Received concepts of neural activity, building on the technical concepts of information processing and coding, do not formulate the problems that an organism must formulate in order to cope with its environment. Specifically, this includes the problems of self-maintenance and adaptation, and how such activities are to be monitored and corrected in case of their (anticipated) deviation from viable norms. In this paper, it is shown how the functional systems theory of P. K. Anokhin formulated key notions of adaptive control, self-monitoring, and self-detectable (“system-detectable”) error that directly anticipate current debates on neural information and representation, and allow to reframe these debates in new empirical and theoretical perspectives. In addition to showing this on the basis of early (less known and untranslated) works, we analyze how functional systems pose new questions for current research. Specifically, recent discoveries in integrative and cellular neuroscience regarding the biophysical limits of signal summation in neural cells directly confirm Anokhin’s analysis of the integrative activities of the neuron. These findings may have wide implications, and call for new and biologically more specific models of the integrative and semiotic closure of nervous activity, in line with the systemic closure of the organismic functions in which they participate.