Brain‐derived neurotrophic factor haploinsufficiency impairs high‐frequency cortical oscillations in mice
Open accessAbstract
Schizophrenia is a complex psychiatric disorder with a heterogeneous aetiology involving genetic and environmental factors. Deficiencies in both brain‐derived neurotrophic factor (BDNF) and NMDA receptor function have been implicated in the disorder and may play causal and synergistic roles. Perturbations in the regulation of electrophysiological signals, including high‐frequency (γ: 30–80 Hz and β: 20–30 Hz) neuronal oscillations, are also associated with the disorder. This study investigated the influence of BDNF deficiency and NMDA receptor hypofunction on electrophysiological responses to brief acoustic stimuli. Adult BDNF heterozygote (BDNF+/−) and wild‐type littermate C57Bl/6J mice were surgically implanted with EEG recording electrodes. All mice underwent EEG recording sessions to measure ongoing and auditory‐evoked electrophysiological responses following treatment with MK‐801 (0.3 mg/kg ip) or vehicle. Western blotting on post‐mortem cortical tissue assessed parvalbumin and GAD 67 expression – markers of interneurons which are involved in the generation of gamma oscillations. Compared with wild‐type controls, BDNF+/− mice exhibited markedly dampened electrophysiological responses to auditory stimuli, including reductions in the amplitude of multiple components of the event‐related potential and auditory‐evoked oscillations, as well as reduced ongoing cortical gamma oscillations. MK‐801 elevated ongoing gamma power but suppressed evoked gamma power, and this was observed equally across genotypes. BDNF+/− mice also displayed reductions in parvalbumin, but not GAD 67 expression. We conclude that reduced BDNF expression leads to impairments in the generation of high‐frequency neural oscillations, but this is not synergistic with NMDA receptor hypofunction. Reduced parvalbumin expression associated with BDNF haploinsufficiency may provide a molecular explanation for these electrophysiological deficits.
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Mouse models relevant to both schizophrenia and bipolar disorder, including Disc1 and Bdnf models, show abnormal PV-IN function ranging from migration deficits to reduced interneuron number.
“Mouse models relevant for both disorders, including the disrupted in schizophrenia 1 gene (Disc1) [57][58][59][60][61], or brain derived neurotrophic factor (Bdnf) [62], show abnormal PV-IN function ranging from migration deficits to reduction in IN number.”
From Parvalbumin interneuron vulnerability and brain disorders (2021) · cites this paper as [62]
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Research works printed but not linked: 2
- Rickman, D.W. (1999) Parvalbumin immunoreactivity is enhanced by brain-derived neurotrophic factor in organotypic cultures of rat retina. Journal of neurobiology, 41, 376-384.
- Jones, N. C., Hudson, M., Foreman, J., Rind, G., Hill, R., Manning, E. E. & van den Buuse, M. (2018). Brain-derived neurotrophic factor haploinsufficiency impairs high- frequency cortical oscillations in mice. EUROPEAN JOURNAL OF NEUROSCIENCE, 48 (8), pp.2816-2825. https://doi.org/10.1111/ejn.13722. Persistent Link: http://hdl.handle.net/11343/293829
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Parvalbumin interneuron vulnerability and brain disorders
Ruden, J. B., Dugan, L. L., & Konradi, C. (2021) · Neuropsychopharmacology · doi:10.1038/s41386-020-0778-9 · Cited by 194 · see citing works
- Authors
- Jones, N. C., Hudson, M., Foreman, J., Rind, G., Hill, R., Manning, E. E., & van den Buuse, M.
- Affiliations
- The Royal Melbourne Hospital (AU)
- The University of Melbourne (AU)
- Melbourne Brain Centre Florey Institutes of Neuroscience and Mental Health University of Melbourne Parkville Vic. Australia
- Corresponding author
- Jones, Nigel C.
- Venue
- European Journal of Neuroscience
- Publisher
- Wiley
- Published
- 2017-11-06
- Volume
- 48
- Issue
- 8
- Pages
- 2816-2825
- ISSN
- 0953-816X (ISSN-L)
- 1460-9568
- OpenAlex
- W2754767755
- Cited by
- 20
- References
- 54
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 2 · 2022: 1 · 2020: 6 · 2019: 6 · 2018: 1
- FWCI
- 2.92
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- European Journal of Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- ResearchOnline - JCU (James Cook University) (submittedVersion)
- Minerva Access (University of Melbourne) (submittedVersion)
- Funders
- Australian Research Council (1059860, MvdB ‐ 1044777)
- National Health and Medical Research Council
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
- Keywords
- brain-derived neurotrophic factor, schizophrenia, gamma oscillations, beta oscillations, NMDA receptor hypofunction, MK-801, auditory evoked potentials, parvalbumin, GAD67, interneurons
- MeSH terms
- Animals, Male, Mice, Inbred C57BL, Mice, Transgenic, Prefrontal Cortex, Brain-Derived Neurotrophic Factor, Mice, Haploinsufficiency, Brain Waves
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