CRASCI · Spatial-temporal characteristics of Cortical Reorganization after Spinal Cord Injury and the role of interneurons and astrocytes
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2018-08-01 → 2021-04-20
- EU contribution
- €170,122
- Participants
- 1
- Scheme
- MSCA-IF-EF-SE
Lines connect the coordinator with its partners.
Results in brief
Spatial-temporal characteristics of Cortical Reorganization after Spinal Cord Injury and the role of interneurons and astrocytes
Problem Spinal cord injury (SCI) is a damage to the spinal cord that causes temporary or permanent changes in strength, sensation and other autonomic functions in body parts below the injury level. In addition, SCI also affects brain activity as it interrupts the sensory information flow from the periphery to the somatosensory cortex (S1, brain region responsible to receive and interpret the information from the world to generate an output behaviour). The loss of incoming signals to the brain initiates a process of plasticity (reconnection between neurons) called cortical reorganization (CoRe), in which neuronal activity from adjacent, intact brain regions increases and expands towards the affected area. CoRe is crucial for the functional recovery of SCI patients, but when exacerbated can trigger pathologies such as neurophatic pain, phantom sensation and spasticity that drastically decrease the quality life of the patients. Therefore, knowing the mechanisms by which CoRe occurs in time is key to generate new therapeutic strategies to promote and/or limit the extension of the reorganization following SCI and other traumatic brain injuries. Societal Impact The SCI is one of the most important worldwide causes of death and disability affecting patients, relatives, caretakers and the society. In 2016, ~0.93 million of new SCI cases were addressed, with ~27.04 millions of prevalent cases. The estimated average annual burden is very high with an annual cost for the 1st year between EUR 92k and 212k in Spain. Nowadays there is no cure or treatment for SCI. Therefore, the number of patients is always increasing becoming a public health problem worldwide. In the last decade, new neuromodulation techniques applied to the brain have revolutionized the SCI field, showing that directly modulation of brain activity can trigger new spontaneous neuronal connections in the spinal cord to promote locomotion and can be used to treat secondary pathologies associated with the lesion. Therefore, a deep spatial-temporal characterization of the changes in brain activity and the cellular components underlying such alterations is utterly important to improve and/or generate new therapeutic protocols. By interconnecting two prominent fields in physiology research, system neuroscience and neuronal network, the findings emerging from this MSCA project offer promising outcomes for brain injuries with direct impact on both the society and the scientific community. CRASCI overall objectives CRASCI focused on the study of the mechanisms controlling/limiting the extension of the cortical reorganization after SCI. To do that, the multidisciplinary project had three main objectives: (i) an in-depth S1 layering characterization of the CoRe at distinct time points after SCI, (ii) to investigate how reorganisation following SCI changes the activity of inhibitory interneurons and (iii) to study the role of astrocytes in modulating somatosensory CoRe. Conclusions of the Action CRASCI was completed according to the proposed plan in Annex I, without major deviations. The achievements within the Project were: 1.The characterization of the overall physiological phenomena of CoRe across layers and the role of astrocytes in controlling the strength of the corticocortical connections responsible to such process. 2.The development and the implementation of new techniques to study in vivo the role of neuron-astrocyte interaction in triggering neuronal plasticity. 3.Successful integration of the MSCA fellow at the Host, fulfilment of the training objectives (i.e. new scientific, communication and teaching skills, scientific leadership, management and increased scientific network) and accomplishment of the two way transfer of knowledge between the researcher and the Host lab/institution. 4.The MSCA fellow successfully achieved a Career Development Plan that ultimately led to a Tenured-Track position as an independent researcher (Ramon y Cajal Program Researcher) at the Host Institution.
Data: CORDIS, © European Union
Project objective
Spinal cord injury (SCI) is followed by functional reorganization of the primary somatosensory cortex (S1), in which the S1 area deprived of inputs is activated by sensory stimulation of surrounding intact regions. Recent data suggest that reorganization after SCI is a heterogeneous process depending on the time elapsed after injury and the cortical layer under study. This research proposal aims to study the complexity of the cortical reorganization after SCI in terms of spatial-temporal patterns and the involvement of distinct cell types as inhibitory interneurons and astrocytes. This will be achieved by monitoring and manipulating brain activity using in vivo and in vitro electrophysiology, genetically encoded calcium indicators (GCaMP6), chemogenetics (DREADDs) and transgenic mice. A mice model of thoracic SCI will be used throughout the study. First, reorganization of the hindlimb and forelimb S1 cortex at different time points after the injury will be studied by recording in vivo neuronal activity in response to sensory stimulation across all layers of S1 using a vertical multielectrode array. Second, changes in inhibitory transmission induced by SCI will be studied by monitoring intracellular Ca2+ signaling and by in vitro electrophysiology from GFP expressing GABAergic cells. Third, the role of astrocytes in the reorganization after SCI will be studied by using either Gq DREADD to enhance astrocyte activity or IP2R2-/- mice to decrease astrocyte activity while recording in vivo neuronal responses across all layers of S1. Changes in astrocyte activity after SCI will also be determined by monitoring intracellular Ca2+ signals from astrocytes expressing the calcium indicator GCaMP6. Results from this proposal will be a first in understanding the complex network of local plasticity in S1 both in control conditions and after SCI. It will be also relevant to design new therapies for SCI-associated pathologies as neuropathic pain.
Original text from CORDIS.
Participants
- FUNDACION HOSPITAL NACIONAL DE PARAPLEJICOS · ToledoCoordinatorSpain
Links
Data: CORDIS, © European Union
