The price of being awake and the function of sleep: synaptic homeostasis
Monday 10 December, 4pm at the Large Lecture Theatre, DPAG/Le Gros Clark Bldg
The Cortex Club is delighted to co-host, together with the CNCB, Prof Chiara Cirelli from the University of Wisconsin-Madison, who will be talking to us about her research on synaptic homeostastis during sleep. Please join us on December 10th at the Large Lecture Theatre, located in the Le Gros Clark Building of the Department of Physiology, Anatomy and Genetics.
Prof. Chiara Cirelli has kindly agreed to meet students and staff individually. If you would like to arrange a meeting please contact Fiona Woods (fiona.woods – at – cncb.ox.ac.uk).
To join us in the pub after the talk – where we’ll be joined by both Prof Cirelli and Prof Tononi – please register at https://goo.gl/forms/yxneVL15Nxs3YIDG3
Sleep is universal, tightly regulated, and many cognitive functions are impaired if we do not sleep. But
why? Any hypothesis about the essential function of sleep must take into account that when asleep we
are essentially offline: sensory disconnection must be crucial for whatever function sleep serves. If not,
natural selection would likely have found a way to perform the same function while awake, avoiding
the danger of being unable to monitor the environment.
Over the past 20 years, we have developed and tested a comprehensive hypothesis about the core
function of sleep: The Synaptic Homeostasis Hypothesis (SHY). SHY states that sleep is the price we pay
for brain plasticity. During wakefulness the excitatory synapses that allow neurons to communicate
with each other undergo net potentiation as a result of learning, an ongoing process that happens all the
time while we are awake, constantly adapting to an ever-changing environment. The plasticity of the
brain is essential for survival but is also a costly process, because stronger synapses increase the
demand for energy and cellular supplies, lead to decreases in signal-to-noise ratios, and saturate the
ability to learn. According to SHY, the renormalization of synaptic strength should mainly occur
during sleep when the brain is disconnected from the environment and neural circuits can be broadly
reactivated off-line to undergo a systematic and yet specific synaptic down-selection. This
renormalization favors memory consolidation and the integration of new with old memories, and
eliminates the synapses that contribute more to the “noise” than to the “signal.” Just as crucially,
synaptic renormalization during sleep restores the homeostasis of energy and cellular supplies,
including many proteins and lipids that are part of the synapses, with beneficial effects at both the
systems and cellular level.
I will discuss the rationale underlying this hypothesis and summarize electrophysiological, molecular
and ultrastructural studies in flies, rodents and humans that confirmed SHY’s main predictions,
including the recent observation, obtained using serial block face scanning electron microscopy, that
most synapses in mouse primary motor and sensory cortices grow after wake and shrink after sleep. I
will then present unpublished ultrastructural data obtained in the hippocampus and in the cortex of
mouse pups. Finally, I will examine recent studies by other groups showing the causal role of cortical
slow waves and hippocampal ripples in sleep-dependent synaptic down-selection, and some of the
molecular mechanisms that can mediate this process.