Dr. Andreas Husch
Postdoctoral Fellow
German Center for Neurodegenerative Diseases (DZNE)
http://www.researchgate.net/profile/Andreas_Husch2
Postdoctoral Fellow
German Center for Neurodegenerative Diseases (DZNE)
http://www.researchgate.net/profile/Andreas_Husch2
Research Interest
Spinal cord injury causes two major problems for the restoration of locomotor function. First, it eliminates rapid synaptic and slow modulatory inputs from the brain to the spinal locomotor central pattern generator (CPG) network that are essential for normal activation of locomotion. Second, the isolated spinal cord undergoes slow denervation-induced changes, including alterations in synaptic strength and intrinsic properties of spinal neurons. This could affect the proper function of the CPG. Most current research on recovery from SCI focuses on the first problem. I hypothesize that the second problem is just as serious: if the CPG networks become dysfunctional over time due to the loss of descending synaptic and modulatory inputs, restoration of inputs may come too late to restore function. Therefore I am studying the effect of SCI on properties of locomotor controlling interneurons.
Spinal cord injury causes two major problems for the restoration of locomotor function. First, it eliminates rapid synaptic and slow modulatory inputs from the brain to the spinal locomotor central pattern generator (CPG) network that are essential for normal activation of locomotion. Second, the isolated spinal cord undergoes slow denervation-induced changes, including alterations in synaptic strength and intrinsic properties of spinal neurons. This could affect the proper function of the CPG. Most current research on recovery from SCI focuses on the first problem. I hypothesize that the second problem is just as serious: if the CPG networks become dysfunctional over time due to the loss of descending synaptic and modulatory inputs, restoration of inputs may come too late to restore function. Therefore I am studying the effect of SCI on properties of locomotor controlling interneurons.
It has been impossible to record stable from adult spinal interneurons, due to physical barriers such as myelination and a dense extracellular matrix. To enable the proposed SCI studies, initially, I have solved the 'age barrier' by a combination of new surgical techniques and the introduction of perforated patch recordings (Husch et al., 2011, J Neurophys). For the first time, I was able to study the intrinsic properties and serotonergic neuromodulation of identified interneurons in adult, behaviorally mature mouse spinal cords. With this essential baseline I examined the changes in intrinsic properties of identified interneurons after SCI (Husch et al., 2012, J Neurosci). For this purpose, I used transgenic mice that express cyan flurescent proteins in spinal V2a interneurons, which are ipsilaterally projecting glutamatergic interneurons contributing to left right coordination. Four weeks after a complete thoracic spinal cord lesion, V2a interneurons showed almost no changes in baseline excitability or action potential properties; the only parameter that changed was a reduced input resistance. However, V2a interneurons became 100-1000 fold more sensitive to 5-HT. Immunocytochemical analysis showed that SCI caused a coordinated loss of serotonergic fibers and the 5-HT transporter (SERT). It is likely that changes in the properties of locomotion coordinating interneurons impair recovery of locomotor function after SCI.
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Combination of the mouse spinal cord injury model and perforated patch recordings (PPR) in adult mice enabled the analysis of changes after SCI in the locomotor CPG (Husch et al. 2012)
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