Regulating Temporal Neural Coding via Fast and Slow Synaptic Dynamics

The NMDA receptor (NMDAR), as a ubiquitous type of synapse in neural systems of the brain, presents slow dynamics to modulate neural spiking activity. For the cerebellum, NMDARs have been suggested for contributing complex spikes in Purkinje cells (PCs) as a mechanism for cognitive activity, learning, and memory. Recent experimental studies are debating the role of NMDAR in PC dendritic input, yet it remains unclear how the distribution of NMDARs in PC dendrites can affect their neural spiking coding properties. In this work, a detailed multiple-compartment PC model was used to study how slow-scale NMDARs together with fast-scale AMPA, regulate neural coding. We find that NMDARs act as a band-pass filter, increasing the excitability of PC firing under low-frequency input while reducing it under high frequency. This effect is positively related to the strength of NMDARs. For a response sequence containing a large number of regular and irregular spiking patterns, NMDARs reduce the overall regularity under high-frequency input while increasing the local regularity under low-frequency. Moreover, the inhibitory effect of NMDA receptors during high-frequency stimulation is associated with a reduced conductance of large conductance calcium-activated potassium (BK) channel. Taken together, our results suggest that NMDAR plays an important role in the regulation of neural coding strategies by utilizing its complex dendritic structure.