The Central Amygdala Corticotropin-releasing hormone (CRH) Neurons Modulation of Anxiety-like Behavior and Hippocampus-dependent Memory in Mice

Abstract

The encoding, consolidation and retrieval of memories is a multifaceted process that depends strongly on the optimal level of arousal but high levels of arousal may trigger anxiety, which negatively impacts the memory processing by the brain. We investigated the role of CRH neurons in the central amygdala (CeA) for their capacity to modulate both, the anxiety-like behavior and hippocampus-dependent memory. First, we activated the CRH neurons in CeA using cre-dependent AAV-DREADD in CRH-cre mice. The activation of CeA CRH neurons increased the anxiety-like behavior in Elevated-O maze (O-maze) and Light-Dark box (LDB). The activation of the CeA CRH also decreased Y-maze memory performance and the discrimination index in novel object recognition test (NOR). The inhibition of CeA CRH neurons with AAV-DREADD had the opposite effects on the anxiety-like behavior and the memory tests. Next, we used a combination of retrograde cre virus injected into locus ceruleus (LC) and cre-dependent AAV-DREADD injected into the CeA. While the excitation of the CeA neurons that project to LC increased the anxiety-like behavior, it also led to a better performance on the memory tests. The behavioral and memory effects were accompanied by increased c-Fos expression in the LC region. Pretreatment with CRH1 receptor antagonist antalarmin hydrochloride blocked the effects that were observed after the activation of the CeA projections to LC. Our findings highlight the role of CeA CRH neuronal population not only as a generator of anxiety but also demonstrate their role in the control of hippocampus-dependent memory.