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Updated: Aug 1, 2025
Methods for the Modulation and Analysis of NF-κB-dependent Adult Neurogenesis
Published on: February 13, 2014
The p75 Neurotrophin Receptor in Preadolescent Prefrontal Parvalbumin Interneurons Promotes Cognitive Flexibility in
Pegah Chehrazi1, Karen Ka Yan Lee1, Marisol Lavertu-Jolin1
1Centre de Recherche, Centre Hospitalier Universitaire Sainte-Justine, Montréal, Canada; Department of Neurosciences, Université de Montréal, Montréal, Canada.
Background:
Parvalbumin (PV)-positive GABAergic (gamma-aminobutyric acidergic) cells provide robust perisomatic inhibition to neighboring pyramidal neurons and regulate brain oscillations. Alterations in PV interneuron connectivity and function in the medial prefrontal cortex have been consistently reported in psychiatric disorders associated with cognitive rigidity, suggesting that PV cell deficits could be a core cellular phenotype in these disorders. The p75 neurotrophin receptor (p75NTR) regulates the time course of PV cell maturation in a cell-autonomous fashion. Whether p75NTR expression during postnatal development affects adult prefrontal PV cell connectivity and cognitive function is unknown.
Methods:
We generated transgenic mice with conditional knockout of p75NTR in postnatal PV cells. We analyzed PV cell connectivity and recruitment following a tail pinch by immunolabeling and confocal imaging in naïve mice or following p75NTR re-expression in preadolescent or postadolescent mice using Cre-dependent viral vectors. Cognitive flexibility was evaluated using behavioral tests.
Results:
PV cell-specific p75NTR deletion increased both PV cell synapse density and proportion of PV cells surrounded by perineuronal nets, a marker of mature PV cells, in adult medial prefrontal cortex, but not visual cortex. Both phenotypes were rescued by viral-mediated reintroduction of p75NTR in preadolescent, but not postadolescent, medial prefrontal cortex. Prefrontal cortical PV cells failed to upregulate c-Fos following a tail-pinch stimulation in adult conditional knockout mice. Finally, conditional knockout mice showed impaired fear memory extinction learning as well as deficits in an attention set-shifting task.
Conclusions:
These findings suggest that p75NTR expression in adolescent PV cells contributes to the fine-tuning of their connectivity and promotes cognitive flexibility in adulthood.
