A systemic analysis of the ideas immanent in neuromodulation

This thesis focuses on the phenomena of neuromodulation — these are a set of diffuse chemical pathways that modify the properties of neurons and act in concert with the more traditional pathways mediated by synapses (neurotransmission). There is a growing opinion within neuroscience that such processes constitute a radical challenge to the centrality of neurotransmission in our understanding of the nervous system. This thesis is an attempt to understand how the idea of neuromodulation should impact on the canonical ideas of information processing in the nervous system. The first goal of this thesis has been to systematise the ideas immanent in neuromodulation such that they are amenable to investigation through both simulation and analytical techniques. Specifically, the physiological properties of neuromodulation are distinct from those traditionally associated with neurotransmission. Hence, a first contribution has been to develop a principled but minimal mechanistic description of neuromodulation. Furthermore, neuromodulators are thought to underpin a distinct set of functional roles. Hence, a second contribution has been to define these in terms of a set of dynami- cal motifs. Subsequently the major goal of thesis has been to investigate the relationship between the mechanistic properties of neuromodulation and their dynamical motifs in order to understand whether the physiological properties of neuromodulation predispose them toward their functional roles? This thesis uses both simulation and analytical techniques to explore this question. The most significant progress, however, is made through the application of dynamical systems analysis. These results demonstrate that there is a strong relationship between the mechanistic and dynamical abstractions of neuromodulation developed in this thesis. In particular they suggest that in contrast to neurotransmission, neuromodulatory pathways are predisposed toward bifurcating a system’s dynamics. Consequently, this thesis argues that a true canonical picture of the dynamics of the nervous system requires an appreciation of the interplay between the properties of neurotransmission and the properties immanent in the idea of neuromodulation.