The adult brain contains self-renewing neural stem cells (NSCs) that generate neurons throughout life. In mammals, adult neurogenesis is restricted to the so-called neurogenic niches, the olfactory bulb, and the dentate gyrus of the hippocampus—a cortical structure involved in learning and memory. Whether adult neurogenesis is relevant for brain function is a matter of intense experimentation and debate. Increasing evidence supports the notion that adult neurogenesis is modulated by brain function and is involved in information processing in specific circuits. My lab is interested in the plastic modifications of adult hippocampal networks produced by the incorporation of newly generated dentate granule cells (GCs).
The impact of adult-born GCs on hippocampal function is primarily determined by their number, connectivity, synaptic properties, and excitability. In recent years, we have combined retroviral labeling with optogenetics to help us understand how adult-born GCs connect within the existing hippocampal network (i.e., identifying afferents and targets as well as their synaptic weights and spatial distribution). We used different fluorescent reporters to compare GCs born in the embryonic, postnatal, and adult hippocampus and revealed that, when fully mature (after 6–8 weeks), GCs born at all developmental stages converge into a homogeneous population with indistinguishable afferent connectivity with regard to both glutamate and GABA, the main excitatory and inhibitory neurotransmitters. They also display similar firing properties. We also used Channelrhodopsin 2 to describe their output and demonstrated that adult-born GCs make synaptic contacts onto hilar interneurons, mossy cells, and CA3 pyramidal cells and release glutamate as their main neurotransmitter, typical features of all development-generated GCs.
During all of these years we continued to bear two simple questions in mind: Why does the adult hippocampus continue to generate neurons? What is special about adult-born neurons? We then turned to the hypothesis that what is important is not what new GCs do when they are mature but what they might do while they are immature developing cells. Indeed, our recent findings have indicated that immature GCs (four weeks old) are highly sensitive to weak afferent activity and integrate a broader variety of synaptic inputs from different origin than do mature neurons, which are highly input specific. Interestingly, these unique processing capabilities remain during a critical period that ends when neurons are eight weeks old. In this context, immature neurons represent a population of integrators that are broadly tuned during a transient period and may encode most features of the incoming afferent information. While developing, new GCs display a high activation threshold and input specificity and will, therefore, become good pattern separators. Adult neurogenesis would then maintain the renewable cohorts of highly integrative GCs in the dentate gyrus. Finally, the unique functional properties described here support a hypothesis whereby activity reaching the dentate gyrus undergoes differential decoding through immature neuronal cohorts that are highly responsive and integrative and, in parallel, through a large population of mature GCs with sparse activity and high input specificity. We are digging into the mechanisms underlying these network properties conferred by immature GCs and designing novel approaches to determining their behavioral implications.
As of September 26, 2012