Hyperlipidemia and hypertension are modifiable risk factors for cognitive decline. About 25% of adults over age 65 use both antihypertensives (AHTs) and statins to treat these conditions. Recent research in humans suggests that their combined use may delay or prevent dementia onset. However, it is not clear whether and how combination treatment may benefit brain function. To begin to address this question, we examined effects of atorvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, and Captopril, an angiotensin-converting enzyme inhibitor (ACEI), administration on memory function, anxiety-like behavior, adult hippocampal neurogenesis and angiogenesis in adult and middle-aged male C57Bl/6J mice. In adult mice (3-months-old) combination (combo) treatment, as well as administration of each compound individually, for six weeks, accelerated memory extinction in contextual fear conditioning. However, pattern separation in the touchscreen-based location discrimination test, a behavior linked to adult hippocampal neurogenesis, was unchanged. In addition, dentate gyrus (DG) neurogenesis and vascularization were unaffected. In middle-aged mice (10-months-old) combo treatment had no effect on spatial memory in the Morris water maze, but did reduce anxiety in the open field test. A potential underlying mechanism may be the modest increase in new hippocampal neurons (~20%) in the combo as compared to the control group. DG vascularization was not altered. Overall, our findings suggest that statin and anti-hypertensive treatment may serve as a potential pharmacotherapeutic approach for anxiety, in particular for post-traumatic stress disorder (PTSD) patients who have impairments in extinction of aversive memories.

Summary: The fasciola cinereum (FC) is a subregion of the hippocampus that has received relatively little research attention compared with other hippocampal subregions with respect to anatomical characteristics and functional significance. Here, we show that the FC exhibits clear anatomical borders with CA1. The FC consists of granule cells, but adult neurogenesis was not found. The FC receives inputs from the lateral entorhinal cortex and perirhinal cortex while projecting to the crest of the dentate gyrus (DG). Neurotoxic lesioning of the FC using colchicine impaired the acquisition, but not retrieval, of visual contextual memory in rats. FC lesions also impaired place recognition and object-in-place memory. Place cells in the FC showed robust place fields but fired only transiently in their fields compared with those in CA1. Our findings suggest that the FC may play critical roles in learning a novel environment by facilitating pattern separation in the DG of the hippocampus.