Synaptic refinement during development and its effect on slow-wave activity: a computational study
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Recent evidence suggests that synaptic refinement, the reorganization of synapses and connections without significant change in their number or strength, is important for the development of the visual system of juvenile rodents. Other evidence in rodents and humans shows that there is a marked drop in sleep slow-wave activity (SWA) during adolescence. Slow waves reflect synchronous transitions of neuronal populations between active and inactive states, and the amount of SWA is influenced by the connection strength and organization of cortical neurons. In this study, we investigated whether synaptic refinement could account for the observed developmental drop in SWA. To this end, we employed a large-scale neural model of primary visual cortex and sections of the thalamus, capable of producing realistic slow waves. In this model, we reorganized intralaminar connections according to experimental data on synaptic refinement: during prerefinement, local connections between neurons were homogenous, whereas in postrefinement, neurons connected preferentially to neurons with similar receptive fields and preferred orientations. Synaptic refinement led to a drop in SWA and to changes in slow-wave morphology, consistent with experimental data. To test whether learning can induce synaptic refinement, intralaminar connections were equipped with spike timing-dependent plasticity. Oriented stimuli were presented during a learning period, followed by homeostatic synaptic renormalization. This led to activity-dependent refinement accompanied again by a decline in SWA. Together, these modeling results show that synaptic refinement can account for developmental changes in SWA. Thus sleep SWA may be used to track noninvasively the reorganization of cortical connections during development.
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Other neurodevelopmental disorders, such as PWS and SMS, are linked more directly to dysfunctional circadian rhythm pathways.
“Other neurodevelopmental disorders, such as PWS and SMS, are linked more directly to dysfunctional circadian rhythm pathways107,108.”
From Rhythms of life: circadian disruption and brain disorders across the lifespan (2019) · cites this paper as [107]
These developmental changes include increases in synaptic pruning and myelination, as well as increases in the availability of dopamine in the limbic circuitry.
“These changes include increases in synaptic pruning and myelination107,171, as well as increases in the availability of dopamine in the limbic circuitry172,173.”
From Rhythms of life: circadian disruption and brain disorders across the lifespan (2019) · cites this paper as [107]
Insults during adolescence that affect sleep and circadian stability may contribute to the pathophysiology underlying the vulnerability and progression of these diseases later in life.
“insults during adolescence that affect sleep and circadian stability may contribute to the pathophysiology underlying the vulnerability and progression of these diseases later in life107,108”
From Rhythms of life: circadian disruption and brain disorders across the lifespan (2019) · cites this paper as [107]
The reduction in slow-wave activity during adolescence is suggested to result directly from synaptic refinement.
“this reduction is suggested to result directly from synaptic refinement”
From Rhythms of life: circadian disruption and brain disorders across the lifespan (2019) · cites this paper as [107]
Slow-wave activity during sleep dramatically decreases specifically during adolescence.
“slow-wave activity during sleep dramatically decreases specifically during adolescence”
From Rhythms of life: circadian disruption and brain disorders across the lifespan (2019) · cites this paper as [107]
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References 69 · Cited by 30
- Authors
- Hoel, E. P., Albantakis, L., Cirelli, C., & Tononi, G.
- Affiliations
- University of Wisconsin–Madison (US)
- Corresponding author
- Tononi, Giulio
- Venue
- Journal of Neurophysiology
- Publisher
- American Physiological Society
- Published
- 2016-04-01
- Volume
- 115
- Issue
- 4
- Pages
- 2199-2213
- ISSN
- 0022-3077 (ISSN-L)
- 1522-1598
- PMC
- PMC4869496
- OpenAlex
- W2254222810
- Cited by
- 30
- References
- 69
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 2 · 2023: 1 · 2022: 2 · 2021: 2 · 2020: 5 · 2019: 5 · 2018: 5 · 2017: 4 · 2016: 1
- FWCI
- 3.18
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Neurophysiology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5p01ns083514-05)
- National Institute of Mental Health (R01MH099231)
- National Institute of General Medical Sciences (T32GM007507)
- National Institute of Neurological Disorders and Stroke (P01 NS-083514)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
- Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- synaptic refinement, slow-wave activity, sleep, primary visual cortex, thalamus, cortical development, adolescence, spike-timing-dependent plasticity, crystallographic texture, computational neural model, visual system development
- MeSH terms
- Animals, Humans, Models, Neurological, Neurons, Sleep, Thalamus, Visual Cortex, Synaptic Potentials, Neurogenesis, Brain Waves
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