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

Abstract

The action potential and its all-or-none nature is fundamental to neural communication. These binary spikes are used by neurons to signal that a decision has been made; that their membrane potential has crossed a threshold either due to synaptic inputs or intrinsic mechanisms. Canonically the action potential is initiated once voltage-gated Na+ (Nav) channels are activated, these channels underpin the rapid upstroke of the action potential and their rapid kinetics give rise to the all-or-none nature of the action potential. Here we show that cerebrospinal fluid contacting neurons (CSFcNs) surrounding the central canal of the mouse spinal cord employ a different strategy. Rather than using Nav channels to generate binary spikes, CSFcNs use two different types of voltage-gated Ca2+ channel, enabling spikes of different amplitude. T-type Ca2+ channels are required for spontaneous spiking and generate lower amplitude spikes which signal purinergic inputs. In contrast large amplitude spikes require high voltage activated Cd2+ sensitive Ca2+ channels and these larger spikes signal cholinergic inputs. Our results show that the neurotransmitter impinging upon CSFcNs can be differentially signalled by the spike amplitude and this is supported by different types of voltage-gated Ca2+ channel. CSFcNs have recently been shown to be integral to coordinating posture and motor output in zebrafish and lamprey, our results show that these neurons can employ novel mechanisms to integrate and signal the neurotransmitter systems in which they are embedded.

GABA excitatory actions in cerebrospinal-fluid contacting neurones of adult mouse spinal cord

“…However, as a proportion of CSF-cNs still showed a GABA-induced [Ca 2+ ] i elevation in the presence of cadmium, we cannot exclude alternative mechanisms underlying the GABA-dependent [Ca 2+ ] i increase in CSF-cNs such as osmotic tension created by GABA A -Rs activation (Chavas et al ., 2004). Medullo-spinal CSF-cNs were shown to express both high-(N-type) and low-voltage (T-type) Ca 2+ channels (Marichal et al ., 2009; Jurčić et al ., 2019; Johnson et al ., 2022). Thus, even without generating action potentials, depolarising GABA may still induce [Ca 2+ ] i rise in CSF-cNs through the activation of T-Type Ca 2+ channels, as observed in other neuronal types (Fukuda et al ., 1998; Sun et al ., 2012).…”

“…Medullo-spinal CSF-cNs were shown to express both high-(N-type) and low-voltage (T-type) Ca 2+ channels (Marichal et al, 2009;Jurčić et al, 2019;Johnson et al, 2022). Thus, even without generating action potentials, depolarising GABA may still induce [Ca 2+ ]i rise in CSF-cNs through the activation of T-Type Ca 2+ channels, as observed in other neuronal types (Fukuda et al, 1998;Sun et al, 2012).…”