Long-Term Activity-Dependent Plasticity of Action Potential Propagation Delay and Amplitude in Cortical Networks

Abstract

BackgroundThe precise temporal control of neuronal action potentials is essential for regulating many brain functions. From the viewpoint of a neuron, the specific timings of afferent input from the action potentials of its synaptic partners determines whether or not and when that neuron will fire its own action potential. Tuning such input would provide a powerful mechanism to adjust neuron function and in turn, that of the brain. However, axonal plasticity of action potential timing is counter to conventional notions of stable propagation and to the dominant theories of activity-dependent plasticity focusing on synaptic efficacies.Methodology/Principal FindingsHere we show the occurrence of activity-dependent plasticity of action potential propagation delays (up to 4 ms or 40% after minutes and 13 ms or 74% after hours) and amplitudes (up to 87%). We used a multi-electrode array to induce, detect, and track changes in propagation in multiple neurons while they adapted to different patterned stimuli in controlled neocortical networks in vitro. The changes did not occur when the same stimulation was repeated while blocking ionotropic gabaergic and glutamatergic receptors. Even though induction of changes in action potential timing and amplitude depended on synaptic transmission, the expression of these changes persisted in the presence of the synaptic receptor blockers.Conclusions/SignificanceWe conclude that, along with changes in synaptic efficacy, propagation plasticity provides a cellular mechanism to tune neuronal network function in vitro and potentially learning and memory in the brain.

Superresolution imaging reveals activity-dependent plasticity of axon morphology linked to changes in action potential conduction velocity

“…Although activity-dependent changes in AP conduction velocity and synaptic delay have been reported before (16)(17)(18)(19), their underlying mechanisms have remained elusive. On the basis of STED imaging in living brain tissue, we present evidence for activity-driven changes in presynaptic boutons and axon shafts that were accompanied by bidirectional changes in AP conduction delay.…”

Axon Physiology

“…Differential conduction delays in axonal branches participate in precise temporal coding in the barn owl auditory system (95,96,358). But the role of axonal delays has only been studied in artificial neural networks (87, 271, 344) or in vitro neuronal circuits (33), and additional work will have to be done to describe its implication in hybrid (i.e., neuron-computer) or in in vivo networks. Furthermore, understanding the conflict faced by cortical axons between space (requirement to connect many different postsynaptic neurons) and time (conduction delay that must be minimized) will require further studies (83).…”

Tradeoffs and Constraints on Neural Representation in Networks of Cortical Neurons

“…The immediate response may last for up to 25 ms following a stimulus, however more then 95% of its spikes are confined to the first 10 ms (Bakkum et al, 2008;Shahaf et al, 2008; supplemental Item 1, available at www.jneurosci.org as supplemental material); therefore, the first 10 ms following each stimulus were excluded from the data. While data beyond this limit might contain, in a very low probability, a small fraction of spikes that were directly activated by the stimulus, we chose not to exclude spikes beyond 10 ms since the data there is made of mostly synaptically mediated response.…”