Brain connections have rhythm: Circadian and Homeostatic Regulation of Structural Synaptic Plasticity in Hypocretin Neurons @ STANFORD


Circadian and Homeostatic Regulation of Structural Synaptic Plasticity in Hypocretin Neurons

Lior Appelbaum1, 2, 6, 7, Corresponding Author Contact Information, E-mail The Corresponding Author, Gordon Wang3, 7, Tohei Yokogawa1, 2, 4, Gemini M. Skariah1, Stephen J. Smith3, Philippe Mourrain1, 5, 8, Corresponding Author Contact Information, E-mail The Corresponding Author and Emmanuel Mignot1, 2, 8

1 Center for Narcolepsy, Department of Psychiatry and Behavioral Sciences, Stanford University, Palo Alto, California, 94305, USA
2 Howard Hughes Medical Institute, Stanford University, Palo Alto, California, 94305, USA
3 Department of Molecular and Cellular Physiology, Beckman Center, Stanford University, Palo Alto, California 94305, USA
4 Laboratory of Molecular Genetics, NICHD, NIH, Bethesda, Maryland 20892, USA
5 INSERM, U784, Paris, F-75005, France

Summary

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.

Neuroscience: Brain connections have rhythm

Circadian and Homeostatic Regulation of Structural Synaptic Plasticity in Hypocretin Neurons

The number of neuron-to-neuron connections, or synapses, that an animal has is thought to vary from one time of day to another. A team of scientists at Stanford University in California set out to watch the process in live zebrafish larvae, using time-lapse fluorescence microscopy.

Lior Appelbaum, currently at Bar-Ilan University in Ramat Gan, Israel, and his colleagues followed the creation and disappearance of synapses over a 24-hour period. They focused on a particular class of neuron in two brain areas known to be involved in regulating sleeping and waking: the pineal gland and the hindbrain.

The authors showed that the number of synapses fluctuated rhythmically between day and night. They also found that a protein, Nptx2, for which levels in the brain also vary rhythmically during the 24-hour period, is involved in regulating the rhythmicity of synapse number.

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