Enhancing visual cortical plasticity in mice by enriching their environment: a combined imaging and behavioural study

Brain plasticity is important not only for normal brain functions like learning and memory, but is also crucial for recovery after injuries. It has been shown that the environment has a great influence on brain plasticity. Here, I investigate the impact of an enriched environment (EE) on ocular dominance (OD) plasticity of the mouse primary visual cortex (V1), using monocular deprivation (MD) as a model to trigger OD-plasticity and optical imaging of intrinsic signals to monitor it. Additionally, a variety of behavioural tests was used to measure the visual abilities of mice and their alteration after MD. OD-plasticity in V1 is an age-depended phenomenon: it is maximal during the critical period (postnatal day (PD) 21-35), reduced but still present in young adult mice (2-3 months) and absent in fully mature animals (beyond PD110). This age dependence holds true for mice raised in standard cages (SC), however we showed that raising mice in a more complex environment could not only prolong the sensitive phase for OD-plasticity into adulthood but also reinduce OD-plasticity in mice transferred to EE after PD110. Interestingly, the observed OD-plasticity in old EE-mice was similar to that in SC-mice during the critical period, suggesting that EE-housing resulted in a more juvenile brain. Additionally, we found that EE-raising can enable even lifelong OD-plasticity (up to PD900). Using behavioural tests we also showed that EE-raising did not affect the visual abilities of old mice and did not increase the interindividual variability. To test whether OD-plasticity in adult EE-mice is indeed juvenile-like, we tested different age groups of EE-mice after 4 days of MD. We found that 4 days of MD can induce an OD-shift in all the age groups of EE-mice tested, but the OD-shift in young and fully mature EE-mice was similar to adult OD-plasticity observed in around 3 month old SC-mice. EE-raising provides mice with increased social interactions, physical exercise and cognitive stimulation compared to SC rearing. We asked the question, whether all components are needed or just one of them is already sufficient to prolong OD-plasticity. We tested whether voluntary physical exercise alone prolongs OD-plasticity by raising mice in SCs equipped with a running wheel (RW). RW-raised mice continued to show an OD-plasticity into adulthood, while mice without a RW did not. Moreover, running only for 7 days was sufficient to restored OD-plasticity in adult SC-raised mice. In addition, the OD-shift of RW-mice was mediated by a decrease in deprived eye responses, which was previously seen only in critical period SC-mice or in adult EE-mice. It was previously shown, that a small lesion in the primary somatosensory cortex (S1) prevented both cortical plasticity and improvement of visual abilities in the adult mouse visual system after MD. However, in adult EE-mice, OD-plasticity was preserved after stroke induction and the improvement of visual abilities was partially preserved. Here, we investigated, whether raising mice in a cage with a RW will preserve OD-plasticity in old animals after a cortical lesion in S1, as well as the therapeutic effect of running after stroke on OD-plasticity. Our data suggest that physical exercise not only preserved but also restored OD-plasticity after a localized cortical stroke. Additionally, we tested how long the positive effect of EE on OD-plasticity lasts, when mice are transferred to a less stimulating environment. For this purpose mice raised in EE until PD130 were moved to normal SCs and after a short period MD was performed. We found that already after 1 week in a SC, mice did not show OD-plasticity. We tried a pharmacological approach to restore OD-plasticity in those mice by administrating fluoxetine (selective serotonin reuptake inhibitor). However, treatment with fluoxetine did not preserve OD-plasticity. On the other hand, when mice were transferred from EE to a SC with RW, OD-plasticity was preserved. Furthermore, we investigated the posibility of the effect of EE on OD-plasticity to be transferred to the next generation. To this end, after mating of EE-mice, pregnant dams were transferred to SCs few days before delivery. Offspring was raised exclusively in SCs up to at least PD120. We found, that offspring of EE-parents showed an OD-shift similar to EE-mice while age matched SC-mice did not. Additionally, we tested which parent is responsible for the transmitted effect of EE. For this purpose EE-females were mated with SC-males, or EE-males with SC-females, respectively. Only offspring of EE-mother and SC-father showed an OD-shift after MD. To summarize, the adult offspring of enriched parents still displayed a juvenile OD-plasticity in V1, even if they did not experience any EE and most likely the responsible parent is the mother.