Neural Control of Movement - Copenhagen > Research > Morphology of plateau ...
Morphological bases of plateau potential in physiological and pathological conditions
We have 2 directions of research within this area:
- Research direction I. Calcium channel Cav1.3 expression in normal animals
- Research direction II. Unravelling the molecular and cellular mechanisms of spasticity: expression changes of 5-HT receptors and intraspinal 5-HT neurons after spinal lesion
Research direction I. Calcium channel Cav1.3 expression in normal animals
One of the intrinsic properties of the spinal motoneurons is the production of plateau potentials, which has been shown to exist in many vertebrates including turtles, mice, rats, cats and perhaps humans. The underlying mechanism of plateau potentials is a voltage-dependent persistent inward current. To a large extent plateau potentials are mediated by L-type calcium channels, in which the most important one is CaV1.3. The spatial localization of persistent inward currents along the somatodendritic membrane is an important issue for explaining the electrophysiological findings on the recruitment of plateau potentials. A large body of physiological evidence has suggested that persistent inward currents mediated by calcium channels mainly originate from dendrites. To date there are several morphological studies regarding the localization and distribution of CaV1.3 channels in spinal cord neurons from different species, but a comprehensive description of the distribution of CaV1.3 channels in the spinal cord has not been done. Recently, the members of our laboratory have dedicated to illustrate the distribution of CaV1.3 channels in different animal species including cat, rat and mouse under physiological conditions. From our published works on cat and rat we have demonstrated that CaV1.3 channels distribute in different kinds of neurons in the spinal cord and brain stem with more densely in the motoneurons, where they are mainly localized in cell somata and proximal dendrites. Our ongoing study on mouse shows that this channel distributes in a large extent in motoneuron dendrites including its distal dendrites besides in the cell somata. This may render some interesting discussions about the distribution differences in relation to the animal species and therefore differential physiological properties of related neurons.
Research direction II. Unravelling the molecular and cellular mechanisms of spasticity: expression changes of 5-HT receptors and intraspinal 5-HT neurons after spinal lesion
One other research interest of our laboratory is the gene expression changes of some ion channels, neurotransmitters and their receptors at mRNA and protein levels after spinalization. The purpose for these studies is to reveal some of the cellular and molecular mechanisms of spasticity which develops following spinal cord injury. Knowledge on the mechanisms responsible for these maladaptive plastic changes is of importance in relation to the understanding of the pathophysiology of spasticity and may provide important clues to its treatment. Although multiple mechanisms are involved, the enhanced persistent inward currents probably are one of the mechanisms behind the spasticity observed in the chronic spinalized rats. The expression of persistent inward currents in vertebrate motor neurons is regulated by neuromodulators / neurotransmitters such as serotonin (5-HT), noradrenalin, acetylcholine and glutamate. In the spinal cord 5-HT systems modulate the spinal network via various 5-HT receptors and play an important role in the recovery of motor function after spinal injury. Recently, using an in vitro preparation of the rat sacrocaudal spinal cord, Bennett and co-workers have demonstrated that the spinal motoneurons of chronically spinalized rats exhibit a 30-fold supersensitivity to 5-HT and this is mainly mediated by 5-HT2A/C receptors. In this project we will use this tail spasticity model to study the expression changes of 5-HT receptors (2A & C) and intraspinal 5-HT cells in the spinal cord below the lesion. In this project multiple neurobiological approaches will be used, which include real time reverse transcription PCR, in situ hybridization, immunohistochemistry, immuno-electron microscopy, in vitro motoneuron electrophysiology, and antisense oligodeoxynucleotide administration techniques. Thus far we have shown that 5-HT2A receptor is upregulated within 24 hours after spinalization and this upregulation can sustained for a quite long period.
Research group members:
Mengliang Zhang (Coordinator)
Hans Hultborn
Liqun Ren
Natalya Sukiasyan
