The importance of neuroplasticity and excitability of adult-born neurons in alleviating depression and anxiety-like behaviour in mice

Abstract

The increase in excitability of newborn adult neurons had been shown to have an antidepressant effect in rodents in previous studies, however whether the same result would apply to mature neurons remains unknown. This paper therefore proposes two experiments that investigate the role of neuroplasticity and mature neuron excitability in reducing depressive behaviour in rodents. Old neurons are known to have reduced neuroplasticity compared to newborn neurons, and the main factor influencing this seems to be the reduced NMDA:AMPA receptor ratio in mature neurons. By knocking out the NR1 gene that codes for the NMDA receptor in newborn neurons, experiment one investigates whether reduced neuroplasticity in the rodent hippocampus would induce anxiety-like behaviour, thus the importance of adult hippocampal neurogenesis (AHN) in maintaining neuroplasticity in the brain and normal affective behaviour. Subsequently the artificially made-mature neurons in the hM4Dq+ tamoxifen inducible Cre-recombinase transgenic mouse line are being activated through injection of tamoxifen followed by CNO, which increases neuronal excitability. This is hypothesised to reduce depressive behaviour to an extent however less effective than activating newborn neurons. These experiments can potentially be valuable in the application of relevant depression treatments in humans, alongside with the maintenance and stimulation of AHN with regards to its anti-depressive effect