PI: Want, J.J.L. van der

University Medical Center Groningen

Previous and current research

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Principal Investigator: Dr Han J.L. van der Want

Synapses, their role during stress and development

The synapse is a microscopically small contact between neurons that conveys chemical signals from one neuron to the next. Stable neurochemical are fundamental features in neuronal connectivity. Synaptic plasticity is often associated with functional modifications during learning and development. Activity-dependent structural and functional interactions between neurons and their intimate glial-coating is not stable, but modifiable, which adds another layer of complexity in the function of neuronal circuits.

Purkinje cells are one of the largest neurons in the central nervous system, on their dendrites tiny protrusions, spines receive massive synaptic input. Dendritic spines are important sites of excitatory neurotransmission in the brain with their function determined by their structure and molecular content.

Alterations in spine number, morphology and receptor content are a hallmark of many psychiatric disorders, most notably those due to stress. We investigate the role of Corticotropin Releasing Factor (CRF) stress peptides on the plasticity of spines in the cerebellum, a structure implicated in a host of mental illnesses particularly of a developmental origin.  

We use organotypic slice cultures of the cerebellum and restraint stress in behaving animals to determine whether CRF in vitro and stress in vivo affects Purkinje cell spine density. Application of CRF and urocortin (UCN) to cerebellar slice cultures increase the density ofspines on PC signaling via CRF receptors (CRF-Rs) 1 & 2 and RhoA down regulation, although the structural phenotypes of the induced spines

Furthermore, CRF and UCN exert a trophic effect on the surface contact between synaptic elements by increasing active zones and postsynaptic densities and facilitating the alignment of pre- and postsynaptic membranes of synapses on PCs. In addition, one hour of restraint stress significantly increased PC spine density compared to those animals which were only handled. This recent study provides unprecedented resolution of CRF pathways which regulate the structural machinery essential for synaptic transmission and provides a basis for understanding stress-induced mental illnesses.


Projects

1. Role of PSA-NCAM during cerebellar development.

2. Expression of PSA-NCAM during chronic and short term stress in the cerebellum.

3. Ageing in Purkinje cells, expression of the aging gene Klotho.

4. Correlative technologies for combined light, fluorescent and electron microscopic analysis, including
     pre-embedding immunolabeling, lowicryl embedding for postembedding labeling and cryo-
    ultramicrotomy and immunogold labeling (Tokuyashi).

5. Training and supervision of new projects requiring microscopic analysis in the field of biological and
    medical sciences.  varies, suggesting that CRF-Rs differentially induce the outgrowth of functionally
    distinct populations of spines.  


Current International Collaborations:

New functions of synapses: Synaptic innervation of interneuron precursors directs their migration, Karl Schilling and Ronald Jabs, Department of Anatomy and Cell Biology and Institute of Cellular Sciences, University of Bonn, Bonn, Germany.

Corticotropin-releasing factor and urocortin regulate spine and synapse formation: structural basis for stress induced remodeling and pathology, Jerome Swinny, Institute of Biomedical Sciences, School of Pharmacy and Biomedical Sciences, University of Portsmouth, United Kingdom and Natasha Gounko, Scripps Research Institute, La Jolla, USA.

PSA-NCAM slippery molecule in neuronal growth and synaptic plasticity, Melitta Schachner, Zentrum fuer Molekulare Neurobiologie, Hamburg University Medical Center, Hamburg, Germany.



UMCG Microscopy and Imaging Center (UMIC)

Assists and performs light microscopy and electron microscopy in areas ranging from clinical diagnosis, protein imaging and material sciences.



Electron Microscopes - SEM, TEM, Supra  ( website ) - Intake form

Contact: Email: Jeroen Kuipers / cell: 06 1298 3675

High- end fluorescence microscopes ( website ) - Registration form

Contact: Email: Klaas Sjollema  /  cell: 06 5393 1741    

Last modified:October 30, 2013 13:01