Reduction in cortical parvalbumin expression due to intermittent theta-burst stimulation correlates with maturation of the perineuronal nets in young rats
Abstract
We recently showed that intermittent theta-burst stimulation (iTBS) using transcranial magnetic stimulation strongly reduces the number of rat neocortical interneurons expressing glutamic acid decarboxylase 67 kDa (GAD67) and parvalbumin (PV), indicating changed activity of fast-spiking (FS) interneurons. In advance of in vitro studies intended to characterize changes in electrical properties of FS interneurons under these conditions, we tested whether the iTBS effect is age-dependent. Conscious Sprague-Dawley rats aged between 28 and 90 days received three blocks of iTBS at 15 min intervals. We found that iTBS-related reduction in PV+ cells was absent up to an age of 32 days, then gradually increased, and approached a maximum of about 40% reduction at an age of about 40 days. The relative number of cells expressing PV (PV+, 8-9%) did not change with age in sham-controls and also the increase in cortical c-Fos expression induced by iTBS was not principally age-dependent. However, a prominent growth of the perineuronal nets, typically surrounding the PV+ cells, exactly paralleled the increase in the iTBS effect. Based on these findings, we conclude that the functional development of the inhibitory network of PV+ interneurons with regard to intracortical synaptic connectivity is not sufficiently matured in rats younger than 35 d to enable activity-dependent modifications during iTBS. Outgrowth of the perineuronal nets and associated maturation of excitatory cortical inputs, as is characteristic for the critical cortical period, may take place before PV+ interneurons can be sufficiently activated via repetitive transcranial magnetic stimulation, allowing plastic changes of molecular phenotype and likely also synaptic plasticity.
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Experimentally induced theta bursts reduce PV expression in other brain regions.
“Along these lines, it is worth noting that experimentally induced theta bursts reduce PV expression in other brain regions (70; 71), raising the possibility that the changes we observed in PV intensity are the result of, as opposed to being responsible for, the altered electrophysiological profile observed with MSEW.”
From Perineuronal nets, inhibitory interneurons and anxiety-related ventral hippocampal neuronal oscillations are altered by early life adversity (2019) · cites this paper as [70]
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Ten years of theta burst stimulation in humans: Established knowledge, unknowns and prospects
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- Authors
- Mix, A., Hoppenrath, K., & Funke, K.
- Affiliations
- Ruhr University Bochum (DE)
- Corresponding author
- Funke, Klaus
- ORCID
- Funke, Klaus
- Venue
- Developmental Neurobiology
- Publisher
- Wiley
- Published
- 2014-06-26
- Volume
- 75
- Issue
- 1
- Pages
- 1-11
- ISSN
- 1932-8451 (ISSN-L)
- 1932-846X
- OpenAlex
- W1546926080
- Cited by
- 48
- References
- 47
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 1 · 2023: 3 · 2022: 8 · 2021: 6 · 2020: 4 · 2019: 3 · 2018: 7 · 2017: 4 · 2016: 5 · 2015: 3 · 2014: 1
- FWCI
- 2.26
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Developmental Neurobiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- German Science Foundation (DFG) (SFB 874 TP A4)
- Topics
- Life Sciences › Neuroscience › Neurology › Transcranial Magnetic Stimulation Studies
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
- Keywords
- intermittent theta burst stimulation, parvalbumin, perineuronal nets, fast-spiking interneurons, cortical development, age-dependent plasticity, GAD67, c-fos, critical period, synaptic plasticity, transcranial magnetic stimulation
- MeSH terms
- Age Factors, Animals, Cerebral Cortex, Interneurons, Male, Neural Inhibition, Neuronal Plasticity, Parvalbumins, Theta Rhythm, Rats, Sprague-Dawley, Transcranial Magnetic Stimulation, Rats
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