Neuronal plasticity

Alejandro F. Schinder - Fundación Instituto Leloir


Neuronal Plasticity

Our lab investigates mechanisms of plasticity of the adult mammalian brain. In particular we are interested in adult hippocampal neurogenesis. The dentate gyrus of the hippocampus contains neural stem cells that generate neurons through life. We focus on two central aspects of this process:
  • The factors that modulate development and functional integration of newborn neurons in the preexisting circuits;
  • How the dentate gyrus input/output relationship is continuously reshaped as a consequence of adult neurogenesis.
The adult hippocampus contains self-renewing neural stem cells (NSCs) that generate neurons throughout life. Whether adult neurogenesis is relevant for brain function is a matter of intense experimentation and debate. 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 understand how adult-born GCs connect within the existing hippocampal network. We used fluorescent reporters to compare GCs born during development and adulthood and found that, when fully mature, GCs born at all stages converge into a homogeneous population with indistinguishable connectivity and functional properties. We used optogenetics to describe their output and demonstrated that adult-born GCs make synaptic contacts onto several types of target cells in the hippocampus. 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 found that one of the most important features seems to be what new GCs might do while they are immature developing cells. Our recent findings have indicated that immature GCs are highly sensitive to weak afferent activity and integrate a broad variety of synaptic inputs from different origin when compared to mature neurons, which are highly input-specific. Interestingly, these unique processing capabilities remain during a critical period that ends as neurons leave the immature stages. We concluded that adult neurogenesis then serves to maintain renewable cohorts of highly integrative GCs in the dentate gyrus. We are now digging into the mechanisms underlying these network properties conferred by immature GCs and designing novel approaches to determining their behavioral implications.

Toni, N., Laplagne, D.A., Zhao, C., Lombardi, G., Ribak, C.E., Gage, F.H., Schinder, A.F. Neurons born in the adult dentate gyrus form functional synapses with target cells. Nat Neurosci. 11: 901-907 (2008).     PubMed

Laplagne, D.A., Espósito, M.S., Piatti, V.C., Morgenstern, N.A., Zhao, C., van Praag, H., Gage, F.H., Schinder, A.F. Functional Convergence of Neurons Generated in the Developing and Adult Hippocampus. PLoS Biol. 4: e409 (2006).     PubMed

Espósito, M.S., Piatti, V.C., Laplagne, D.A., Morgenstern, N.A., Ferrari, C.C., Pitossi, F.J., Schinder, A.F. Neuronal differentiation in the adult hippocampus recapitulates embryonic development. J Neurosci. 25: 10074-10086 (2005).     PubMed

Van Praag, H., Schinder, A.F., Christie, B.R., Palmer, T.D., Gage, F.H. Functional neurogenesis in the adult hippocampus. Nature. 415: 1030-1034 (2002).    PubMed

Alejandro F. Schinder
Head or Laboratory -

Damiana Giacomini
Assistant Investigator CONICET

Verónica Piatti
Assistant Investigator CONICET

Mariela Trinchero
Postdoctoral Fellow CONICET

Ayelén Groisman
Doctoral Fellow

Paula González Giqueaux
Doctoral Fellow

Natalí Rasetto
Doctoral Fellow

María Cristina Monzón
Laboratory technician

Magalí Herrero
Master Student

Natalia Soldi
Master Student