title: AP2γ controls adult hippocampal neurogenesis and modulates cognitive, but not anxiety or depressive-like behavior.
abstract: 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.
authors: Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal.|Life and Health Sciences Research Institute (ICVS)/3B's-PT Government Associate Laboratory, Guimarães, Portugal.
authors: A
authors: A
authors: Mateus-Pinheiro
authors: Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal.|Life and Health Sciences Research Institute (ICVS)/3B's-PT Government Associate Laboratory, Guimarães, Portugal.
authors: N D
authors: ND
authors: Alves
authors: Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal.|Life and Health Sciences Research Institute (ICVS)/3B's-PT Government Associate Laboratory, Guimarães, Portugal.
authors: P
authors: P
authors: Patrício
authors: Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal.|Life and Health Sciences Research Institute (ICVS)/3B's-PT Government Associate Laboratory, Guimarães, Portugal.
authors: A R
authors: AR
authors: Machado-Santos
authors: Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal.|Life and Health Sciences Research Institute (ICVS)/3B's-PT Government Associate Laboratory, Guimarães, Portugal.
authors: E
authors: E
authors: Loureiro-Campos
authors: Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal.|Life and Health Sciences Research Institute (ICVS)/3B's-PT Government Associate Laboratory, Guimarães, Portugal.
authors: J M
authors: JM
authors: Silva
authors: Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal.|Life and Health Sciences Research Institute (ICVS)/3B's-PT Government Associate Laboratory, Guimarães, Portugal.
authors: V M
authors: VM
authors: Sardinha
authors: Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal.|Life and Health Sciences Research Institute (ICVS)/3B's-PT Government Associate Laboratory, Guimarães, Portugal.
authors: J
authors: J
authors: Reis
authors: Department of Developmental Pathology, Institute for Pathology, University of Bonn Medical School, Bonn, Germany.
authors: H
authors: H
authors: Schorle
authors: Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal.|Life and Health Sciences Research Institute (ICVS)/3B's-PT Government Associate Laboratory, Guimarães, Portugal.
authors: J F
authors: JF
authors: Oliveira
authors: Institute for Stem Cell Research, Helmholtz Centre Munich German Research Center for Environmental Health (GmbH), Neuherberg, Germany.|Physiological Genomics, Medical Faculty, University of Munich, Munich, Germany.
authors: J
authors: J
authors: Ninkovic
authors: Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal.|Life and Health Sciences Research Institute (ICVS)/3B's-PT Government Associate Laboratory, Guimarães, Portugal.
authors: N
authors: N
authors: Sousa
authors: Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal.|Life and Health Sciences Research Institute (ICVS)/3B's-PT Government Associate Laboratory, Guimarães, Portugal.
authors: L
authors: L
authors: Pinto
mesh_terms: D000818:Animals; D001007:Anxiety / Q000378:metabolism* / Q000473:pathology; D049109:Cell Proliferation / Q000502:physiology; D003071:Cognition / Q000502:physiology*; D004268:DNA-Binding Proteins; D003863:Depression / Q000378:metabolism* / Q000473:pathology; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism*; D007858:Learning / Q000502:physiology; D008297:Male; D008568:Memory / Q000502:physiology; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000378:metabolism; D055495:Neurogenesis / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D017397:Prefrontal Cortex / Q000166:cytology / Q000378:metabolism; D055153:Stem Cell Niche / Q000502:physiology; D020825:T-Box Domain Proteins / Q000378:metabolism; D050656:Transcription Factor AP-2 / Q000235:genetics / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; C491198:Eomes protein, mouse; D009419:Nerve Tissue Proteins; C492380:NeuN protein, mouse; D009687:Nuclear Proteins; D020825:T-Box Domain Proteins; C583890:Tfap2c protein, mouse; D050656:Transcription Factor AP-2