Abnormal Population Responses in the Somatosensory Cortex of Alzheimer’s Disease Model Mice

Abstract

Alzheimer’s disease (AD) is the most common form of dementia. One of the neuropathological hallmarks of AD is the accumulation of amyloid-β plaques. Overexpression of human amyloid precursor protein in transgenic mice induces hippocampal and neocortical amyloid-β accumulation and plaque deposition that increases with age. The impact of these effects on neuronal population responses and network activity in sensory cortex is not well understood. We used Voltage Sensitive Dye Imaging, to investigate at high spatial and temporal resolution, the sensory evoked population responses in the barrel cortex of aged transgenic (Tg) mice and of age-matched non-transgenic littermate controls (Ctrl) mice. We found that a whisker deflection evoked abnormal sensory responses in the barrel cortex of Tg mice. The response amplitude and the spatial spread of the cortical responses were significantly larger in Tg than in Ctrl mice. At the network level, spontaneous activity was less synchronized over cortical space than in Ctrl mice, however synchronization during evoked responses induced by whisker deflection did not differ between the two groups. Thus, the presence of elevated Aβ and plaques may alter population responses and disrupts neural synchronization in large-scale networks, leading to abnormalities in sensory processing.

Enhanced Cerebral Blood Volume under Normobaric Hyperoxia in the J20-hAPP Mouse Model of Alzheimer’s Disease

“…Therefore, the hyperexcitability seen in the J20-AD mouse, APP/PS1 mice and younger AD-patients may be related to the brains initial reaction to the emerging presence of Aβ oligomers, or that of aberrant APP processing. Whisker deflection in APP/PS1 mice also resulted in much higher neural responses in the cortex, also supporting our findings 28 . In our study, the observed enhanced neural activity couples well with the enhanced haemodynamic responses, suggesting that neurovascular coupling in the J20-AD mouse is intact and functioning well at this younger age of 6-9m.…”

Quasi-Periodic Patterns of Neural Activity improve Classification of Alzheimer’s Disease in Mice

“…A study in APPswe mice used whisker stimulation and voltage sensitive dye imaging to correlate Aβ plaques with abnormal neural population responses in the somatosensory cortex and with reduced cortical synchronization during spontaneous activity 96 . This matches our observation of a dysfunctional TPN.…”

Whisker exploration behaviours in the 5xFAD mouse are affected by sex and retinal degeneration

“…Therefore, if both motor deficits and anxiety‐like behaviour are unlikely in the 5xFAD mice, changes in whisker behaviour may be due to alterations in sensory processing. It has been suggested that 5xFAD mice might have hypersensitive whiskers due to a reduction of inhibition in the barrel cortex, with the barrel cortex producing large amplitude neural responses with a broad spatial spread following a whisker deflection . It may be that whisker signals are not processed efficiently in the cortex, therefore, their exploratory movements increase to gain more sensory information; or that they are over‐sensitive, so decrease whisker angular positions in order to reduce the force applied to the whisker from an object contact.…”

“…It has been suggested that 5xFAD mice might have hypersensitive whiskers due to a reduction of inhibition in the barrel cortex, 11 with the barrel cortex producing large amplitude neural responses with a broad spatial spread following a whisker deflection. 44 It may be that whisker signals are not processed efficiently in the cortex, therefore, their exploratory movements increase to gain more sensory information; or that they are over-sensitive, so decrease whisker angular positions in order to reduce the force applied to the whisker from an object contact. Further investigations into whisker object contacts and forces in 5xFAD mice might help to tease apart these hypotheses (ie, Campagner et al 45 ).…”