Reconciling flexible neuromodulation, variability and regulatory control in neurons

Nervous systems face two seemingly contradictory requirements: the need to maintain tight regulation of physiological properties, and the need to alter physiological properties in response to, or anticipation of, external events. Neuromodulation can induce widespread and rapid changes in the intrinsic and synaptic properties of neurons, sometimes for sustained periods of time. This underlies switches in behavioral state, such as activation of motor patterns or changes in arousal during sleeping and waking. On the other hand, so-called homeostatic plasticity mechanisms are believed to maintain activity at a set point and compensate for changes. How can these mechanisms coexist? I will show how physiologically grounded models of homeostatic regulation and neuromodulation can be reconciled, enabling stable maintenance of neuronal physiology while allowing for significant and long-lived switches in ongoing activity. A fundamental prediction is that this flexibility comes are a price: so-called homeostatic mechanisms will not always behave homeostatically. Time permitting, I will discuss how spare degrees of freedom in the large parameter space of physiological neural properties can permit robustness to global perturbations, such as changes in temperature.