Vittori, Claudia Giulia.
Structural plasticity at the input stage of the adult cerebellar cortex.
PhD Thesis, University of Basel,
Faculty of Science.
Official URL: http://edoc.unibas.ch/diss/DissB_8666
In the last decades, a growing amount of evidence has showed that the adult brain is capable of undergoing dramatic reorganisation: learning new skills or acquiring novel experiences determine brain responses in order to reflect the changing circumstances. Changes in behaviour and brain function are probably accompanied by structural alterations in neuronal cells: while extensive descriptions of local rearrangements driven by experience during postnatal development have been provided, the adult brain was classically described to be resistant to such structural modifications. Nevertheless, recent studies convincingly showed that the adult brain is able not only to adapt synaptic transmission, but also to undergo remodelling of pre- and postsynaptic compartments in response to experience. Plasticity phenomena have been generally described for either pre- or postsynaptic compartments within small cortical fields, thus not fully clarifying the influence of structural remodelling on the synaptic transmission, on the neuronal behaviour (e.g. global versus local behaviour of a given axonal projection) and, lastly, on the circuit connectivity. In addition, considerable effort is currently made in order to establish a causal relationship between synaptic, structural and representational or topographic map plasticity. In order to address, at least in part, these questions, we exploited the simple and well-characterized cerebellar circuitry: this system has long been known as a centre for fine motor control and sensorymotor integration; moreover, in the past decade, new results have suggested an involvement of the cerebellum in cognitive and emotional functions. In addition, the cerebellum is a brain region endowed with a high degree of structural plasticity during development, as well as in the adulthood, not only following damage, but also in order to maintain its normal architecture under the influence of activity. The cerebellar anatomy is characterized by a simple and stereotyped connectivity between readily identifiable neurons, and therefore allows the investigation of synaptic rearrangements on a comprehensive scale. We focused our attention on the input stage of the vermal lobule V, namely at the synapse between mossy fiber (MF) terminals and granule cell (GC) dendrites. MF axons convey multimodal sensory information from distinct sources, such as spinal cord, vestibular system and cerebral cortex. The physiological properties and the anatomical arrangement at this stage, make the MF-GC synapse an advantageous system to investigate pre- and postsynaptic structural plasticity induced by experience. Here, we used two distinct behavioural paradigms: in one case, mice were housed in an enriched environment (EE), in order to provide social interactions and extensive sensorymotor stimulation. In a second set of experiments, mice were trained to associate a neutral stimulus with an aversive one, exploiting a pavlovian learning paradigm that relies on fear emotion (fear conditioning, FC). We combined these tasks with large-scale confocal imaging in transgenic mouse lines that express membrane-targeted GFP in few neuronal cells, thus revealing their morphology in crisp details. This approach allowed us to solve and analyze entire MF projections, and related presynaptic terminals, as well as GC dendritic compartments. In general, we found that distinct experiences elicit substantially different remodelling events, in terms of structural outcome and time course. Upon EE, the MF-GC connectivity is profoundly altered in the properties of the afferent projections and in the putative amplification and transmission of the sensory information. The refinement of the connectivity (i.e. the number of presynaptic inputs per cell) is particularly altered in animals that were reared since birth in the enriched context; but a similar robust remodelling of single synaptic units (i.e. the dendritic endings) also occured in animals that experienced EE only in the adulthood. We further found that FC triggers a stepwise remodelling of the local connectivity at the MF-GC synapse, which proceeds for several days after the training and affects the whole population; the extent and quality of remodelling is lobule-specific and can be further modulated according to subsequent experience. The structural rearrangements we observed upon distinct experiences show that the adult cerebellar system is able to undergo extensive reshaping of its connectivity and synaptic organization. Complementary evidence about synaptic transmission at the MF-GC synapse upon EE and FC would help to assess a correlation between anatomical and functional properties.
|Committee Members:||Strata, Piergiorgio and Arber, Silvia|
|Faculties and Departments:||05 Faculty of Science > Departement Biozentrum > Neurobiology|
|Bibsysno:||Link to catalogue|
|Number of Pages:||166|
|Last Modified:||30 Jun 2016 10:41|
|Deposited On:||17 Jul 2009 09:26|
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