Srinivas Gorur Shandilya, PhD  

Postdoctoral Research Fellow
Marder Lab
Brandeis University
(September 26, 2019)

Compensation of size change coexists with sensitivity to perturbations in a model of neuronal homeostasis

Consider the size of the brain of a newborn baby. Now consider the same brain once it has grown to adult size. How do the physical changes of the brain affect function? Dr. Shandilya discussed his research modeling the neuronal circuits in lobsters and crabs and how they maintain homeostasis (steady, stable functioning) despite changes to size over time.

Cells in the nervous systems can increase in size dramatically during growth. In many animals neurons must preserve the manner in which they function across several length scales. For example, neurons in well-studied circuits in crabs and lobsters generate similar activity patterns despite large increases in their size and changes in structure.

The fact that neurons can preserve their behavior of many length scales hints at regulatory mechanisms that compensate for size changes by somehow altering membrane currents. Using conductance-based neuron models, we asked whether simple activity-dependent feedback can maintain intrinsic behavior in a neuron as its size is varied. In our models, despite relying only on a single sensor that measures time-averaged intracellular calcium as a proxy for activity, we found that this regulation mechanism could regulate conductance densities of ion channels, and was robust to changes in the size of the neuron.

By mapping changes in cell size onto perturbations in the space of conductance densities of all channels, we show how robustness to size change coexists with sensitivity to perturbations that alter the ratios of maximum conductances of different ion channel types. Our findings suggest that biological regulation that is optimized for coping with expected perturbations such as size changes will be vulnerable to other kinds of perturbations such as channel deletions.