Microcircuit remodeling processes underlying learning in the adult

Donato, Flavio. Microcircuit remodeling processes underlying learning in the adult. 2013, Doctoral Thesis, University of Basel, Faculty of Science.


Official URL: http://edoc.unibas.ch/diss/DissB_10613

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One of the most intriguing discoveries in neuroscience of the past decades has been showing that experience is able to induce structural modifications in cortical microcircuit that might underlie the formation of memories upon learning (for a review, see Caroni, Donato and Muller 2012). Hence, learning induces phases of synapse formation and elimination that are strictly regulated by a variety of mechanisms, which impact on cortical microcircuits affecting both excitatory and inhibitory neurons. Nevertheless, the extent to which specific configurations might be implemented to support specific phases of learning, as well as the impact of experience-induced structural modifications on further learning, is still largely unknown.
Here, I explore how the remodeling of identified microcircuits in the mouse hippocampus and neocortex supports learning in the adult.
In the first part, I identifiy a microcircuit module engaging VIP and Parvalbumin (PV) positive interneurons to regulate the state of the PV+ network upon experience. This defines states of enhanced or reduced structural plasticity and learning based on the distribution of PV intensity in the network.
In the second part, I demonstrate how specific hippocampal subdivisions are exploited to learn subtasks of trial-and-errors forms of learning via the deployment of increasingly precise searching strategies, and sequential recruitment of ventral, intermediate, and dorsal hippocampus.
In the third part, I highlight the existence of genetically matched subpopulations of principal cells in the hippocampus, which achieve selective connectivity across hippocampal subdivisions via matched windows of neurogenesis and synaptogenesis during development.
In the fourth part, I investigate the maturation of microcircuits mediating feedforward inhibition in the hippocampus, and highlight windows during development for the establishment of the proper baseline configuration in the adult. Moreover, I identify a critical window for cognitive enhancement during hippocampal development.
In the fifth part, I study how ageing affects the PV network in hippocampal CA3, providing evidence for which age related neuronal loss correlates to reduced incidental learning performances in old mice. Therefore, by manipulating the PV network early during life, I provide strategies to modulate cognitive decline.
Advisors:Caroni, Pico
Committee Members:Arber, Silvia
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Neurobiology > Cell Biology (Arber)
UniBasel Contributors:Arber, Silvia
Item Type:Thesis
Thesis Subtype:Doctoral Thesis
Thesis no:10613
Thesis status:Complete
Number of Pages:261 S.
Identification Number:
edoc DOI:
Last Modified:22 Jan 2018 15:51
Deposited On:09 Dec 2013 16:09

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