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

Center for Narcolepsy, Department of Psychiatry and Behavioral Sciences, Stanford University, Palo Alto, California 94305, USA. liora@mail.biu.ac.i

Neuron 2010 Oct 6

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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. Copyright © 2010 Elsevier Inc. All rights reserved.

Citation

Lior Appelbaum, Gordon Wang, Tohei Yokogawa, Gemini M Skariah, Stephen J Smith, Philippe Mourrain, Emmanuel Mignot. Circadian and homeostatic regulation of structural synaptic plasticity in hypocretin neurons. Neuron. 2010 Oct 6;68(1):87-98