IA monosynaptic pathway in SODI mouse model of amyothropic lateral sclerosis

• Autorzy: Baczyk M. , Martinot C. , Delestree N. , Manuel M. , Zytnicki D.
• Języki publikacji: EN

Abstrakty

EN

BACKGROUND AND AIMS: Glutamate excitotoxicity has long been suggested to contribute to the degeneration of motoneurons in Amyotrophic Lateral Sclerosis (ALS). However, it has recently been shown that spinal motoneurons do not display an intrinsic hyperexcitability just prior to their degeneration in SOD1 G93A mice, the standard model of ALS. Furthermore average densities of excitatory (VGLUT1 and VGLUT2) and inhibitory (VGAT) boutons on the dendritic tree and the soma of affected motoneurons were unchanged. However glutamate excitotoxicity can still take place if excitatory pathways are more active. Therefore the aim of this study was to investigate the excitability of the monosynaptic Ia pathway in SOD1 mice. METHODS: Eight SOD1 G93A and six SOD WT control mice were used in this study. Intracellularly penetrated motoneurons were identified as a medial gastrocnemius (MG) or lateral gastrocnemius (LG) motoneurons by their threshold for antidromic activation. Ia monosynaptic EPSPs were recorded from these motoneurons after stimulation of their homonymous nerve. In parallel the afferent Ia volley was recorded from the cord dorsum. Increasing stimulation intensities were used to obtain minimum and maximum Ia Volleys and EPSPs. RESULTS: The average amplitudes of monosynaptic Ia EPSPs in SOD1 motoneurons were significantly smaller when compared to SOD WT controls (1.40 mV and 2.24 mV, respectively). Moreover the EPSP difference was mainly visible for the group of motoneurons characterized by high input resistance (above 3 MΩ). On the other hand, the recruitment curves (normalized amplitude vs. stim intensity) of Ia volleys and EPSPs were unchanged, suggesting no change in excitability of Ia fibers but alterations in Ia monosynaptic synapses. CONCLUSIONS: Results indicate alterations in Ia monosynaptic pathway in presymptomatic SOD1 ALS mouse model. This can stem from several reasons, e.g. increased presynaptic inhibition of Ia terminals or reduced efficacy of post-synaptic receptors.

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2015
• Tom: 75
• Numer: Supl.
• Opis fizyczny: p.S72

Twórcy

autor

Baczyk M.

• Laboratory of Neuropysics and Physiology, UMR CNRS 8119, University Paris Descartes, Paris, France

autor

Martinot C.

• Laboratory of Neuropysics and Physiology, UMR CNRS 8119, University Paris Descartes, Paris, France

autor

Delestree N.

• Laboratory of Neuropysics and Physiology, UMR CNRS 8119, University Paris Descartes, Paris, France

autor

Manuel M.

• Laboratory of Neuropysics and Physiology, UMR CNRS 8119, University Paris Descartes, Paris, France

autor

Zytnicki D.

• Laboratory of Neuropysics and Physiology, UMR CNRS 8119, University Paris Descartes, Paris, France