Abstract
Alterations in prefrontal cortex (PFC) function and abnormalities in its interactions with other brain areas (i.e., the hippocampus) have been related to Alzheimer Disease (AD). Considering that these malfunctions correlate with the increase in the brain's amyloid beta (Aβ) peptide production, here we looked for a causal relationship between these pathognomonic signs of AD. Thus, we tested whether or not Aβ affects the activity of the PFC network and the activation of this cortex by hippocampal input stimulation in vitro. We found that Aβ application to brain slices inhibits PFC spontaneous network activity as well as PFC activation, both at the population and at the single-cell level, when the hippocampal input is stimulated. Our data suggest that Aβ can contribute to AD by disrupting PFC activity and its long-range interactions throughout the brain.
Highlights
The prefrontal cortex (PFC) is implicated in cognitive processes including working memory, temporal processing, decision making, flexibility, and goal-oriented behavior [1,2,3,4]
We found that Aβ inhibits PFC spontaneous network activity as well as the PFC activation induced by hippocampal fiber-activation both at the population and at the singlecell level, suggesting that Aβ might contribute to PFC dysfunction by a direct effect on this network as well as by a reduction in its synaptic innervation
This finding might constitute the cellular basis of several cognitive deficits that can be produced by PFC dysfunction and/or disrupted PFChippocampal coupling and are observed in both Alzheimer’s Disease (AD) patients and AD transgenic models
Summary
The prefrontal cortex (PFC) is implicated in cognitive processes including working memory, temporal processing, decision making, flexibility, and goal-oriented behavior [1,2,3,4]. Similar alterations in PFC function are observed in AD transgenic mice [9,10,11], which correlate with increased Aβ levels in the PFC and other connected brain areas [9, 11]. Alterations in PFC synaptic transmission [12] and plasticity [11], as well as in cell excitability [13] and in network activity [14], have been reported in AD transgenic mice. Some data indicate that these deleterious effects might be produced directly by the presence of Aβ in the PFC [15,16,17]
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