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Mateus-Pinheiro, A.* ; Alves, N.D.* ; Patrício, P.* ; Machado-Santos, A.R.* ; Loureiro-Campos, E.* ; Silva, J.* ; Sardinha, V.M.* ; Reis, J.* ; Schorle, H.* ; Oliveira, J.F.* ; Ninkovic, J. ; Sousa, N.* ; Pinto, L.*

AP2γ controls adult hippocampal neurogenesis and modulates cognitive, but not anxiety or depressive-like behavior.

Mol. Psychiatry 22, 1725-1734 (2016)
Open Access Green as soon as Postprint is submitted to ZB.
Hippocampal neurogenesis has been proposed to participate in a myriad of behavioral responses, both in basal states and in the context of neuropsychiatric disorders. Here, we identify activating protein 2γ (AP2γ, also known as Tcfap2c), originally described to regulate the generation of neurons in the developing cortex, as a modulator of adult hippocampal glutamatergic neurogenesis in mice. Specifically, AP2γ is present in a sub-population of hippocampal transient amplifying progenitors. There, it is found to act as a positive regulator of the cell fate determinants Tbr2 and NeuroD, promoting proliferation and differentiation of new glutamatergic granular neurons. Conditional ablation of AP2γ in the adult brain significantly reduced hippocampal neurogenesis and disrupted neural coherence between the ventral hippocampus and the medial prefrontal cortex. Furthermore, it resulted in the precipitation of multimodal cognitive deficits. This indicates that the sub-population of AP2γ-positive hippocampal progenitors may constitute an important cellular substrate for hippocampal-dependent cognitive functions. Concurrently, AP2γ deletion produced significant impairments in contextual memory and reversal learning. More so, in a water maze reference memory task a delay in the transition to cognitive strategies relying on hippocampal function integrity was observed. Interestingly, anxiety- and depressive-like behaviors were not significantly affected. Altogether, findings open new perspectives in understanding the role of specific sub-populations of newborn neurons in the (patho)physiology of neuropsychiatric disorders affecting hippocampal neuroplasticity and cognitive function in the adult brain.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Neural Stem-cells; Olfactory-bulb Interneurons; Dentate Granule Cells; Prefrontal Cortex; Radial Glia; Neuronal Differentiation; Intermediate Progenitors; Phase Synchronization; Ventral Hippocampus; Mammalian Brain
ISSN (print) / ISBN 1359-4184
e-ISSN 1476-5578
Quellenangaben Volume: 22, Issue: 12, Pages: 1725-1734 Article Number: , Supplement: ,
Publisher Nature Publishing Group
Publishing Place London
Reviewing status Peer reviewed