Selective Persistence of Sensorimotor Mismatch Signals in Visual Cortex of Behaving Alzheimer's Disease Mice

Neurodegenerative processes in Alzheimer's disease (AD) affect the structure and function of neurons [1-4], resulting in altered neuronal activity patterns comprising neuronal hypo- and hyperactivity [5, 6] and causing the disruption of long-range projections [7, 8]. Impaired information processing between functionally connected brain areas is evident in defective visuomotor integration, an early sign of the disease [9-11]. The cellular and neuronal circuit mechanisms underlying this disruption of information processing in AD, however, remain elusive. Recent studies in mice suggest that visuomotor integration already occurs in primary visual cortex (V1), as it not only processes sensory input but also exhibits strong motor-related activity, likely driven by neuromodulatory or excitatory inputs [12-17]. Here, we probed the integration of visual-and motor-related-inputs in V1 of behaving APP/PS1 [18] mice, a well-characterized mouse model of AD, using two-photon calcium imaging. We find that sensorimotor signals in APP/PS1 mice are differentially affected: while visually driven and motor-related signals are strongly reduced, neuronal responses signaling a mismatch between expected and actual visual flow are selectively spared. We furthermore observe an increase in aberrant activity during quiescent states in APP/PS1 mice. Jointly, the reduction in running-correlated activity and the enhanced aberrant activity degrade the coding accuracy of the network, indicating that the impairment of visuomotor integration in AD is already taking place at early stages of visual processing.