| dc.description.abstracteng | Bassoon mutant mice (Bsn-/-) display a striking loss of synaptic ribbons in photoreceptor terminals, which impairs signal transduction through the retina (Altrock et al., 2003; Specht et al., 2007). Therefore we assessed vision in these mice behaviorally with the virtual-reality optomotor system (Prusky et al., 2004) and the visual water task (Prusky et al., 2000). In addition, we performed in vivo optical imaging of intrinsic signals (Kalatsky and Stryker, 2003). Our behavioral tests revealed that visual acuity, contrast sensitivity, and temporal resolution were significantly reduced in mutants compared to littermate controls, whereas the time course of visual development was not altered in Bsn-/- mice compared to their littermates. Optical imaging of visual cortical activity revealed no differences between Bsn-/- and Bsn+/+ mice, both magnitude of visual responses and quality of retinotopic maps were similar, which we interpret as evidence for the presence of homeostatic mechanisms (Turrigiano and Nelson, 2004). In short, these results show that decent visual performance can be achieved in spite of impaired signal transfer at photoreceptor ribbon synapses.
Since Bsn-/- mice have a modified excitation-inhibition-balance and inhibition plays a major role in ocular dominance (OD) plasticity (Hensch et al., 1998), we studied whether Bsn-/- mice display modified OD plasticity and/or interocular plasticity, in which monocular deprivation (MD) leads to enhanced optokinetic responses selectively through the open eye (Prusky et al., 2006). In order to achieve this we i) visualized cortical activity maps in the visual cortex (V1) of both Bsn+/+ and Bsn-/- juvenile mice after four days and in adult mice after seven days of MD using optical imaging of intrinsic signals, and ii) measured visual acuity and contrast sensitivity of the open eye in the virtual-reality optomotor system for both groups. While there was a significant change in the OD after MD in juvenile Bsn-/- mice, OD plasticity was absent in adults in contrast to their wild-type littermates. In juvenile and adult Bsn-/- mice sensory improvement was significantly reduced compared to Bsn+/+ littermates.
It was previously shown that adult Bsn-/- mice display an increased number of parvalbumin positive interneurons in the striatum (Ghiglieri et al., 2009) and increased inhibition could be one explanation for the absent OD plasticity of our adult Bsn-/- mice, therefore we performed immunohistochemistry for parvalbumin in the visual cortex. We observed that the number of parvalbumin positive interneurons was increased in the visual cortex of Bsn-/- mice. The reduced plasticity is most likely due to morphological changes like the increased number of inhibitory parvalbumin positive neurons based on the mutation of Bassoon as well as to alterations due to the increasing frequency of epileptiform seizures (Altrock et al., 2003; Ghiglieri et al., 2009). Taken together, our data indicate that there is loss of OD plasticity after MD in adult Bsn-/- mice and impairment in interocular plasticity after MD in juvenile as well as adult Bsn / mice.
To test the role of the postsynaptic density protein 95 (PSD-95) in V1 of mice, we visualized activity of V1 using intrinsic signal optical imaging in PSD-95 knockout (KO) mice (Yao et al., 2004), in wild-type (WT) as well as in heterozygous littermates (HZ) and also measured their visual performance behaviorally. Both visual acuity and contrast sensitivity were only slightly but significantly reduced in PSD-95 KO mice compared to WT/HZ mice. Additionally, we found that optical imaging of V1 activity revealed that the magnitude of optical responses of elevation maps was significantly higher in PSD-95 KO mice, whereas the magnitude of the optical responses of azimuth maps as well as map scatter of both elevation and azimuth maps were indistinguishable from WT/HZ mice.
PSD-95 KO animals show altered hippocampal synaptic plasticity (enhanced long-term potentiation, diminished long-term depression), most likely due to an increased number of AMPA silent synapses, which was also observed in V1 by our cooperating group (Schlüter, Huang from the ENI, Germany) (Huang et al., 2012). Therefore we tested OD plasticity and interocular plasticity of PSD-95 KO mice and their WT/HZ littermates. During MD the improvement of visual acuity and contrast sensitivity through the open eye was similar in PSD-95 KO and WT/HZ mice showing preserved interocular plasticity. In PSD-95 KO mice, juvenile OD plasticity was found in animals of all ages (until postnatal day 507) at which the OD shift was mediated by a significant decrease of deprived-eye responses in V1. To test if the prolonged phase of plasticity of PSD-95 KO mice was due to reduced intracortical inhibition (Hensch et al., 1998) we treated mice during seven days of MD with a dosage of diazepam that reliably blocked OD plasticity in adult WT/HZ mice. Interestingly, diazepam treatment did neither reduce OD plasticity nor interocular plasticity in PSD-95 KO mice compared to WT/HZ mice. Taken together, these results clearly suggest that the preserved OD plasticity in older mice is not caused by changes in the inhibitory tone but rather by a higher number of AMPA silent synapses. | de |