Long-term Regulation and Stability
The STNS played an important role in establishing the concept of homeostatic plasticity. There are many timescales at which neuronal and network mechanisms can be adjusted to adapt neural function to changing behavioral requirements. Considering all the activity- and neuromodulator dependent changes that circuits are subjected to in this context, there have to be mechanisms that ensure stable and robust function despite the constant flux and turnover of membrane proteins and their properties. In extreme cases, injury or other pathological conditions can be overcome by regulatory mechanisms that re-tune neuron and circuit properties to restore functional output.
Findings from the STNS and other system suggest that there are complex rules underlying the homeostatic regulation of intrinsic and synaptic properties. These include a mix of both activity-dependent and activity-independent mechanisms that ultimately govern the expression levels of membrane currents. One important observation is that very similar functional phenotypes of identified neurons can be produced by hugely variable levels of individual ionic currents, as long as the expression of different types of ion channels is properly balanced. Indeed, there are cell type-specific correlations in the expression levels of different currents.
More recently, in collaboration with the Schulz Lab at Missouri University, we have identified important roles for neuromodulators in homeostatic plasticity. First, the co-regulation of intrinsic voltage-gated ion channels appears to be critically dependent on the presence of neuromodulators, as deprivation from descending neuromodulatory input destroys these relationships. Second, neuromodulator receptors, and therefore neuronal responsiveness to neuromodulators, appear to be under the control of feedback mechanisms themselves. Our data show presumably compensatory up- or down-regulation of receptors in response to manipulations of activity and modulatory environment.
There is a vast literature on activity-dependent regulation of ionotropic synaptic receptors (e.g., AMPA receptors at mammalian synapses), but very little information on plasticity of metabotropic receptor expression. We are optimistic that the STG can serve as a trailblazer for our understanding of long-term regulation of neuromodulation.
Farzan Nadim
Office: 973-596-8453
Lab: 973-596-8290
Jorge Golowasch
Office: 973-596-8444
Lab: 973-596-8290
Dirk Bucher
Office: 973-596-8469
Lab: 973-596-6274