The nervous system senses stimuli from the environment and commands muscles to respond. Sherrington, working with frog and cat spinal reflexes, proposed that neurons are not physically fused but communicate across a junction he named the synapse, where chemical or electrical signals pass. He also introduced the concept of the "reflex arc," in which multiple synaptic inputs are integrated in the spinal cord, demonstrating that the nervous system is an information-processing device, not mere wiring. Adrian, using fine glass microelectrodes, was the first to record action potentials from single sensory nerves and showed that stronger stimuli increase the firing rate—a principle known as frequency coding. Together their discoveries formed the groundwork of modern neuroscience and paved the way for technologies such as prosthetic limb control and visual aids.

In "The Integrative Action of the Nervous System" (1906), Sherrington formulated the idea that the spatial and temporal summation of excitatory and inhibitory synaptic inputs determines motor-neuron firing. His reflex-arc model implied that the central nervous system is a dynamic circuit that filters sensory input hierarchically to produce appropriate motor output. Adrian coupled cathode-ray oscilloscopes with vacuum-tube amplifiers to record action potentials from individual axons, demonstrating that spike amplitude is independent of stimulus strength and that firing frequency encodes information. He also analyzed adaptation in sensory receptors (muscle spindles, optic nerve), explaining how temporal contrast allows efficient information coding. Their combined work underpins modern concepts such as synaptic plasticity, central pattern generators, and artificial neuron models in computational neuroscience.

Sherrington’s formulation of synaptic integration, based on spinal reflex experiments and histological Golgi preparations, provided the conceptual framework for excitation–inhibition balance and for temporal/spatial summation at the postsynaptic membrane. His distinction between proprioceptive and exteroceptive reflexes presaged the modularity seen in modern sensorimotor circuits. Adrian’s single-unit recordings, employing differential AC amplification and high-impedance glass micropipettes, quantified the stochastic variability of inter-spike intervals and established rate coding as a robust scheme across modalities. He meticulously correlated receptor potentials with spike trains, thereby bridging electrophysiology and psychophysics. Together, their data validated the neuron doctrine, catalyzed Hodgkin–Huxley’s later ionic models, and still inform contemporary analyses of spike-train statistics, synaptic noise, and population coding in cortical and subcortical networks.