ABSTRACT
Adult-born neurons adjust olfactory bulb (OB) network functioning in response to changing environmental conditions by the formation, retraction and/or stabilization of new synaptic contacts. While some changes in the odour environment are rapid, the synaptogenesis of adult-born neurons occurs over a longer time scale. It remains unknown how the bulbar network functions when rapid and persistent changes in environmental conditions occur but when new synapses have not been formed. Here we reveal a new form of structural remodelling where mature spines of adult-born but not early-born neurons relocate in an activity-dependent manner. Principal cell activity induces directional growth of spine head filopodia (SHF) followed by spine relocation. Principal cell-derived glutamate and BDNF regulate SHF motility and directional spine relocation, respectively; and spines with SHF are selectively preserved following sensory deprivation. Our three-dimensional model suggests that spine relocation allows fast reorganization of OB network with functional consequences for odour information processing.
Subject(s)
Dendritic Spines/physiology , Interneurons/physiology , Neurogenesis/physiology , Olfactory Bulb/physiology , Animals , Brain-Derived Neurotrophic Factor/genetics , Brain-Derived Neurotrophic Factor/metabolism , Cell Movement/physiology , Female , Glutamic Acid/metabolism , Image Processing, Computer-Assisted , Interneurons/cytology , Male , Mice , Mice, Inbred C57BL , Mice, Transgenic , Models, Animal , Models, Biological , Odorants , Olfactory Bulb/cytology , Pseudopodia/physiology , Sensory Deprivation/physiology , Smell/physiology , Synapses/physiology , Time-Lapse Imaging/methodsABSTRACT
Neuronal migration is one of the fundamental processes underlying the proper assembly and function of neural circuitry. The majority of neuronal precursors are generated far away from their sites of integration and need to migrate substantial distances to reach their final destination. Neuronal migration occurs not only in the embryonic brain but also in a few regions of the adult brain such as the olfactory bulb (OB). The mechanisms orchestrating cell migration in the adult brain are, however, poorly understood, despite their clinical relevance. Here we describe a method for time-lapse imaging of cell migration in acute brain slices. This method, combined with genetic and/or pharmacological manipulations of different molecular pathways, makes it possible to determine the dynamics and molecular mechanisms of cell migration in the adult brain. In addition, time-lapse imaging in acute brain slices makes it possible to monitor cell movement in a microenvironment that closely resembles in vivo conditions and to study neuroblast displacement along with other cellular elements such as astrocytes and blood vessels.
