr. Oren levy for helping in statistical analysis and Dr. Matthew E. Carter, Dr. Brian Grone, Dr. Juliette Faraco, Dr. Simon Warby, Dr. Yoav Gothilf, and Dr. Luis de Lecea for helpful comments on the manuscript. This research was supported by the McKnight Foundation, the NIH (NS23724, NS062798), the Howard Hughes Medical Research Institute (E.M.), and the Vincent Coates Foundation (S.J.S.).

Funding

We thank Laura Alexandere and Wilfredo Marin for assistance in fish maintenance and experiments. We thank Dr. Géraldine Maro for her expertise and assistance in confocal microscopy. We also thank Dr. Jamie Zeitzer and Dr. Oren levy for helping in statistical analysis and Dr. Matthew E. Carter, Dr. Brian Grone, Dr. Juliette Faraco, Dr. Simon Warby, Dr. Yoav Gothilf, and Dr. Luis de Lecea for helpful comments on the manuscript. This research was supported by the McKnight Foundation, the NIH (NS23724, NS062798), the Howard Hughes Medical Research Institute (E.M.), and the Vincent Coates Foundation (S.J.S.).

Funders	Funder number
Howard Hughes Medical Research Institute
Vincent Coates Foundation
National Institutes of Health	P50NS023724
National Institute of Neurological Disorders and Stroke	R01NS062798
McKnight Foundation

Access to Document

10.1016/j.neuron.2010.09.006

Cite this

@article{4ba3797d286746eda444b3940aca37e6,

title = "Circadian and homeostatic regulation of structural synaptic plasticity in hypocretin neurons",

abstract = "Neurons exhibit rhythmic activity that ultimately affects behavior such as sleep. In living zebrafish larvae, we used time-lapse two-photon imaging of the presynaptic marker synaptophysin in hypocretin/orexin (HCRT) neurons to determine the dynamics of synaptic modifications during the day and night. We observed circadian rhythmicity in synapse number in HCRT axons. This rhythm is regulated primarily by the circadian clock but is also affected by sleep deprivation. Furthermore, NPTX2, a protein implicated in AMPA receptor clustering, modulates circadian synaptic changes. In zebrafish, nptx2b is a rhythmic gene that is mostly expressed in hypothalamic and pineal gland cells. Arrhythmic transgenic nptx2b overexpression (hcrt:NPTX2b) increases synapse number and abolishes rhythmicity in HCRT axons. Finally, hcrt:NPTX2b fish are resistant to the sleep-promoting effects of melatonin. This behavioral effect is consistent with NPTX2b-mediated increased activity of HCRT circuitry. These data provide real-time in vivo evidence of circadian and homeostatic regulation of structural synaptic plasticity.",

author = "Lior Appelbaum and Gordon Wang and Tohei Yokogawa and Skariah, {Gemini M.} and Smith, {Stephen J.} and Philippe Mourrain and Emmanuel Mignot",

note = "Funding Information: We thank Laura Alexandere and Wilfredo Marin for assistance in fish maintenance and experiments. We thank Dr. G{\'e}raldine Maro for her expertise and assistance in confocal microscopy. We also thank Dr. Jamie Zeitzer and Dr. Oren levy for helping in statistical analysis and Dr. Matthew E. Carter, Dr. Brian Grone, Dr. Juliette Faraco, Dr. Simon Warby, Dr. Yoav Gothilf, and Dr. Luis de Lecea for helpful comments on the manuscript. This research was supported by the McKnight Foundation, the NIH (NS23724, NS062798), the Howard Hughes Medical Research Institute (E.M.), and the Vincent Coates Foundation (S.J.S.). ",

year = "2010",

month = oct,

day = "6",

doi = "10.1016/j.neuron.2010.09.006",

language = "אנגלית",

volume = "68",

pages = "87--98",

journal = "Neuron",

issn = "0896-6273",

publisher = "Cell Press",

number = "1",

}

TY - JOUR

T1 - Circadian and homeostatic regulation of structural synaptic plasticity in hypocretin neurons

AU - Appelbaum, Lior

AU - Wang, Gordon

AU - Yokogawa, Tohei

AU - Skariah, Gemini M.

AU - Smith, Stephen J.

AU - Mourrain, Philippe

AU - Mignot, Emmanuel

N1 - Funding Information: We thank Laura Alexandere and Wilfredo Marin for assistance in fish maintenance and experiments. We thank Dr. Géraldine Maro for her expertise and assistance in confocal microscopy. We also thank Dr. Jamie Zeitzer and Dr. Oren levy for helping in statistical analysis and Dr. Matthew E. Carter, Dr. Brian Grone, Dr. Juliette Faraco, Dr. Simon Warby, Dr. Yoav Gothilf, and Dr. Luis de Lecea for helpful comments on the manuscript. This research was supported by the McKnight Foundation, the NIH (NS23724, NS062798), the Howard Hughes Medical Research Institute (E.M.), and the Vincent Coates Foundation (S.J.S.).

PY - 2010/10/6

Y1 - 2010/10/6

N2 - Neurons exhibit rhythmic activity that ultimately affects behavior such as sleep. In living zebrafish larvae, we used time-lapse two-photon imaging of the presynaptic marker synaptophysin in hypocretin/orexin (HCRT) neurons to determine the dynamics of synaptic modifications during the day and night. We observed circadian rhythmicity in synapse number in HCRT axons. This rhythm is regulated primarily by the circadian clock but is also affected by sleep deprivation. Furthermore, NPTX2, a protein implicated in AMPA receptor clustering, modulates circadian synaptic changes. In zebrafish, nptx2b is a rhythmic gene that is mostly expressed in hypothalamic and pineal gland cells. Arrhythmic transgenic nptx2b overexpression (hcrt:NPTX2b) increases synapse number and abolishes rhythmicity in HCRT axons. Finally, hcrt:NPTX2b fish are resistant to the sleep-promoting effects of melatonin. This behavioral effect is consistent with NPTX2b-mediated increased activity of HCRT circuitry. These data provide real-time in vivo evidence of circadian and homeostatic regulation of structural synaptic plasticity.

AB - Neurons exhibit rhythmic activity that ultimately affects behavior such as sleep. In living zebrafish larvae, we used time-lapse two-photon imaging of the presynaptic marker synaptophysin in hypocretin/orexin (HCRT) neurons to determine the dynamics of synaptic modifications during the day and night. We observed circadian rhythmicity in synapse number in HCRT axons. This rhythm is regulated primarily by the circadian clock but is also affected by sleep deprivation. Furthermore, NPTX2, a protein implicated in AMPA receptor clustering, modulates circadian synaptic changes. In zebrafish, nptx2b is a rhythmic gene that is mostly expressed in hypothalamic and pineal gland cells. Arrhythmic transgenic nptx2b overexpression (hcrt:NPTX2b) increases synapse number and abolishes rhythmicity in HCRT axons. Finally, hcrt:NPTX2b fish are resistant to the sleep-promoting effects of melatonin. This behavioral effect is consistent with NPTX2b-mediated increased activity of HCRT circuitry. These data provide real-time in vivo evidence of circadian and homeostatic regulation of structural synaptic plasticity.

UR - http://www.scopus.com/inward/record.url?scp=77957313794&partnerID=8YFLogxK

U2 - 10.1016/j.neuron.2010.09.006

DO - 10.1016/j.neuron.2010.09.006

M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???

C2 - 20920793

AN - SCOPUS:77957313794

SN - 0896-6273

VL - 68

SP - 87

EP - 98

JO - Neuron

JF - Neuron

IS - 1

ER -

Circadian and homeostatic regulation of structural synaptic plasticity in hypocretin neurons

Abstract

Bibliographical note

Funding

Access to Document

Other files and links

Fingerprint

Cite this