Biology subjects

Drouillas, B.

Publications and source records attributed to Drouillas, B..

3 recordsLinked to original sources

bioRxiv2026

SK2/3 CHANNELS COUPLE WITH T-TYPE CA2+ CHANNELS TO GATE SPINAL LOCOMOTOR RHYTHM GENERATION

Initiating locomotion requires central pattern generator (CPG) interneurons to transition from tonic firing to persistent sodium current (INaP)-dependent bursting. While INaP provides the rhythmogenic drive, the conductances gating this transition remain unclear. Here, we show that functional coupling between small-conductance calcium-activated potassium (SK2/3) channels and low-threshold T-type Ca2+ channels, notably Cav3.2, gates locomotor rhythm generation. Pharmacological or genetic disruption of this SK-T-type axis triggers intrinsic bursting in Hb9 interneurons, a genetically identified rhythmogenic population of the locomotor CPG, and initiates fictive locomotion, whereas SK activation silences ongoing rhythmic output. Immunohistochemical co-expression of SK2, SK3 and Cav3.2 in Hb9 interneurons provides an anatomical basis for this functional coupling. Simulation-based inference further shows that, beyond this gating mechanism, burst diversity is primarily determined by the balance between INaP and M-type potassium conductances. Together, these findings identify SK-T-type coupling as a tunable brake on CPG activation, defining a biophysical module that controls the initiation and termination of locomotor rhythmic activity, with potential relevance for rhythmogenic circuits beyond locomotion.

neuroscience↗

bioRxiv2023

A size principle for bistability in mouse spinal motoneurons

Bistability in spinal motoneurons supports tonic spike activity in the absence of excitatory drive. Earlier work in adult preparations suggested that smaller motoneurons innervating slow antigravity muscle fibers are more likely to generate bistability for postural maintenance. However, whether large motoneurons innervating fast-fatigable muscle fibers display bistability related to postural tone is still controversial. To address this, we examined the relationship between soma size and bistability in lumbar ventrolateral -motoneurons of ChAT-GFP and Hb9-GFP mice across different developmental stages: neonatal (P2-P7), young (P7-P14) and mature (P21-P25). We found that as neuron size increases, the prevalence of bistability rises. Smaller -motoneurons lack bistability, while larger fast -motoneurons (MMP-9+/Hb9+) with a soma area [≥] 400{micro}m2 exhibit significantly higher bistability. Ionic currents associated with bistability, including the persistent Nav1.6 current, thermosensitive Trpm5 Ca2+-activated Na+ current and the slowly inactivating Kv1.2 current, also scale with cell size. Serotonin evokes full bistability in large motoneurons with partial bistable properties, but not in small motoneurons. Our study provides important insights into the neural mechanisms underlying bistability and how motoneuron size dictates this process. New and NoteworthyBistability is not a common feature of all mouse spinal motoneurons. It is absent in small, slow motoneurons but present in most large, fast motoneurons. This difference results from differential expression of ionic currents that enable bistability, which are highly expressed in large motoneurons but small or absent in small motoneurons. These results support a possible role for fast motoneurons in maintenance of tonic posture in addition to their known roles in fast movements.

neuroscience↗

bioRxiv2023

Persistent Nav1.6 current drives spinal locomotor functions through nonlinear dynamics

Persistent sodium current (INaP) in the spinal locomotor network promotes two distinct nonlinear firing patterns: a self-sustained spiking triggered by a brief excitation in bistable motoneurons and bursting oscillations in interneurons of the central pattern generator (CPG). Here, we identified the NaV channels responsible for INaP and their role in motor behaviors. We report the axonal Nav1.6 as the main molecular player for INaP in lumbar motoneurons. The motoneuronal inhibition of Nav1.6, but not of Nav1.1, impairs INaP, bistability, postural tone and locomotor performance. In interneurons of the CPG region, Nav1.6 with Nav1.1 equally mediate INaP and the inhibition of both channels is required to abolish oscillatory bursting activities and the locomotor rhythm. Overall, Nav1.6 plays a significant role both in posture and locomotion by governing INaP-dependent bistability in motoneurons and working in tandem with Nav1.1 to provide INaP-dependent rhythmogenic properties of the CPG.

neuroscience↗