Rescuing deficits in neuronal plasticity after mild TBI
Barclay Morrison III, Columbia University, USA
Traumatic brain injury (TBI) continues to be a major socio-economic problem with about 2 million head injuries in the US annually, the majority being mild in severity.To understand better the mechanisms of TBI, we have developed in vitro models using organotypic brain slice cultures that afford precise control over injury biomechanics.With these models, we have previously developed tolerance criteria to determine safe levels of exposure that could be used to engineer better safety systems to prevent TBI.More recently, we have focused on how different mechanical stimuli (injury) may alter neuronal activity and electrophysiological function within hippocampal neuronal networks and explored therapeutic strategies to reverse pathological changes.Our recent findings suggest that after mild TBI, a disruption of dendritic organization may underlie deficits in long-term potentiation, i.e. the cellular correlates of learning and memory.We have identified therapeutic interventions that rescue LTP with therapeutic windows as long as 6 hours after injury.The long-term goal of our research is to reduce the socio-economic costs of TBI by developing novel treatments and by helping others engineer better protection systems.
Vendredi 28 avril 2017 à 11h30, Salle de conférence.
The Unexpected Role of Ligand Number in Specific Ion Binding
Susan Rempe, Sandia National Laboratories, Albuquerque, NM, USA
Mardi 9 mai 2017 à 11h, Salle de réunion UMR8601.
Cancer colorectal et alimentation : les défenses anti-oxydantes dans la balance?
Laurence Huc, UMR INRA 1331 ToxAlim, Toulouse, France
Jeudi 11 mai 2017 à 11h, Salle de conférence.
Probing neural circuits with shaped light
Na Ji (Janelia Research Campus, USA)
To understand computation in the brain, one needs to understand the input-output relationships for neural circuits and the anatomical and functional relationships between individual neurons therein. Optical microscopy has emerged as an ideal tool in this quest, as it is capable of recording the activity of neurons distributed over millimeter dimensions with sub-micron spatial resolution. I will describe how we use concepts in astronomy and optics to develop next-generation microscopy methods for imaging neural circuits at higher resolution, greater depth, and faster speed. By shaping the wavefront of the light, we have achieved synapse-level spatial resolution through the entire depth of primary visual cortex, optimized microendoscopes for imaging deeply buried nuclei, and developed a video-rate (30 Hz) volumetric imaging method. We apply these methods to understanding neural circuits, using the mouse primary visual cortex as our model system.
Vendredi 19 mai 2017 à 11h30, Salle de conférence.
Localization of Synaptic Sites of Cortical Plasticity by MRI
Alan P. Koretsky, Laboratory of Functional and Molecular Imaging, NINDS, NIH, Bethesda, MD
Functional MRI techniques have found widespread use to measure brain neural circuits that are used for a large number of behaviors. When circuit activity changes due to plasticity, it remains a challenge to identify sites of synaptic changes responsible for the circuit level changes measured.Of particular interest are the cases of long range cortical rearrangements that have been detected in the human brain after injury.Rodent models that mimic some of these cortical rearrangements have been developed and are being used to determine the synaptic basis for the plasticity detected. We have developed a model of adult cortical plasticity due to peripheral somatosensory nerve damage that is being used to develop MRI tools that can pinpoint sites of synaptic changes.Two weeks after peripheral denervation of one side of the forepaw, hindpaw, or whisker pathway there is a large up-regulation of cortical activity from the spared side and a large up-regulation of callosal inputs from the spared cortex to the cortical representation of the denervated area.A combination of functional MRI and laminar specific neural track tracing using manganese enhanced MRI predicted changes in thalamo-cortical inputs to layer IV that contribute to the up-regulation of cortical activity along the spared whisker barrel pathway. Slice electrophysiology confirmed that the thalamic inputs on layer IV stellate cells were strengthened by a post-synaptic mechanism.Interestingly this plasticity was caused by reopening of LTP using a silent synapse mechanism. Sites of plasticity that explain the up-regulation of the callosal communication have also been studied with MRI and slice electrophysiology.High temporal-spatial resolution fMRI demonstrates that up-regulation of the communication between the spared and denervated cortices likely occur through callosal inputs. These fMRI results were consistent with manganese enhanced MRI that predicts a strengthening of inputs into layer 2/3 and 5.Slice electrophysiology verified a large up regulation of callosal inputs into layer 5 pyramidal neurons.Taken together these results demonstrate that MRI is positioned to begin to give laminar specific information about mechanisms of cortical plasticity.
Vendredi 9 juin 2017 à 11h30, Salle de conférence.