Modelling Homeostatic Plasticity in the CA3-CA1 Synapse in the Hippocampus

Abstract

Homeostatic synaptic scaling is a critical mechanism that allows neurons to maintain stable levels of synaptic activity. This process involves a variety of homeostatic changes, including the up or downregulation of AMPA receptor density in the postsynaptic PSD, changes in the density of glutamate transporters in astrocytic glia, and alterations in the kinetics of AMPA channels and release probability of glutamate. These changes are believed to be involved in the regulation of synaptic strength and plasticity, and their dysregulation has been implicated in several neurological disorders. To better understand the impact of homeostatic changes on synaptic function and plasticity, we developed a computational model to simulate the rapid synaptic current generated by AMPA receptors.Using this model, we observed that increasing AMPA receptor density, release probability of glutamate, and the open probability of AMPA receptors led to an increase in miniature excitatory postsynaptic current (mEPSC) amplitude. A significant finding from our study was that all homeostatic upscaling changes gave rise to paired pulse depression, which can regulate the balance between excitation and inhibition in neuronal networks. Finally, we incorporated all of these homeostatic changes into our model and observed an increase in mEPSC amplitude that was validated by experimental studies. These findings highlight the importance of homeostatic synaptic scaling in regulating synaptic function and plasticity, and may have important implications for the development of new treatments for neurological disorders that involve dysregulation of this critical process.