research

How spinal microcircuits generate, regulate and preserve motor function in health and neuromuscular disease.

Our research is centred on understanding how spinal cord microcircuits generate, regulate and preserve motor function in health and neurological disease, with a particular focus on neuromuscular disorders. We are especially interested in how homeostatic and adaptive mechanisms operate within spinal circuits, and how their failure or maladaptation contributes to disease onset and progression.

A defining feature of the lab is the integration of mechanistic studies in animal models with directly comparable, non-invasive approaches in humans, so that basic neurophysiology and clinical neuroscience stay closely aligned.

Diagram of spinal cord circuits: motoneurons, Renshaw cells, Ia inhibitory interneurons and CSP inhibitory interneurons, with Ia afferents from muscle spindles and A-delta fibres from cutaneous hindlimb afferents.
The spinal circuits we study: motoneurons and the inhibitory interneurons that shape their output (Renshaw cells, Ia inhibitory interneurons and cutaneous silent period (CSP) inhibitory interneurons), together with sensory inputs from muscle spindles and the skin.

Spinal microcircuits in neuromuscular disease

We investigate the cellular properties and synaptic function of the spinal circuits that control movement, including motoneurons and premotor interneuron populations. We examine how intrinsic properties, neuromodulatory systems and circuit connectivity shape motor output under normal conditions, and how these processes are altered in disease, particularly ALS.

In ALS, clinical weakness emerges only after more than 50% of the motoneurons have denervated a single muscle, reflecting the remarkable capacity of the central nervous system for compensation. A major goal of the lab is to identify the homeostatic adaptations in spinal microcircuits that preserve function before clinical decline, and to define windows of neuronal resilience that may be exploited for improved diagnosis, prognosis and therapeutic intervention.

Schematic of retrograde labelling of tibialis anterior and gastrocnemius motoneurons and preparation of a longitudinal spinal cord slice.
Retrograde labelling of tibialis anterior (TA) and gastrocnemius (GS) motoneurons, followed by preparation of the lumbar spinal cord.
Microscopy images of labelled TA and GS motor pools in the spinal cord.
Identifying labelled motor pools (green and red) in the spinal cord preparation.
Schematic of a longitudinal spinal cord preparation with L4 and L5 dorsal root stimulation and motoneuron recording.
Longitudinal spinal cord preparations: stimulating the L4/L5 dorsal roots activates Ia afferents while we record from identified motoneurons.
Schematic of motoneuron recording with ventral root stimulation to recruit Renshaw cells.
Ventral root stimulation recruits recurrent inhibition through Renshaw cells while motoneurons are recorded.
Whole-cell voltage-clamp traces of synaptic currents at holding potentials of -60 mV and 0 mV.
Whole-cell voltage-clamp recordings of synaptic currents at holding potentials of −60 mV and 0 mV.
Confocal images of a motoneuron with high-magnification views of synaptic contacts.
High-resolution imaging of synaptic contacts on motoneurons.

Translational neurophysiology: from mice to humans

We combine in vitro, ex vivo and in vivo electrophysiology in mouse models with high-density surface electromyography (HDsEMG) in humans to study spinal microcircuits across species. The strong similarity of the neuromuscular system between species, together with directly comparable electrophysiological approaches, lets us probe mechanisms and function in parallel in mice and humans. Our goal is to identify and validate non-invasive spinal circuit biomarkers for disease staging, prognosis and longitudinal monitoring in patients.

Schematic of HDsEMG recording from a hand muscle during stimulation of digital nerves, with raw EMG decomposed into motor unit spike trains.
In people, HDsEMG electrode grids record muscle activity non-invasively. A decomposition algorithm separates the raw signals into the spike trains of individual motor units, and stimulation of digital nerves lets us probe inhibitory spinal circuits.
Peristimulus time histograms and peristimulus frequencygrams with CUSUM traces for three motor units, showing inhibition duration.
Each decoded motor unit reveals how strongly and for how long it is inhibited after stimulation (PSTH-CUSUM and PSF-CUSUM analyses).
Schematic of sciatic nerve stimulation in mice with recordings from tibialis anterior and gastrocnemius, and example M-wave and H-reflex traces.
The same reflex measures in mice: sciatic nerve stimulation evokes M-waves and H-reflexes in tibialis anterior and gastrocnemius, allowing direct comparison with human recordings.

Methods we use

Cells & synapses

In vitro electrophysiology

Whole-cell patch-clamp of identified motoneurons and interneurons in spinal cord slices and longitudinal preparations.

Circuits

Ex vivo & in vivo recordings

Root and nerve stimulation, reflex testing and EMG in mouse models of neuromuscular disease.

People

HDsEMG & motor unit decoding

Non-invasive recordings of many motor units at once, used to map spinal circuit function in health and disease.

Anatomy

Tracing & imaging

Retrograde labelling, immunohistochemistry and high-resolution microscopy of synaptic contacts.