Cognitive decline is one of frequent challenges accompanying Alzheimer's disease (AD). However, little is known about the link between AD pathology and neural circuit mechanisms especially in frontal cortex essential for cognitive control behavior. Amyloid-β (Aβ) accumulation has been implicated as an upstream event in AD pathogenesis. Aβ-induced changes in synaptic function in experimental models of AD pathology suggest that Aβ may affect neural circuit connectivity essential for cognitive control behavior. Identification of cognitive circuit network vulnerable to Aβ accumulation would allow mitigating cognitive deficits in in AD. The goal of this study is to examine to what extent a frontal cognitive control circuit and associated network is vulnerable to early AD pathology. A recent study in mice demonstrated that frontal-sensory projections from anterior cingulate area (ACA) to visual cortex (VIS) (ACAvis) plays a causal role in cognitive control by improving attention especially after errors. In this study, we will analyze APP knock-in (KI) mice, which expresses mutant human APP under the endogenous mouse promoter while avoiding overexpression-associated artifacts, and test a hypothesis that AD-related amyloid pathology disrupts top-down frontal-sensory projection (Aim1) and frontal cholinergic neuromodulation (Aim2), and that the interaction between these systems contributes to cognitive control deficit (Aim3). To test this hypothesis, we will apply circuit specific approaches to monitor and manipulate neural activity in ACAvis projection neurons and basal forebrain cholinergic neurons during free moving cognitive control task using five choice serial reaction time task in APP KI mice.