Acquisition of neuronal circuit architectures, central to understanding brain function and dysfunction, remains prohibitively challenging. Here I report the development of a simultaneous and sequential octuple-sexdecuple whole-cell patch-clamp recording system that enables architectural reconstruction of complex cortical circuits. The method unveils the canonical layer 1 single bouquet cell (SBC)-led disinhibitory neuronal circuits across the mouse somatosensory, motor, prefrontal, and medial entorhinal cortices. The ∼1,500-neuron modular circuits feature the translaminar, unidirectional, minicolumnar, and independent disinhibition and optimize cortical complexity, subtlety, plasticity, variation, and redundancy. Moreover, architectural reconstruction uncovers age-dependent deficits at SBC-disinhibited synapses in the senescence-accelerated mouse prone 8, an animal model of Alzheimer’s disease. The deficits exhibit the characteristic Alzheimer’s-like cortical spread and correlation with cognitive impairments. These findings decrypt operations of the elementary processing units in healthy and Alzheimer’s mouse cortices and validate the efficacy of octuple-sexdecuple patch-clamp recordings for architectural reconstruction of complex neuronal circuits. Display omitted •Octuple-sexdecuple patch recordings enable architectonics of complex cortical circuits•Architectonics identifies modular L1 SBC-led disinhibitory circuits across cortices•Architectures of L1 SBC-led disinhibitory circuits construe principles of cortical operation•Architectonics reveals specific deficits at SBC-disinhibited synapses in an AD mouse model Zhu introduced an octuple-sexdecuple patch-clamp recording technique, allowing for the architectural reconstruction of cortical L1 SBC-led modular circuits featuring translaminar, unidirectional, minicolumnar, and independent disinhibition. The architectures construe cortical operational principles and circuit- and connection-specific deficits at SBC-disinhibited synapses in the SAMP8 mouse, an Alzheimer’s disease model.