The mammalian regulatory architecture: biobehavioral portals and the organization of physiological state

Abstract

Introduction Neuromodulatory interventions can produce overlapping adaptive outcomes despite engaging substantially different biological pathways. Pathway-centered approaches identify how interventions initially engage the nervous system and characterize pathway-specific mechanisms. Convergence across interventions raises an additional question: how can different biological routes influence overlapping domains of adaptive function? Methods This conceptual paper develops the Mammalian Regulatory Architecture (MRA), an organizational framework informed by identified mammalian synapomorphies (shared derived characteristics) and comparative anatomical, developmental, physiological, and functional observations. Results The MRA hypothesizes that mammalian evolution reorganized relationships among conserved regulatory processes through their integration with mammalian specializations and regulatory demands associated with nursing, prolonged developmental dependency, caregiving, co-regulation, and reciprocal social communication. The framework provides the basis for a biological portal model of neuromodulation that distinguishes the pathway of initial engagement from the functional significance of that engagement within the broader regulatory architecture. Whereas the pathway identifies how an intervention initially engages the nervous system, its portal significance concerns how that engagement influences state-regulating processes within the MRA. Discussion The proposed framework reframes neuromodulation from a process defined primarily by its neural target or pathway to one in which pathway engagement may influence broader regulatory organization, physiological state, Accessibility—the state-dependent availability of existing adaptive capacities—and adaptive function. It offers an organizational account of how distinct biological routes may influence overlapping domains of adaptive function.

The authors' abstract, as published at the source. Frontiers in Neuroscience, 2026 · DOI ↗