Effects on brain cell function Spike generation

Nonsynaptic plasticity has an excitatory effect on the generation of spikes. The increase in spike generation has been correlated with a decrease in the spike threshold,^[4] a response from nonsynaptic plasticity. This response can result from the modulation of certain presynaptic K⁺ currents; I_A,I_K,Ca,and I_Ks, which work to increase the excitability of the sensory neurons, broaden the action potential, and enhance neurotransmitter release. These modulations of K⁺ conductances serve as common mechanisms for regulating excitability and synaptic strength.^[5]

Regulation of synaptic plasticity

Nonsynaptic plasticity has been linked with synaptic plasticity, via both synergistic and regulatory mechanisms. The degree of synaptic modification determines the polarity of nonsynaptic changes, affecting the change in cellular excitability. Moderate levels of synaptic plasticity produce nonsynaptic changes that will synergistically act with the synaptic mechanisms to strengthen a response. Conversely, more robust levels of synaptic plasticity will produce nonsynaptic responses that will act as a negative-feedback mechanism. The negative feedback mechanisms work to protect against saturation or suppression of the circuit activity as a whole.^[5]

Higher brain function involved with nonsynaptic plasticity Long-term associative memory Experimental evidence

The experiment of Kemenes et al^[6] showed that in an extrinsic modulatory neuron, nonsynaptic plasticity influences the expression of long-term associative memory. The relationship between nonsynaptic plasticity and memory was assessed using cerebral giant cells (CGCs). Depolarization from conditioned stimuli increased the neuronal network response and occurred postcondtionally. This depolarization lasted as long as the long-term memory. Persistent depolarization and behavioral memory expression occurred more than 24 hours after posttraining, indication long-term effects. In this experiment, the electrophysiological expression of the long-term memory trace was a conditioned stimulus induced fictive feeding response. CGCs were significantly more depolarized in the trained organisms than the control group, indicating association with learning and excitability changes. When CGCs were depolarized, they showed an increased response to the conditional stimuli and a stronger fictive feeding response. This demonstrated that the depolarization is enough to produce a significant fictive feeding response to the conditioned stimuli. Therefore, the depolarization as a result of learning makes a large impact to long-term memory by the activation of the conditioned behavior by the conditioned stimuli. Additionally, no significant difference was observed in the fictive feeding rates between conditioned organisms and ones that were artificially depolarized, reaffirming that depolarization is sufficient to generate the behavior associated with long-term memory.^[6]

Nonsynaptic processes and memory storage

Nonsynaptic activity in the cell is usually expressed as changes in neuronal excitability. This occurs through modulation of membrane components, such as resting and voltage-gated channels and ion pumps. Nonsynaptic processes are thought to be involved in memory storage. One possible mechanism of this action involves marking a neuron that has been recently active with changes in excitability. This would help to link temporally separated stimuli. Another potential mechanism comes from a computational model that indicates that nonsynaptic plasticity may prime circuits for modification in learning because excitability changes may regulate the threshold for synaptic plasticity.^[5]