The role of synaptopodin, the spine apparatus and the axonal cisternal organelle in activity-dependent synaptic and network plasticity in the dentate gyrus
Final Report Abstract
The function of the spine apparatus in dendritic spines and the cisternal organelles in axon initial segments is little understood. The actin-associated protein, synaptopodin, is essential for the formation of these organelles which are absent in synaptopodin -/- mice. In this project we used synaptopodin KO mice to explore the role of the spine apparatus and the cisternal organelle in synaptic plasticity and local circuit excitability in response to activation of the perforant path input to the dentate gyrus in vivo. We found impaired long-term potentiation following theta-burst stimulation, whereas tetanus-evoked LTP was unaffected. Furthermore, paired-pulse inhibition of the population spike was reduced and granule cell excitability was enhanced in mutants, hence revealing an impairment of local network inhibition. In summary, our data represent the first electrophysiological evidence that the lack of the spine apparatus and the cisternal organelle leads to a defect in long-term synaptic plasticity and alterations in local circuit control of granule cell excitability under adult in vivo conditions. To determine further molecular players involved in the regulation of the excitability and GABAergic inhibition in the dentate gyrus network in vivo, we investigated granule cell function in anesthetized betaIV-spectrin mutant and collybistin-deficient mice after electrical stimulation of the perforant path in vivo. In summary, our findings indicate that synaptopodin, betaIV-spectrin and collybistin are involved in the network excitability in the mouse dentate gyrus in vivo.
Publications
- (2008) A role for the spine apparatus in LTP and spatial learning. Behav Brain Res 192:12-19
Jedlicka P, Vlachos A, Schwarzacher SW, Deller T
- (2008) Just in time for late-LTP: A mechanism for the role of PKMzeta in long-term memory. Communicative & Integrative Biology 1: 190 -191
Vlachos A, Maggio N, Jedlicka P
- (2009) Impaired in vivo LTP and network excitability in the dentate gyrus of synaptopodin-deficient mice lacking the spine apparatus and the cisternal organelle. Hippocampus, 19:130-140
Jedlicka P, Schwarzacher SW, Winkels R, Kienzler F, Frotscher M, Bramham CR, Schultz C, Bas Orth C, Deller T
- (2009) Reduced excitability in the dentate gyrus network of betaIV-spectrin mutant mice in vivo. Hippocampus, 19:677-86
Winkels R, Jedlicka P, Jedlicka P, Weise F, Schultz C, Deller T, Schwarzacher SW
- ncreased network excitability and impaired induction of long-term potentiation in the dentate gyrus of collybistin-deficient mice in vivo (2009) Molecular and Cellular Neuroscience, 41:94-100
Jedlicka P, Papadopoulos T, Deller T, Betz H, Schwarzacher SW
