Animal model: mouse.
Methods: transgenic mice, AAV injections, in-vivo imaging, computational model.
Intro: Adult neurogenesis is one of the most mysterious features of the adult brain. In this paper the Authors explore how adult-generated granule cells (abGCs) affect mitral cells (MCs) responses, using both in-vivo imaging experiments and computational models.
Main findings: First, the Authors identify a new model to target more effectively abGCs, the Nestin-cre ERT2 driver crossed with the reporter tTA2 and histone –BFP. In this model, the number of abGCs is two times higher than the more commonly used Nestin-cre ERT2 mouse.
Second, contrary to the common model, the Authors show that silencing young adGCs induce the suppression of odor-evoked responses in MCs (in awake animals they observe a reduction of excited and suppressed responses), and broadening MCs tuning. This effect is only transient, probably due to the higher excitability of young abGCs. On a population level, this effect on abGCs improves odor discrimination by MCs. Third, the Authors model the activity of MC, abGCs, and GCs to investigate: 1) how the reduction of excited and suppressed responses can arise from the same neuron cohort; 2) how a small fraction (2.5% of the whole GCs are abGCs) of cells can have such a strong impact on the circuit. AbGCs higher excitability and higher input promiscuity is the key to the increase MC discriminability by augmenting MC dynamic range.
Conclusion: I find the paper overall interesting, especially for those who are interested in adult neurogenesis. The mouse model seems a robust tool for further investigations, but in some of the experiments, it has been subject to too many manipulations (AAV injections, virus injection…) which might make it difficult to replicate in other labs. Interesting are the results, especially the counter-intuitive effect of abGCs silencing. However, I really appreciated the effort in trying to simulate MC-GCs circuit and adding abGCs.
Further questions: in this paper the author explored the effect of abGCs on MC, what about TC? Some of the computation performed by abGCs (but also more generally speaking by GCs) seems to be performed by the network. In my opinion, the description of abGCs connectivity will be key to understand mechanistically the role of adult neurogenesis.