The Role Of The Cortical Neurons Of The Intrinsic Properties Of The Steady State Regulation Of The Neural Signals Encoding

The brain programs neural codes, including the patterns of synaptic transmission, the digital patterns of neuronal spikes and their non-synchronous outputs in neural network, precisely and loyally to guide well-organized behaviors, such as the motion, perception and cognition. In terms of neural codes at each of neurons, the patterns of sequential spikes (tonic and adaptive) as well as the timing precision and capacity of spikes are believed to be the critical parameters. Less is clear about how sodium channel-mediated intrinsic mechanisms set the spike programming, though synaptic inputs and potassium channels affect neuronal excitability. It is needed to elucidate such intrinsic mechanisms underlying the programming of sequential spikesWith electrophysiological and pharmacological approaches, we investigated the role of refractory periods for generating subsequent spikes and threshold potentials for evoking spikes in programming sequential spikes at cortical regular-spiking and fast-spiking neurons as well as cerebellar Purkinje cells. We also studied the kinetics of voltage-gated sodium channels, which is relevant to these intrinsic properties.Our results show that the patterns of sequential spikes at these three kinds of neurons in response to the given inputs from excitatory and inhibitory synapses are different, and that their spike patterns undergo plastic change with input intensities. To address the intrinsic mechanisms underlying such spike programming, we develop the methods to measure the refractory periods and threshold potentials of sequential spikes. We found that the values of spike capacity and timing precision at these neurons are associated with neuronal intrinsic properties, i.e., the shorter refractory periods and lower threshold potentials are associated with the higher spike capacity and the more precise spike timing, or vice versa. The capacity and timing precision of sequential spikes are linearly correlated with their refractory periods and threshold potentials. The enhanced excitatory inputs cause an increase in the spike capacity and timing precision through shortening refractory periods; and the inhibitory inputs immediately after each of spikes improve spike capacity and timing precision through lowering threshold potentials and refractory periods. Intracellular Ca²⁺ regulates the neuronal intrinsic properties, and in turn changes spike programming. With recording the activities of single voltage-gated sodium channels (VGSC), we found that VGSC- mediated intrinsic properties mechanistically navigate spike programming.Our data indicate that the programming of sequential spikes at central neurons is essentially controlled by VGSC-mediated intrinsic mechanisms, which are the central mechanisms for the change of spike patterns driven by synaptic inputs. Our studies provides fundamental approaches and clues for decoding the precise and loyal neural signals that guide the well-organized behaviors.