Nilsbo · Investigating the role of adult neurogenesis in spatial memory through optogenetic monitoring of neural activity

The idea that neurogenesis in the mammalian brain only takes place during development has been abandoned. One of the two regions where neurogenesis takes place in the adult mammalian brain is the sub-granular zone in the dentate gyrus. Although accumulating evidence suggests that newborn neurons in the adult dentate gyrus have a role in learning and memory, current methods using ablation and IEG mapping techniques have not been able to reveal what stimuli new neurons are activated by or what kind of information new neurons’s spiking activity encodes during behaviour, because of controversial results in ablation studies and poor temporal resolution of IEG mapping. In this project, we aim to develop a novel technical approach overcoming this limitation and to determine dynamic neuronal activity of new neurons at temporal resolution of single spikes. We combine multiple single-unit in vivo recording with optogenetics to identify and subsequently measure the activity of adult newborn neurons in the dentate gyrus during behaviour. The Channelrhodopsin gene encoding a light-sensitive cation channel will be delivered into newborn neurons using viral vectors. In this way, we are able to tag the newborn neurons so that they respond to light stimulation by generating action potentials. Light-induced action potentials will be used to identify activity of targeted neurons in behaving animals. Using this method we will be the first to record the natural activity of newborn neurons in the hippocampus. Based on the previous findings suggesting the involvement of new neurons in spatial memory formation, we hypothesize that new neurons are involved in spatial information processing by exhibiting place-cell activity, which fires action potentials corresponding to specific animal’s locations. In order to test this hypothesis, we will examine activity of newborn neurons during spatial exploration. This way we can directly test their hypothesized involvement in learning and memory.