FBN
Federico Massa, could you take us through the steps that led to this publication in PNAS ?

Federico Massa
Adult neurogenesis is a process by which our brain produces new neurons once fetal and early postnatal development has ceased. The dentate gyrus (DG) of the hippocampus is one of the few subregions of the brain where thousands of newborn cells are generated daily. Although these adult-born neurons are involved in hippocampal functions, their specific contribution to synaptic plasticity remains largely unknown.

Whereas this issue can be addressed through the inhibition of adult neurogenesis, the different experimental approaches used so far to prevent newborn neuron generation, such as pharmacological or irradiation-mediated procedures, lacked specificity and had unwanted side effects.

To unravel the contribution of adult neurogenesis, we took advantage of a recently developed inducible transgenic mouse that allows the specific ablation of adult–born neuron. Developed in the groups of Nora Abrous and Pier-Vincenzo Piazza, this model is based on double transgenic mice, in which new-born neurons can be selectively killed through the over-expression of an apoptotic protein.


"Like with a switch, we are able to turn off adult neurogenesis and examine its impact on brain functions and, most importantly, we can afterward restore it, with the great advantage of studying the integration of new neurons in the DG network in a time dependent manner."
Using an electrophysiological approach, we demonstrated that selective ablation of adult-born neurons has a strong impact on hippocampal synaptic transmission.

Furthermore, long-term potentation (LTP) and long-term depression (LTD), considered one of the major cellular mechanisms that underlies learning and memory, are largely compromised at DG synapses. Interestingly, the deficits in synaptic transmission and plasticity are completely rescued by restoring neurogenesis and these synapses regain their ability to express LTP much faster than their ability to express LTD.

FBN
So in the end, what have you demonstrated ?

Federico Massa
We demonstrated that adult hippocampal neurogenesis is a key process influencing the plastic properties of the DG by facilitating the expression of LTP and LTD in a sequential time dependent manner as newborn neurons are incorporated into the hippocampal network. This structural and functional plasticity may represent an important contributor to the ability to form new memories.