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Microcircuit functioning investigated with high-density multielectrode arrays and two-photon calcium imaging ex vivo, to address network dynamics and plasticity

 

 

 

Neuronal networks are responsible for complex processing of incoming information and account for the main functions of an entire brain region. The cerebellar cortex, for example, is characterized by a well-organized circuit that can be explored in each component ex vivo using cutting edge techniques as 3D high-density MEAs and 2-photon calcium imaging. This allows us to reconstruct the spread of activity in complex circuits, from the input to the output layer.

 

Some of the complex properties of neuronal networks that can be explored using these techniques are:

– the spatial distribution of excitation and inhibition (the so-called “excitatory/inhibitory ratio” – E/I);

– the impact of single connection dynamics on the network processing, due to different short-term plasticity properties and their distribution along the circuit;

– the development of long-term plasticity at the network level, the spatial distribution of long-term potentiation (LTP) and long-term depression (LTD) and the consequences on network functioning;

– the alteration of network functioning in mouse model of neurodevelopmental and neurological disorders (see the dedicated page).

 

A PhD student involved in this research topic will have the opportunity to characterize neuronal networks activity in physiological and/or pathological conditions, learning to master these state-of-the-art techniques. The laboratory has a consolidated expertise in cerebellar physiology, while more research lines involve the cerebral cortex (prefrontal and somatosensory cortex).

 

 

References

Monteverdi A, Di Domenico D, D’Angelo E, Mapelli L. Anisotropy and Frequency Dependence of Signal Propagation in the Cerebellar Circuit Revealed by High-Density Multielectrode Array Recordings. Biomedicines. 2023 May 18;11(5):1475. doi: 10.3390/biomedicines11051475. PMID: 37239146; PMCID: PMC10216013.

Gagliano G, Monteverdi A, Casali S, Laforenza U, Gandini Wheeler-Kingshott CAM, D’Angelo E, Mapelli L. Non-Linear Frequency Dependence of Neurovascular Coupling in the Cerebellar Cortex Implies Vasodilation-Vasoconstriction Competition. Cells. 2022 Mar 19;11(6):1047. doi: 10.3390/cells11061047. PMID: 35326498; PMCID: PMC8947624.

Mapelli L, Dubochet O, Tedesco M, Sciacca G, Ottaviani A, Monteverdi A, Battaglia C, Tritto S, Cardot F, Surbled P, Schildknecht J, Gandolfo M, Imfeld M, Cervetto C, Marcoli M, D’Angelo EMaccione A. Design, implementation, and functional validation of a new generation of microneedle 3D high-density CMOS multi-electrode array for brain tissue and spheroidsbioRxiv 2022.08.11.503595; doi: https://doi.org/10.1101/2022.08.11.503595

Casali S, Tognolina M, Gandolfi D, Mapelli J, D’Angelo E. Cellular-resolution mapping uncovers spatial adaptive filtering at the rat cerebellum input stage. Commun Biol. 2020 Oct 30;3(1):635. doi: 10.1038/s42003-020-01360-y. PMID: 33128000; PMCID: PMC7599228.