Information processing in the CNS: a supramolecular chemistry?

Abstract

How does central nervous system process information? Current theories are based on two tenets: (a) information is transmitted by action potentials, the language by which neurons communicate with each other-and (b) homogeneous neuronal assemblies of cortical circuits operate on these neuronal messages where the operations are characterized by the intrinsic connectivity among neuronal populations. In this view, the size and time course of any spike is stereotypic and the information is restricted to the temporal sequence of the spikes; namely, the "neural code". However, an increasing amount of novel data point towards an alternative hypothesis: (a) the role of neural code in information processing is overemphasized. Instead of simply passing messages, action potentials play a role in dynamic coordination at multiple spatial and temporal scales, establishing network interactions across several levels of a hierarchical modular architecture, modulating and regulating the propagation of neuronal messages. (b) Information is processed at all levels of neuronal infrastructure from macromolecules to population dynamics. For example, intra-neuronal (changes in protein conformation, concentration and synthesis) and extra-neuronal factors (extracellular proteolysis, substrate patterning, myelin plasticity, microbes, metabolic status) can have a profound effect on neuronal computations. This means molecular message passing may have cognitive connotations. This essay introduces the concept of "supramolecular chemistry", involving the storage of information at the molecular level and its retrieval, transfer and processing at the supramolecular level, through transitory non-covalent molecular processes that are self-organized, self-assembled and dynamic. Finally, we note that the cortex comprises extremely heterogeneous cells, with distinct regional variations, macromolecular assembly, receptor repertoire and intrinsic microcircuitry. This suggests that every neuron (or group of neurons) embodies different molecular information that hands an operational effect on neuronal computation.

Just One Brain Activity

“…Further, more reductionist approaches focus on the molecular levels of brain activity: see, for example, Jacobs et al (2007), Stankiewicz et al (2013), Ekstrand et al (2014), Gárate et al (2014). The last, but not the least, other techniques favor an approach that involves more than a single functional and anatomical level, tackling the issue of brain functions in terms of non-boundary wall domains spanning over every observational dimension and scale (Friston, 2010;Sporns, 2013;Tozzi, 2015). Consciousness, for example, does not seem to be confined to a single level (Koch et al, 2016).…”

Towards Dewetting Monoclonal Antibodies for Therapeutical Purposes

“…The recently-developed concept of "supramolecular chemistry" suggests that complex chemical entities, including the ones correlated with dewetting transition, can be reversibly built, starting from molecular components bound together by labile non-covalent interactions (Lehn 2007;Tozzi 2015). Through self-organized, self-assembled and dynamic transitory processes, the storage of information occurs at the molecular level, while its retrieval, transfer and processing at the supramolecular one.…”

Building a minimum frustration framework for brain functions over long time scales

“…Recent data indicate that the cortex is “phrenological.” That is, the cortex consists of extremely heterogeneous cells with distinct regional variations, macromolecular assembly, and intrinsic microcircuitry (Elston and Rockland, ; Spruston, ; Yates, ). This suggests that every neuron (or group of neurons) embodies different molecular information and displays different types of spiking responses (Haustein et al, ; Tozzi, ), even if they retain the same broad spectrum of energy mechanisms. This also suggests that every different brain function depends on changes in the phase space that take place in different anatomical areas or subareas.…”

“…For example, intraneuronal (changes in protein conformation, concentration, and synthesis [Kavalai et al, ]) and extraneuronal (such as extracellular proteolysis, substrate patterning, myelin plasticity, microbes, and metabolic status [Foster and McVey Neufeld, ; Marcoli et al, ]) factors may have cognitive connotations by themselves. Tozzi () recently introduced the concept of “supramolecular chemistry,” which involves the storage of information at the molecular level and its retrieval, transfer, and processing at the supramolecular level through transitory and labile, noncovalent processes that are self‐organized, self‐assembled, and dynamic (Lehn, ; Taylor and Ehenreich, ). Such a theory is a good starting point for evaluating an MFP for the nervous system; indeed, this operational approach, endowed in a macromolecular framework, is, formally, very close to the protein folding problem in which native interactions and residual contacts among molecular structures are of foremost prominence.…”

“…Many people, although emphasizing the molecular basis of synaptic plasticity, accept the idea that broad methodological investigation and general theories are required to advance our understanding of the brain further, despite the intrinsic simplifications offered by such general frameworks. Several global theories have been developed recently with respect to the nervous system's functions, such as the role of rhythms/oscillations (Buszaki and Watson, ), computational models (Magosso et al, ; Izhikevich, ), connectome (Van den Heuvel and Sporns, ), dynamical system theories, nonlinearity, metastability (Deco and Jirsa, ; Fraiman and Chialvo, ), Bayesian approaches and the free energy principle (FEP; Friston, ), information theory and multidimensional manifolds (Tononi, ; Sengupta et al, ), reductionist approaches based on atomic or molecular changes (Freeman and Vitiello, ), and supramolecular chemistry (Tozzi, ).…”