My research focuses on the functional relevance of adult neurogenesis in the mammalian dentate gyrus. My data indicate that young neurons contribute significantly to memory and hippocampal plasticity and suggests that their reduction during conditions such as stress, depression, radiotherapy and ageing may be a causative factor underlying learning and memory impairments.

My graduate work showed that new neurons have a lower threshold for inducing long-term potentiation (LTP), a synaptic model of memory, than mature neurons. Antagonists for the NR2B type NMDA receptor selectively blocked young neuron LTP indicating that this "juvenile" form of the NMDA receptor may endow young neurons with their enhanced plasticity. I also found that young neurons could potentiate with intact GABAergic inhibition whereas mature neurons required pharmacological disinhibition to potentiate. Finally, young neuronal LTP was stable whereas mature neuronal LTP decayed continuously following induction. I subsequently decided to investigate the contribution of young neurons to learning in the spatial water maze task. Using irradiation to kill the dividing precursor population we found that neurogenesis is not required to learn this task. However, while irradiated rats had intact memory 1 week after training, memory was completely abolished at 2 and 4 weeks post-training.

As a postdoc I have examined activity-dependent gene expression in young neurons during different phases of learning. Zif268 is a transcription factor immediate-early gene which is required for long-term plasticity and memory and is upregulated in neurons involved in memory formation. By combining immunohistochemistry for young neurons with learning-induced zif268 expression I have found that young neurons are actually inhibited during acquisition of a water maze task. Instead, young neurons had enhanced activation during the retrieval of 1w old memories. Thus, by reducing neurogenesis and by monitoring young neuron activity it appears that young neurons are less important for initially acquiring spatial memories and more involved in processing long-term memories.