Research Article: Remodeling the Dendritic Spines in the Hindlimb Representation of the Sensory Cortex after Spinal Cord Hemisection in Mice

Date Published: July 1, 2015

Publisher: Public Library of Science

Author(s): Kexue Zhang, Jinhui Zhang, Yanmei Zhou, Chao Chen, Wei Li, Lei Ma, Licheng Zhang, Jingxin Zhao, Wenbiao Gan, Lihai Zhang, Peifu Tang, Xiangming Zha.

http://doi.org/10.1371/journal.pone.0132077

Abstract

Spinal cord injury (SCI) can induce remodeling of multiple levels of the cerebral cortex system especially in the sensory cortex. The aim of this study was to assess, in vivo and bilaterally, the remodeling of dendritic spines in the hindlimb representation of the sensory cortex after spinal cord hemisection. Thy1-YFP transgenic mice were randomly divided into the control group and the SCI group, and the spinal vertebral plates (T11–T12) of all mice were excised. Next, the left hemisphere of the spinal cord (T12) was hemisected in the SCI group. The hindlimb representations of the sensory cortex in both groups were imaged bilaterally on the day before (0d), and three days (3d), two weeks (2w), and one month (1m) after the SCI. The rates of stable, newly formed, and eliminated spines were calculated by comparing images of individual dendritic spine in the same areas at different time points. In comparison to the control group, the rate of newly formed spines in the contralateral sensory cortex of the SCI group increased at three days and two weeks after injury. The rates of eliminated spines in the bilateral sensory cortices increased and the rate of stable spines in the bilateral cortices declined at two weeks and one month. From three days to two weeks, the stable rates of bilaterally stable spines in the SCI group decreased. In comparison to the control group and contralateral cortex in the SCI group, the re-emerging rate of eliminated spines in ipsilateral cortex of the SCI group decreased significantly. The stable rates of newly formed spines in bilateral cortices of the SCI group decreased from two weeks to one month. We found that the remodeling in the hindlimb representation of the sensory cortex after spinal cord hemisection occurred bilaterally. This remodeling included eliminating spines and forming new spines, as well as changing the reorganized regions of the brain cortex after the SCI over time. Soon after the SCI, the cortex was remodeled by increasing spine formation in the contralateral cortex. Then it was remodeled prominently by eliminating spines of bilateral cortices. Spinal cord hemisection also caused traditional stable spines to become unstable and led the eliminated spines even more hard to recur especially in the ipsilateral cortex of the SCI group. In addition, it also made the new formed spines unstable.

Partial Text

Spinal cord injury (SCI) dramatically alters sensory and motor functions by seriously blocking the normal function of sensory inputs and motor outputs between the brain and the body [1–3]. Significant changes occur in the way in which the relevant sensory cortex receives sensory inputs from the body after SCI [4]. In addition to the direct loss of motor and sensory functions, SCI can induce massive long-term remodeling of the brain up to the relevant motor and sensory cortices [1,5–7]. Long-term cortical reorganization may lead to a certain amount of recovery on selective motor and sensory functions. However, maladaptive or abnormal reorganization can induce illusory sensations that do not reflect objective reality, such as neuropathic pain [8–11], hyperpathia, and phantom sensations [5].

Structural remodeling at the level of individual synapses may be the underling mechanism of remodeling after the SCI. Understanding the mechanism is important for performing efficient and timely interventions to modulate the pathological and physiological consequences of SCI and to achieve the best recovery outcomes [6,7]. To determine whether SCI leads to bilateral synaptic alterations in the sensory cortex after spinal cord hemisection, we used transcranial two-photon microscopy (thinned skull protocol) and transgenic mice that express YFP predominantly in the layer V pyramidal neurons. We repeatedly imaged individual dendritic branche and spine in the hindlimb sensory cortex after the SCI. We found that remodeling the hindlimb representation of the sensory cortex following spinal cord hemisection occurred bilaterally. This type of remodeling included both eliminating and forming spines simultaneously, and the regions of reorganization in the cortex after the SCI changed over time. The rate of newly formed spines in the contralateral cortex at three days after injury was higher than those of the control group and the ipsilateral cortex in the SCI group. These results demonstrated that soon after the SCI, spine remodeling was performed by increasing spine formation in the contralateral cortex. At two weeks after the SCI, remodeling occurred by increasing both the spine formation and elimination in the contralateral cortex and increasing the spine elimination of the ipsilateral cortex. At the same time, stable spines in bilateral cortices decreased in the SCI group. After that, the remodeling occurred by increasing spine elimination but not spine formation in the bilateral cortices. Synaptic eliminations and formations after the SCI may be critical events for reshaping the dysfunctional cortical connections [29]. From three days to two weeks, the stable rates of bilaterally stable spines in the SCI group decreased. Compared to the control group and the contralateral cortex in the SCI group, the re-emerging rate of eliminated spines in ipsilateral cortex decreased significantly. From two weeks to one month, the stable rates of formed spine in bilateral cortices of the SCI group decreased. These results means that in the early time, spinal cord hemisection made traditional stable spines unstable and led the eliminated spine even more hard to recur especially in the ipsilateral cortex. And it also made the newly formed spines unstable. The low stability of spines may suggest a shrinkage in the structural foundation for information storage, and the plasticity of the dendritic spines offers the cortex the capability to rewire the cortical circuits in response to alternative experiences [45]. The dynamic modulation of the density of spines might indicate that the functional and physiological properties in the sensory cortical circuits are significantly changed by SCI [24]. Such results demonstrate the significant changes that occur in the dendritic spines after SCI and suggest that changes in the inputs to axotomized corticospinal neurons indeed contribute to changes in the cortical hardware of dendritic dendrites [46].

 

Source:

http://doi.org/10.1371/journal.pone.0132077