Graded spikes differentially signal neurotransmitter input in cerebrospinal fluid contacting neurons of the mouse...

The action potential and its all-or-none nature is fundamental to neural communication. Canonically, the action potential is initiated once voltage-activated Na⁺ channels are activated, and their rapid kinetics of activation and inactivation give rise to the action potential's all-or-none nature. Here we demonstrate that cerebrospinal fluid contacting neurons (CSFcNs) surrounding the central canal of the mouse spinal cord employ a different strategy. Rather than using voltage-activated Na⁺ channels to generate binary spikes, CSFcNs use two different types of voltage-activated Ca²⁺ channel, enabling spikes of different amplitude. T-type Ca²⁺ channels generate small amplitude spikes, whereas larger amplitude spikes require high voltage-activated Cd²⁺-sensitive Ca²⁺ channels. We demonstrate that these different amplitude spikes can signal input from different transmitter systems; purinergic inputs evoke smaller T-type dependent spikes whereas cholinergic inputs evoke larger spikes that do not rely on T-type channels. Different synaptic inputs to CSFcNs can therefore be signaled by the spike amplitude.