Sofia Cristina Soares de Morais Grade - LMU/Helmholtz Zentrum, Munich
Title: Local environment determines integration of transplanted neurons
Abstract:
Cell transplantation aiming at replacing neurons lost upon brain injury or disease has been pursued, however, it remained elusive whether transplanted neurons can faithfully wire into mature circuits.
We induced selective cell death in the primary visual cortex (V1) of adult mice, a confined and noninflammatory injury, and transplanted neurons from the embryonic mouse neocortex. We demonstrate that neurons acquire mature morphologies, extend axons to correct targets through the host parenchyma, and develop synaptic specializations. Using rabies virus-based monosynaptic tracing we show that they receive area-specific, afferent projections matching those of endogenous V1 neurons, including topographically organized geniculate-cortical (graft) connections. Next, we compared neuronal integration in different environments: a traumatic invasive brain injury and the intact cerebral cortex. Transsynaptic tracing after transplantation into the stab wound injured cerebral cortex reveals a V1-specific connectome with no aberrant afferent areas, but an excess of local input. Conversely, neurons transplanted in the intact brain receive correct but considerably fewer connections per cell. Altogether our data indicate that neurons can integrate with great specificity into adult neocortical circuits, a central question for functional reconstruction of the brain, and pinpoint a key role for the local environment critically affecting the synaptic integration into host neuronal networks.
Title: Local environment determines integration of transplanted neurons
Abstract:
Cell transplantation aiming at replacing neurons lost upon brain injury or disease has been pursued, however, it remained elusive whether transplanted neurons can faithfully wire into mature circuits.
We induced selective cell death in the primary visual cortex (V1) of adult mice, a confined and noninflammatory injury, and transplanted neurons from the embryonic mouse neocortex. We demonstrate that neurons acquire mature morphologies, extend axons to correct targets through the host parenchyma, and develop synaptic specializations. Using rabies virus-based monosynaptic tracing we show that they receive area-specific, afferent projections matching those of endogenous V1 neurons, including topographically organized geniculate-cortical (graft) connections. Next, we compared neuronal integration in different environments: a traumatic invasive brain injury and the intact cerebral cortex. Transsynaptic tracing after transplantation into the stab wound injured cerebral cortex reveals a V1-specific connectome with no aberrant afferent areas, but an excess of local input. Conversely, neurons transplanted in the intact brain receive correct but considerably fewer connections per cell. Altogether our data indicate that neurons can integrate with great specificity into adult neocortical circuits, a central question for functional reconstruction of the brain, and pinpoint a key role for the local environment critically affecting the synaptic integration into host neuronal networks.