Prolonged deficits in parvalbumin neuron stimulation-evoked network activity despite recovery of dendritic structure and excitability in the somatosensory cortex following global ischemia in mice.
Open accessAbstract
Relatively few studies have examined plasticity of inhibitory neuronal networks following stroke in vivo, primarily due to the inability to selectively monitor inhibition. We assessed the structure of parvalbumin (PV) interneurons during a 5 min period of global ischemia and reperfusion in mice, which mimicked cerebral ischemia during cardiac arrest or forms of transient ischemic attack. The dendritic structure of PV-neurons in cortical superficial layers was rapidly swollen and beaded during global ischemia, but recovered within 5–10 min following reperfusion. Using optogenetics and a multichannel optrode, we investigated the function of PV-neurons in mouse forelimb somatosensory cortex. We demonstrated pharmacologically that PV-channelrhodopsin-2 (ChR2) stimulation evoked activation in layer IV/V, which resulted in rapid current sinks mediated by photocurrent and action potentials (a measure of PV-neuron excitability), which was then followed by current sources mediated by network GABAergic synaptic activity. During ischemic depolarization, the PV-ChR2-evoked current sinks (excitability) were suppressed, but recovered rapidly following reperfusion concurrent with repolarization of the DC-EEG. In contrast, the current sources reflecting GABAergic synaptic network activity recovered slowly and incompletely, and was coincident with the partial recovery of the forepaw stimulation-evoked current sinks in layer IV/V 30 min post reperfusion. Our in vivo data suggest that the excitability of PV inhibitory neurons was suppressed during global ischemia and rapidly recovered during reperfusion. In contrast, PV-ChR2 stimulation-evoked GABAergic synaptic network activity exhibited a prolonged suppression even ∼1 h after reperfusion, which could contribute to the dysfunction of sensation and cognition following transient global ischemia.
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Reduced PV-immunoreactivity and PV cell function have been observed following stroke.
“reduced PV-immunoreactivity and PV cell function have also been observed following stroke”
From The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders (2018) · cites this paper as Xie et al., 2014
Decrease in inhibitory cell function may underlie epilepsy-like activity following stroke.
“this decrease in inhibitory cell function may underlie epilepsy-like activity following stroke (Hobohm et al., 2005; Xie et al., 2014).”
From The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders (2018) · cites this paper as Xie et al., 2014
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The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders
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- Authors
- Xie, Y., Chen, S., Wu, Y., & Murphy, T. H.
- Affiliations
- University of British Columbia (CA)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2014-11-05
- Volume
- 34
- Issue
- 45
- Pages
- 14890-14900
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6608365
- OpenAlex
- W2011324056
- Cited by
- 35
- References
- 81
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 2 · 2022: 6 · 2021: 2 · 2020: 2 · 2019: 2 · 2018: 4 · 2017: 5 · 2016: 2 · 2015: 4
- FWCI
- 1.68
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Heart and Stroke Foundation of Canada
- Allen Institute for Artificial Intelligence
- University of British Columbia
- Canadian Institutes of Health Research (111009_1)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
- Health Sciences › Medicine › Psychiatry and Mental health › Epilepsy research and treatment
- Keywords
- parvalbumin interneurons, global cerebral ischemia, ischemia-reperfusion, somatosensory cortex, dendritic swelling, neuronal excitability, stroke, transient ischemic attack
- MeSH terms
- Channelrhodopsins, Action Potentials, Animals, Cerebral Infarction, Dendrites, Interneurons, Mice, Inbred C57BL, Parvalbumins, Somatosensory Cortex, Mice, Inhibitory Postsynaptic Potentials, GABAergic Neurons, Optogenetics
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