Biology subjects

Baczyk, M.

Publications and source records attributed to Baczyk, M..

3 recordsLinked to original sources

bioRxiv2024

Anodal tsDCS restores the structure and function of the disrupted proprioceptive Ia synapses on spinal motoneurons in the SOD1 G93A mouse model of ALS

An imbalance between cells intrinsic excitability and synaptic excitation levels is the basis of spinal motoneuron (MN) pathophysiology in Amyotrophic Lateral Sclerosis. Recently, a restoration of the deficient Ia synaptic excitation of spinal MNs was achieved by applying acute trans-spinal direct current stimulation (tsDCS) to presymptomatic SOD1 G93A mice. Here we investigate whether two-week repeated tsDCS applied to presymptomatic SOD1 animals can provoke spinal MN neuroplasticity and reduce the disease burden. Anodal, cathodal or sham polarisation of 100 {micro}A was applied to P30-P35 SOD1 G93A mice; passive membrane properties and Ia excitatory post-synaptic potential (EPSP) characteristics were investigated by intracellular recordings of spinal MNs in vivo. A second cohort of polarized animals was used to test the impact of our intervention on Ia synapse morphology, MN intracellular metabolic pathways activity, and disease markers. Anodal tsDCS evoked a strong increase in maximal Ia EPSPs, coupled with a significant upregulation of vesicular glutamate transporter levels and GlurR4 subunits of AMPA receptors at the Ia synapse. On the other hand, cathodal polarisation failed to induce any significant alteration to Ia synapse morphology but did increase both peak and plateau input resistance and recovered the abnormal paired-pulse ratio. Unexpectedly, the changes in MN electrophysiological profile and Ia synapse morphology did not translate into alterations of intracellular pathways ctivity and did not decrease the disease burden. Altogether our results indicate a strong polarity-dependent plasticity of spinal MNs in SOD1 G93A mice in response to tsDCS, which nevertheless appears insufficient to alter disease dynamics. HighlightsO_LI14-days of trans-spinal direct current stimulation (tsDCS) alters the electrophysiological properties and morphology of Ia proprioceptive synapses on spinal MNs in SOD1 G93A mouse model of ALS C_LIO_LIAnodal (depolarising) tsDCS increases MN synaptic excitation and restores the postsynaptic elements of the Ia synapse C_LIO_LICathodal (hyperpolarising) tsDCS increases MN input resistance but does not impact Ia synapse morphology C_LIO_LIBoth anodal and cathodal tsDCS fail to significantly modify the cellular burden of the disease C_LI

neuroscience↗

bioRxiv2024

Spinal microcircuits go through multiphasic homeostatic compensations in a mouse model of motoneuron degeneration

In many neurological conditions, early-stage neural circuit adaption can preserve relatively normal behaviour. In some diseases, spinal motoneurons progressively degenerate yet movement is initially preserved. We therefore investigated whether these neurons and associated microcircuits adapt in a mouse model of progressive motoneuron degeneration. Using a combination of in vitro and in vivo electrophysiology and super-resolution microscopy, we found that, early in the disease, neurotransmission in a key pre-motor circuit, the recurrent inhibition mediated by Renshaw cells, is reduced by half due to impaired quantal size associated with decreased glycine receptor density. This impairment is specific, and not a widespread feature of spinal inhibitory circuits. Furthermore, it recovers at later stages of disease. Additionally, an increased probability of release from proprioceptive afferents leads to increased monosynaptic excitation of motoneurons. We reveal that in motoneuron degenerative conditions, spinal microcircuits undergo specific multiphasic homeostatic compensations that may contribute to preservation of force output.

neuroscience↗

bioRxiv2024

Non-canonical adrenergic neuromodulation of motoneuron intrinsic excitability through beta-receptors in wild-type and ALS mice

Homeostatic feedback loops are essential to stabilize the activity of neurons and neuronal networks. It has been hypothesized that, in the context of Amyotrophic Lateral Sclerosis (ALS), an excessive gain in feedback loops might hyper- or hypo-excite motoneurons (MNs) and contribute to the pathogenesis. Here, we investigated how the neuromodulation of MN intrinsic properties is homeostatically controlled in presymptomatic adult SOD1(G93A) mice and in the age-matched control WT mice. First, we determined that {beta}2 and {beta}3-adrenergic receptors, which are Gs-coupled receptors and subject to tight and robust feedback loops, are specifically expressed in spinal MNs of both SOD1 and WT mice at P45. We then demonstrated that these receptors elicit a so-far overlooked neuromodulation of the firing and excitability properties of MNs. These electrical properties are homeostatically regulated following receptor engagement, which triggers ion channel transcriptional changes and downregulates those receptors. These homeostatic feedbacks are not dysregulated in presymptomatic SOD1 mice, and they set the MN excitability upon {beta}-adrenergic neuromodulation.

neuroscience↗