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Loewel, S.

Publications and source records attributed to Loewel, S..

3 recordsLinked to original sources

Bassoon is required for adult ocular dominance plasticity and experience-induced changes in synapsin phosphorylation in visual cortex

Sensory stimulation enables experience-dependent fine tuning of brain circuits for optimal perception. In juvenile mice, brief closure of the contralateral eye reduces primary visual cortex (V1) activation through the deprived eye. In contrast, in adult animals, eye closure induces potentiated V1-responses to non-deprived eye visual stimulation. While considerable knowledge exists about postsynaptic mechanisms underlying this ocular dominance (OD) plasticity, little is known about contributing presynaptic molecules. Here we report that constitutive deletion of the presynaptic scaffolding protein bassoon (Bsn{Delta}Ex4/5) disrupted OD-plasticity in V1 of adult mice leaving juvenile OD-plasticity unaffected. Notably, in mice with a conditional deletion of Bsn only from cortical glutamatergic neurons (BsnEmx1), adult OD-plasticity was also impaired indicating that normal presynaptic plasticity of glutamatergic cortical synapses is selectively required in this process. While spatial vision was severely compromised in Bsn{Delta}Ex4/5 mice, it was preserved in BsnEmx1 mice, consistent with normal Bsn expression in subcortical circuit in these mice. Parallel experiments in cultured neurons revealed that deletion of Bsn left the inactivity-induced postsynaptic scaling of AMPA-responses mediated by increased AMPA receptor trafficking unchanged. However, presynaptic scaling was completely abolished as assessed by both electrophysiology and live-cell imaging of evoked synaptic vesicle fusion in cultured primary cortical neurons. Finally, monocular deprivation induced enhanced phosphorylation of synaptic vesicle-associated synapsin in contralateral V1 that was absent in BsnEmx1 mice. Overall, our data indicate that adult OD-plasticity requires Bsn-dependent presynaptic plasticity, involving experience-induced changes in synapsin phosphorylation. In contrast, juvenile OD-plasticity does not appear to be dependent on Bsn.

neuroscience↗

PSD-95 drives binocular vision maturation critical for predation

Postsynaptic density protein 95 (PSD-95) is a signalling scaffold within the postsynaptic density of excitatory synapses which drives silent synapse maturation during critical periods (CP). Binocularity develops during visual CPs and matures before its closure. Despite lifelong critical period plasticity, PSD-95 knock-out (KO) mice were reported with only subtle sensory phenotypes as adults. To assess PSD-95s role in ethologically relevant binocular visual processing, we compared prey capture behaviour in PSD-95 KO and wild-type (WT) mice. KO mice were profoundly impaired in diverse epochs of predatory behaviour, but exhibited improved prey localisation under monocular conditions, reminiscent of impaired binocular integration. This was confirmed in an orientation discrimination task, where KO mice were impaired binocularly but performed monocularly like WT mice. Furthermore, binocular orientation discrimination was impaired after knocking down PSD-95 in primary visual cortex (V1), while a superior colliculus-specific knock-down had no effect. These results support an essential role of PSD-95 in binocular behaviour, which becomes evident under ethologically demanding behaviours.

neuroscience↗

More running causes more ocular dominance plasticity in mouse primary visual cortex: new gated running wheel setup allows to quantify individual running behaviour of group-housed mice

Environmental enrichment boosts neuronal plasticity of standard-cage raised (SC) mice. Since it becomes increasingly more important to track individual mouse behaviours and its influence on brain plasticity, we designed a gated running wheel (gRW) setup allowing to correlate wheel running with neuronal plasticity, using the established paradigm of ocular dominance (OD)-plasticity after monocular deprivation (MD). After SC-rearing until adulthood (>P110), group-housed mice were transferred to gRW cages, that provided an additional running wheel compartment for tracking individual wheel activity via implanted RFID chips. Notably, individual running parameters varied enormously: mice ran from close to 0 to [~]20 km across the 7 days of gRW experience, with on average running 0-3.96 km in 0-3.85 h/d and running bouts lasting from <1 up to 10 min, while running at a speed of 6-26 cm/s. OD-plasticity in V1 after 7 days of MD in the gRW was visualized using intrinsic signal optical imaging, and compared to control gRW-mice without MD via calculation of an OD-index. Most, notably - while wheel running enabled OD-plasticity -individual running parameters correlated with individual OD-indices after MD: Mice running longer distances, for longer time, at higher speeds and with longer and more frequent bouts displayed more experience-dependent V1-plasticity. In turn, a composite measure of overall running wheel activity derived from principal component analysis of running parameters accounted for 65% of inter-individual variability of OD-index following MD. Together our study demonstrates that interindividual variability of running behaviour is high, and mice intrinsically motivated to run more show enhanced V1-plasticity, underscoring the huge importance of analysing individual behavioural parameters together with any measure of brain plasticity. End Graphical abstract With our newly developed gated running wheel setup, we observed a striking correlation between individual running activity, and a measure of experience dependent plasticity in mouse primary visual cortex. More running caused more plasticity: running speed, running distance, total running time, number of running bouts and bout duration all correlated with a measure of visual cortical plasticity, the ocular dominance index. Thus, our observations add to the growing body of evidence that individual behavioural choices strongly affect individual brain plasticity. O_FIG O_LINKSMALLFIG WIDTH=149 HEIGHT=200 SRC="FIGDIR/small/647197v2_ufig1.gif" ALT="Figure 1"> View larger version (21K): org.highwire.dtl.DTLVardef@e1045dorg.highwire.dtl.DTLVardef@e5af90org.highwire.dtl.DTLVardef@1693a46org.highwire.dtl.DTLVardef@170ec3d_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗