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.

Astrocytic signaling supports hippocampal–prefrontal theta synchronization and cognitive function

“…Within this circuit, the dorsal hippocampus performs primarily cognitive functions, while the ventral relates to emotional behavior (Fanselow & Dong, 2010). Moreover, synchrony between oscillations of hippocampal dorsal or ventral subregions, and PFC has been related respectively to cognitive (O'Neill et al, 2013) and emotional behavior (Adhikari, Topiwala, & Gordon, 2010;Kafetzopoulos et al, 2017;Mateus-Pinheiro et al, 2016;Oliveira et al, 2013). Specifically, and despite the indirect connections, O'Neill and colleagues demonstrated that dHIP theta oscillations are synchronized with theta oscillations in the mPFC, and that theta synchrony is critical for a spatial memory task.…”

Region‐specific control of microglia by adenosine A2A receptors: uncoupling anxiety and associated cognitive deficits in female rats

“…In vivo analysis of neural activity was performed as previously described, with minor changes (Mateus‐Pinheiro et al, ; Oliveira et al, ). Briefly, rats were anesthetized with 4% sevofluorane (SevoFlo, Abbott, USA) and placed in a stereotaxic frame (KOPF, USA) once they were deeply anesthetized.…”

Functional polymorphisms and transcriptional analysis in the 5' region of the human serotonin receptor 1B gene (HTR1B) and their associations with psychiatric disorders

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