Lizbeth Ramos, Abigail E Harr, Finian L Zakas, Samuel R Essig, Griffen J Kempskie, Nelly A Fadil, Makayla G Schmid, Madison D Pompy, Michael C Curley, Lisa A Gabel, Henry L Hallock
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引用次数: 0
Abstract
Apolipoprotein E (ApoE) is a protein that is important for lipid storage, transport, and metabolism. APOE gene variants are associated with Alzheimer's disease, as well as attentional function in healthy humans. Previous research has shown that Apoe transcription is increased following stimulation of the pathway between the locus coeruleus (LC) and frontal cortex (FC) in mice. This result suggests that Apoe may affect attentional function by virtue of its expression in circuits that control attention. Does Apoe causally regulate attention, or is its expression simply a byproduct of neuronal activity in the LC and FC? To answer this question, we synthetically induced Apoe transcription in the FC of male and female mice, and subsequently tested their ability to learn a touchscreen-based rodent version of the continuous performance test of sustained attention (the rCPT). We found that increased Apoe transcription impaired performance when attentional demand was increased in male mice, while in female mice, increased Apoe transcription significantly accelerated rCPT learning. We further found that this increase in Apoe transcription affected one metric of the open field test, as well as cellular activity in the FC in a sex-dependent manner. The results of this study provide insight into how Apoe causally regulates translationally relevant behaviors in rodent models.
期刊介绍:
The neurobiology of learning and memory is entering a new interdisciplinary era. Advances in neuropsychology have identified regions of brain tissue that are critical for certain types of function. Electrophysiological techniques have revealed behavioral correlates of neuronal activity. Studies of synaptic plasticity suggest that some mechanisms of memory formation may resemble those of neural development. And molecular approaches have identified genes with patterns of expression that influence behavior. It is clear that future progress depends on interdisciplinary investigations. The current literature of learning and memory is large but fragmented. Until now, there has been no single journal devoted to this area of study and no dominant journal that demands attention by serious workers in the area, regardless of specialty. Learning & Memory provides a forum for these investigations in the form of research papers and review articles.