Abstract
The transcription factor activating protein two gamma (AP2γ) is an important regulator of neurogenesis both during embryonic development as well as in the postnatal brain, but its role for neurophysiology and behavior at distinct postnatal periods is still unclear. In this work, we explored the neurogenic, behavioral, and functional impact of a constitutive and heterozygous AP2γ deletion in mice from early postnatal development until adulthood. AP2γ deficiency promotes downregulation of hippocampal glutamatergic neurogenesis, altering the ontogeny of emotional and memory behaviors associated with hippocampus formation. The impairments induced by AP2γ constitutive deletion since early development leads to an anxious-like phenotype and memory impairments as early as the juvenile phase. These behavioral impairments either persist from the juvenile phase to adulthood or emerge in adult mice with deficits in behavioral flexibility and object location recognition. Collectively, we observed a progressive and cumulative impact of constitutive AP2γ deficiency on the hippocampal glutamatergic neurogenic process, as well as alterations on limbic-cortical connectivity, together with functional behavioral impairments. The results herein presented demonstrate the modulatory role exerted by the AP2γ transcription factor and the relevance of hippocampal neurogenesis in the development of emotional states and memory processes.
Highlights
New cells are continuously generated, differentiated into neurons, and integrated into the preexisting neural networks in restricted regions of the postnatal mouse brain (Dennis et al., 2016; Kempermann et al, 2018; Moreno-Jiménez et al, 2019; Tobin et al, 2019)
The electrophysiological studies revealed that AP2 constitutive and heterozygous deficiency led to two outcomes: first, a significant decrease of coherence between the dorsal hippocampus (dHip) and the medial prefrontal cortex (mPFC) indicating impairments in the ability of these regions to functionally interact; second, this decrease in interregional coherence was accompanied by a diminished neuronal activity in a range of frequencies in the mPFC, including in theta and beta frequencies, previously shown to be critically related with behavioral outputs dependent on cortico-limbic networks (Colgin, 2011; Fell and Axmacher, 2011; Oliveira et al, 2013)
Discussion: we show that despite a normal early postnatal acquisition of neurodevelopmental milestones, AP2 constitutive and heterozygous deficiency causes emotional and memory deficits in juvenile mice that persist into adulthood, while behavioral flexibility and object location recognition impairments emerge only in adult mice
Summary
New cells are continuously generated, differentiated into neurons, and integrated into the preexisting neural networks in restricted regions of the postnatal mouse brain (Dennis et al., 2016; Kempermann et al, 2018; Moreno-Jiménez et al, 2019; Tobin et al, 2019). The ontogenetic interpretation of hippocampal neurogenesis assigns different functional relevance to DHN as the neurogenic process that establishes the basic repertoire of adaptable behaviors and AHN as the neurogenic process that underpins the adult brain's ability to adapt functional behaviors (Abrous et al, 2021; Masachs et al, 2021; Tronel et al, 2015) This functional dissociation between these two stages of hippocampal neurogenesis allows us to understand how influences in the neurogenic process at different phases can lead to distinct impairments in emotional states and cognitive functions. Mice with conditional deletion of AP2 exhibit behavioral impairments, a deficient performance in cognitive-related tasks (Mateus-Pinheiro et al, 2018, 2017) These studies reveal the crucial modulatory role of AP2 during embryonic cerebral cortex development as well as its influence on glutamatergic neurogenesis and hippocampal-dependent behaviors during adulthood. These functional behavioral impairments are either maintained from the juvenile phase to adulthood or emerge as behavioral flexibility and object location recognition deficits in adult mice with AP2 constitutive deletion
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
