Anodal transcranial direct current stimulation alleviates cognitive impairment in an APP/PS1 model of Alzheimer’s disease in the preclinical stage

Anodal transcranial direct current stimulation(AtDCS)has been shown to alleviate cognitive impairment in an APP/PS1 model of Alzheimer’s disease in the preclinical stage.However,this enhancement was only observed immediately after AtDCS,and the long-term effect of AtDCS remains unknown.In this study,we treated 26-week-old mouse models of Alzheimer’s disease in the preclinical stage with 10 AtDCS sessions or sham stimulation.The Morris water maze,novel object recognition task,and novel object location test were implemented to evaluate spatial learning memory and recognition memory of mice.Western blotting was used to detect the relevant protein content.Morphological changes were observed using immunohistochemistry and immunofluorescence staining.Six weeks after treatment,the mice subjected to AtDCS sessions had a shorter escape latency,a shorter path length,more platform area crossings,and spent more time in the target quadrant than sham-stimulated mice.The mice subjected to AtDCS sessions also performed better in the novel object recognition and novel object location tests than sham-stimulated mice.Furthermore,AtDCS reduced the levels of amyloid-β42 and glial fibrillary acidic protein,a marker of astrocyte activation,and increased the level of neuronal marker NeuN in hippocampal tissue.These findings suggest that AtDCS can improve the spatial learning and memory abilities and pathological state of an APP/PS1 mouse model of Alzheimer’s disease in the preclinical stage,with improvements that last for at least 6 weeks.

Corticostriatal Neurons in the Anterior Auditory Field Regulate Frequency Discrimination Behavior

The anterior auditory field(AAF)is a core region of the auditory cortex and plays a vital role in discrimination tasks.However,the role of the AAF corticostriatal neurons in frequency discrimination remains unclear.Here,we used c-Fos staining,fiber photometry recording,and pharmacogenetic manipulation to investigate the function of the AAF corticostriatal neurons in a frequency discrimination task.c-Fos staining and fiber photometry recording revealed that the activity of AAF pyramidal neurons was significantly elevated during the frequency discrimination task.Pharmacogenetic inhibition of AAF pyramidal neurons significantly impaired frequency discrimination.In addition,histological results revealed that AAF pyramidal neurons send strong projections to the striatum.Moreover,pharmacogenetic suppression of the striatal projections from pyramidal neurons in the AAF significantly disrupted the frequency discrimination.Collectively,our findings show that AAF pyramidal neurons,particularly the AAF–striatum projections,play a crucial role in frequency discrimination behavior.