Deficits in taste-guided behaviors and central processing of taste in the transgenic TDP-43Q331K mouse model of frontotemporal dementia

Abstract

Frontotemporal dementia (FTD) is the second most prevalent form of presenile dementia. Patients with FTD show prominent chemosensory symptoms such as abnormal detection and recognition thresholds for various gustatory stimuli. The chemosensory symptoms of FTD may be related to damage of the gustatory insular cortex (GC) as the insular cortex is one of the primary targets in FTD disease progression. Little is known about how circuitry changes in GC lead to deficits in taste processing in FTD. Here we tested the hypothesis that gustatory deficits are present in a mouse model of FTD, and that they are related to abnormal patterns of neural activity in GC. We behaviorally evaluated a transgenic FTD mouse model overexpressing human TDP-43 with a Q331K mutation (TDP-43^Q331K) in a brief access test and a taste-based two alternative forced choice (2AFC) task probing the ability to discriminate sucrose/NaCl mixtures. TDP-43^Q331K mice showed abnormal sucrose consumption and an impaired ability to discriminate taste mixtures compared to non-transgenic control mice. To assess deficits in GC taste processing, we relied on electrophysiological recordings using chronically implanted tetrodes in alert TDP-43^Q331K and non-transgenic control mice. The proportion of taste-selective neurons in TDP-43^Q331K mice decreased over time compared to control mice. Similarly, encoding of chemosensory information and processing of taste palatability were impaired in TDP-43^Q331K mice compared to control mice. Overall, these results demonstrate taste-related symptoms in a mouse model of FTD and provide evidence for altered taste processing in GC of TDP-43^Q331K mice compared to control mice.