Show simple item record

Roles of PSD-93 and environmental enrichment in cortical synapses

dc.contributor.advisorSchlüter, Oliver Dr. Dr.
dc.contributor.authorDas Neves Favaro, Plinio
dc.titleRoles of PSD-93 and environmental enrichment in cortical synapsesde
dc.contributor.refereeStühmer, Walter Prof. Dr.
dc.description.abstractengDuring neurodevelopment several structural, molecular and functional changes take place in the brain to promote its maturation. These changes occur at multiple levels, including changes in protein expression, in the strength of synaptic transmission and in the susceptibility to experience-driven plasticity. In the present study, using whole-cell patch-clamp electrophysiology, I examined the roles of PSD-93, a postsynaptic scaffolding protein, in the developmental profile of cortical glutamatergic synapses, in the strength of basal neurotransmission and in the mechanisms of synaptic plasticity. Furthermore, I analyzed how exposure to an enriched environment (EE), with enhanced physical, social and cognitive stimulation, affects both excitatory and inhibitory neurotransmission in the visual cortex of mice. My results show that, in visual cortex, the normal maturation of glutamatergic neurotransmission was characterized by a robust reduction in the fraction of AMPAR-lacking synapses (silent synapses): from 80% at Postnatal days 3-5 (PD3-5), to about 50% at PD10-12 and further to 25% at PD21-30. PSD-93 deletion caused accelerated synaptic maturation. The percentage of silent synapses was precociously decreased at PD10-12 (30%), and also at PD21-30 (0%). In depth electrophysiological analysis revealed that this accelerated synaptic maturation, represented by absence of silent synapses at PD21-30, caused a functional increase in the strength of postsynaptic AMPAR neurotransmission, while basal NMDAR function remained normal. In contrast, PSD-95 deletion prevented synaptic maturation after PD10-12, so the fraction of silent synapses stayed high at PD21-30 (about 50%). Direct comparison of PSD-93 and PSD-95, by simultaneous deletion of both proteins, revealed that the fraction of silent synapses remained indistinguishable from Control at PD21-30. Thus, the present study reveals a novel scenario in which PSD-93 and PSD-95 present opposite roles governing the maturation of glutamatergic neurotransmission. Furthermore, PSD-93 deletion did not affect basal NMDARs, but impaired NMDAR-dependent LTD, converting it into LTP. This suggests PSD-93 involvement in coupling NMDAR activity to downstream signaling mechanisms related to synaptic plasticity. Taken together, these results expand the knowledge about the molecular mechanisms underlying synaptic maturation in visual cortex; and enrich the current view concerning the roles of PSD-93 and its functional interactions regulating synaptic transmission and plasticity. Concerning EE, it was previously shown that it can increase experience-driven plasticity in the visual cortex, using ocular dominance plasticity (ODP) as a model. Essentially, ODP gradually declines and is absent beyond PD110. However, if mice are raised in EE, ODP is preserved throughout adulthood beyond PD130. In this context, my results show that, beyond PD130, EE mice presented reduced intracortical inhibition when compared to age-matched controls. Furthermore, inhibition levels in old EE mice were indistinguishable from the inhibition levels observed in young mice at PD21-30. Additional results from our collaborators evidenced that the preserved ODP in old EE mice was almost totally abolished by pharmacological boosting of inhibitory neurotransmission. Thus, the gradual reduction in experience-driven cortical plasticity can be prevented by exposing mice to an enriched environment with enhanced physical, social and cognitive stimulation. The present data show that modulation of intracortical inhibition, by environmental stimulation, plays a key role in this
dc.contributor.coRefereeTaschenberger, Holger Dr.
dc.contributor.thirdRefereeLöwel, Siegrid Prof. Dr.
dc.contributor.thirdRefereeHörner, Michael Prof. Dr.
dc.subject.engVisual Cortexde
dc.affiliation.instituteGöttinger Graduiertenschule für Neurowissenschaften, Biophysik und molekulare Biowissenschaften (GGNB)de
dc.subject.gokfullBiologie (PPN619462639)de

Files in this item


This item appears in the following Collection(s)

Show simple item record