Bidirectional flow of action potentials in axons drives activity dynamics in neuronal cultures

Abstract

Objective: Recent technological advances are revealing the complex physiology of the axon and challenging long-standing assumptions. Namely, while most action potential (AP) initiation occurs at the axon initial segment in central nervous system neurons, initiation in distal parts of the axon has been reported to occur in both physiological and pathological conditions. The functional role of these ectopic APs, if exists, is still not clear, nor its impact on network activity dynamics. Approach: Using an electrophysiology platform specifically designed for assessing axonal conduction we show here for the first time regular and effective bidirectional axonal conduction in hippocampal and dorsal root ganglia cultures. We investigate and characterize this bidirectional propagation both in physiological conditions and after distal axotomy. Main results: A significant fraction of APs are not coming from the canonical synapse-dendrite-soma signal flow, but instead from signals originating at the distal axon. Importantly, antidromic APs may carry information and can have a functional impact on the neuron, as they consistently depolarize the soma. Thus, plasticity or gene transduction mechanisms triggered by soma depolarization can also be affected by these antidromic APs. Conduction velocity is asymmetrical, with antidromic conduction being slower than orthodromic. Significance: Altogether these findings have important implications for the study of neuronal function in vitro, reshaping our understanding on how information flows in neuronal cultures.

Large-area electrical imaging having single neuron resolution using 236,880 electrodes CMOS-MEA technology

“…Interestingly, a backward signal propagation initiated from the distal part of the axon was observed in DRG neurons. Such bidirectional signal conduction was also recently reported in the organotypic DRG explants 113 . A backward propagation action potential is wildly explored in the central nervous system, and is thought to provide necessary conditions for synaptic plasticity 114 .…”

Cerebellar Activation Bidirectionally Regulates Nucleus Accumbens Core and Medial Shell

“…However, to the best of our knowledge, there is no evidence for DCN collaterals that form synapses onto NAc-projecting neurons in both VTA and intralaminar thalamic nuclei. Even if such collaterals existed, their activation would result in unreliable responses with relatively long latencies, due to synaptic delays and the failure-prone asymmetric nature of action potential conduction velocity (Grill et al, 2008; Mateus et al, 2021).…”

Nanoscale Patterning of In Vitro Neuronal Circuits

“…Though it is possible for segments of the axon to make thin protrusions (i.e., filopodia) with diameters thinner than 150 nm, the main axonal sections have a larger minimum diameter governed by the membrane periodic skeleton (e.g., actin rings). The axon diameter of rat hippocampal neurons in vitro is on average 450 nm. , By creating what can be considered submicron channels, which we will call nanochannels throughout the paper, with cross sections well below the axon diameter but similar in size or larger than dendritic spine necks, we wish to impose where and between which groups of neurons synapses can form (Figure B ii, iii). To validate this technique, we designed a neuronal circuit composed of three nodes (i.e., groups) of cells: one presynaptic and two postsynaptic.…”