Sleep Promotes Downward Firing Rate Homeostasis

Pacheco, Alejandro Torrado; Bottorff, Juliet; Gao, Ya; Turrigiano, Gina G.

doi:10.1016/j.neuron.2020.11.001

Cited by 71 publications

(71 citation statements)

References 70 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…1 supplement 1 for breakdown of states). We monitored electromyograms (EMGs), EEG, and video, and used standard approaches to classify sleep states into wake and rapid eye movement (REM) or nonrapid eye movement slow wave (NREM) sleep, as described previously (Hengen et al, 2016;Torrado Pacheco et al, 2019, 2021see Methods). In some experiments we also differentiated active and quiet wake, as noted (Fig.…”

Section: Sleep/wake Behavior Of Juvenile Long Evans Ratsmentioning

confidence: 99%

Stability of neocortical synapses across sleep and wake states during the critical period in rats

Cary

Turrigiano

2021

eLife

View full text Add to dashboard Cite

Sleep is important for brain plasticity, but its exact function remains mysterious. An influential but controversial idea is that a crucial function of sleep is to drive widespread downscaling of excitatory synaptic strengths. Here we used real-time sleep classification, ex vivo measurements of postsynaptic strength, and in vivo optogenetic monitoring of thalamocortical synaptic efficacy to ask whether sleep and wake states can constitutively drive changes in synaptic strength within the neocortex of juvenile rats. We found that miniature EPSC amplitudes onto L4 and L2/3 pyramidal neurons were stable across sleep and wake dense epochs in both primary visual (V1) and prefrontal cortex (PFC). Further, chronic monitoring of thalamocortical synaptic efficacy in V1 of freely behaving animals revealed stable responses across even prolonged periods of natural sleep and wake. Together these data demonstrate that sleep does not drive widespread downscaling of synaptic strengths during the highly plastic critical period in juvenile animals. Whether this remarkable stability across sleep and wake generalizes to the fully mature nervous system remains to be seen.

show abstract

Section: Sleep/wake Behavior Of Juvenile Long Evans Ratsmentioning

confidence: 99%

Stability of neocortical synapses across sleep and wake states during the critical period in rats

Cary

Turrigiano

2021

eLife

View full text Add to dashboard Cite

show abstract

“…1A-D). We monitored electromyograms (EMGs), EEG, and video, and used standard approaches to classify sleep states into wake and rapid eye movement (REM) or non-rapid eye movement slow wave (NREM) sleep, as described previously (Hengen et al, 2016; Torrado Pacheco et al, 2019, 2020; see Methods). In some experiments we also differentiated active and quiet wake, as noted (Fig.…”

Section: Resultsmentioning

confidence: 99%

Stability of neocortical synapses across sleep and wake

Cary

Turrigiano

2019

Preprint

Self Cite

View full text Add to dashboard Cite

Sleep is widely believed to be an essential regulator of synaptic plasticity, but there is disagreement on whether it primarily enables correlation-based plasticity mechanisms such as long-term potentiation (LTP), or homeostatic forms of plasticity. Notably, it has been postulated that patterns of brain activity during sleep induce a widespread homeostatic downscaling of excitatory synaptic strengths across the brain. Here we use a combination of real-time sleep classification, ex vivo measurements of postsynaptic strength, and in vivo optogenetic monitoring of thalamocortical synapses in primary visual cortex (V1) to ask whether sleep and wake states can constitutively drive synaptic plasticity within neocortical circuits. We found that miniature EPSCs onto L4 or L2/3 pyramidal neurons were stable across sleep and wake dense epochs in both V1 and prefrontal cortex (PFC). Further, chronic monitoring of thalamocortical synaptic efficacy in V1 of freely behaving animals revealed remarkable stability of thalamocortical transmission across prolonged natural sleep and wake epochs. Together these data provide strong evidence against the view that sleep drives widespread constitutive weakening of excitatory synaptic strengths.

show abstract

“…These fluctuations in [Cl - ] i are also associated with large changes in the excitability of the network at different times of the day, consistent with the well-recognized clinical phenomenon of circadian clustering of seizures 30–33 . These data add to the growing list of diurnal fluctuations in neuronal function, including changes in firing rates 34–36 , in the number, strength and structure of synapses 37–40 , metabolic state 41 , gene expression and protein phosphorylation 42,43 . Given the direct coupling of the changes in [Cl - ] i to the biochemical state of neurons, and the well-established role of synaptic inhibition in shaping all manner of neuronal activity 44–50 , we suggest that the changes we describe here, are among the root determinants of the distinct neuronal activity patterns that constitute the cycle of brain states through the day.…”

mentioning

confidence: 76%

Diurnal variation in neuronal chloride levels and seizure susceptibility, in neocortex, reflecting changes in activity of chloride-cation-cotransporters

Pracucci

Graham

Alberio

et al. 2021

Preprint

View full text Add to dashboard Cite

The main inhibitory synaptic currents, gated by gamma-aminobutyric acid (GABA), are mediated by Cl--conducting channels1-3, and are therefore sensitive to changes in the chloride electrochemical gradient. GABAergic activity dictates the neuronal firing range4,5 and timing6-9, which in turn influences the rhythms of the brain, synaptic plasticity, and flow of information in neuronal networks7,10-12. The intracellular chloride concentration [Cl-]i 13is, therefore, ideally placed to be a regulator of neuronal activity. Chloride levels13 have been thought to be stable in adult cortical networks, except when associated with pathological activation14-17. Here, we used 2-photon LSSmClopHensor imaging14, in anaesthetized young adult mice, to show a large physiological circadian fluctuation of baseline [Cl-] inside pyramidal cells, equating to an ~15mV positive shift in ECl at times when mice are typically awake (midnight), relative to when they are usually asleep (midday). The change in pyramidal [Cl-]i alters the stability of cortical networks, as demonstrated by a greater than 3-fold longer latency to seizures induced by 4-aminopyridine at midday, compared to midnight. Importantly, both [Cl-]i and latency to seizure, in night-time experiments, were shifted in line with day-time measures, by inhibition of NKCC1. The redistribution of [Cl-]i reflects circadian changes in surface expression and phosphorylation states of the cation-chloride-co-transporters, KCC2 and NKCC1, leading to a greatly reduced chloride-extrusion capacity at night (awake period). Our data show how changes in the biochemical state of neurons may be transduced into altered brain states.

show abstract

Sleep Promotes Downward Firing Rate Homeostasis

Cited by 71 publications

References 70 publications

Stability of neocortical synapses across sleep and wake states during the critical period in rats

Stability of neocortical synapses across sleep and wake states during the critical period in rats

Stability of neocortical synapses across sleep and wake

Diurnal variation in neuronal chloride levels and seizure susceptibility, in neocortex, reflecting changes in activity of chloride-cation-cotransporters

Contact Info

Product

Resources

About