Jens Randel Nyengaard

Layers II/III of Prefrontal Cortex in Df(h22q11)/+ Mouse Model of the 22q11.2 Deletion Display Loss of Parvalbumin Interneurons and Modulation of Neuronal Morphology and Excitability

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

  • Abdel-Rahman Al-Absi
  • Per Qvist, iPSYCH -The Lundbeck Foundation Initiative for Integrative Psychiatric Research
  • ,
  • Samora Okujeni, University of Freiburg/Universtiy Children's Hospital Freiburg, Freiburg, Germany.
  • ,
  • Ahmad Raza Khan, Centre of Biomedical Research (CBMR)
  • ,
  • Simon Glerup
  • Connie Sanchez
  • ,
  • Jens R Nyengaard

The 22q11.2 deletion has been identified as a risk factor for multiple neurodevelopmental disorders. Behavioral and cognitive impairments are common among carriers of the 22q11.2 deletion. Parvalbumin expressing (PV+) interneurons provide perisomatic inhibition of excitatory neuronal circuits through GABAA receptors, and a deficit of PV+ inhibitory circuits may underlie a multitude of the behavioral and functional deficits in the 22q11.2 deletion syndrome. We investigated putative deficits of PV+ inhibitory circuits and the associated molecular, morphological, and functional alterations in the prefrontal cortex (PFC) of the Df(h22q11)/+ mouse model of the 22q11.2 hemizygous deletion. We detected a significant decrease in the number of PV+ interneurons in layers II/III of PFC in Df(h22q11)/+ mice together with a reduction in the mRNA and protein levels of GABAA (α3), a PV+ putative postsynaptic receptor subunit. Pyramidal neurons from the same layers further experienced morphological reorganizations of spines and dendrites. Accordingly, a decrease in the levels of the postsynaptic density protein 95 (PSD95) and a higher neuronal activity in response to the GABAA antagonist bicuculline were measured in these layers in PFC of Df(h22q11)/+ mice compared with their wild-type littermates. Our study shows that a hemizygotic deletion of the 22q11.2 locus leads to deficit in the GABAergic control of network activity and involves molecular and morphological changes in both the inhibitory and excitatory synapses of parvalbumin interneurons and pyramidal neurons specifically in layers II/III PFC.

Original languageEnglish
JournalMolecular Neurobiology
Pages (from-to)4978–4988
Number of pages11
Publication statusPublished - Dec 2020

    Research areas

  • CELLS, DEFICITS, DENSITY, DYSFUNCTION, Df(h22q11)/+mouse model, EXPRESSION, GABA(A)(alpha 3) receptor subunit, PROFILE, PYRAMIDAL NEURONS, Parvalbumin interneurons, Prefrontal cortex, Pyramidal neurons, SCHIZOPHRENIA

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