State-Dependent Modification of Sensory Sensitivity via Modulation of Backpropagating Action Potentials

Abstract

Neuromodulators play a critical role in sensorimotor processing via various actions, including pre- and postsynaptic signal modulation and direct modulation of signal encoding in peripheral dendrites. Here we present a new mechanism that allows state-dependent modulation of signal encoding in sensory dendrites by neuromodulatory projection neurons. We studied the impact of antidromic action potentials (APs) on stimulus encoding using the anterior gastric receptor (AGR) neuron in the heavily modulated crustacean stomatogastric ganglion. We found that ectopic AP initiation in AGR's axon trunk is under direct neuromodulatory control by the inferior ventricular (IV) neurons, a pair of descending projection neurons. IV neuron activation elicited a long-lasting decrease in AGR ectopic activity. This modulation was specific to the site of AP initiation and could be mimicked by focal application of the IV neuron co-transmitter histamine. IV neuron actions were diminished after blocking H₂ receptors in AGR's axon trunk, suggesting a direct axonal modulation. This local modulation did not affect the propagation dynamics of en-passant APs. However, decreases in ectopic AP frequency prolonged sensory bursts elicited distantly near AGR's dendrites. This frequency-dependent effect was mediated via the reduction of antidromic APs, and the diminishment of backpropagation into the sensory dendrites. Computational models suggest that invading antidromic APs interact with local ionic conductances the rate constants of which determine the sign and strength of the frequency-dependent change in sensory sensitivity. Antidromic APs therefore provide descending projection neurons with a means to influence sensory encoding without affecting AP propagation or stimulus transduction.

Significance Statement Descending modulatory projection neurons are a hallmark of motor systems and fundamentally involved in sensorimotor processing. While they have been shown to interact on many levels with motor networks to dynamically and rapidly adjust motor and behavioral output, their actions on sensory neurons are not well understood. We found that descending projection neurons directly modulate action potential initiation in a sensory axon, diminishing the frequency of spontaneously generated ectopic action potentials that propagate antidromically into peripheral sensory dendrites. Changes in the frequency of these backpropagating action potentials determined the response of the sensory neuron to sensory stimuli. This suggests that descending projection neurons modulate sensory encoding by altering axonal membrane excitability and the frequency of antidromic action potential initiation.