Simona Lodato Principal Investigator View More
- AddressVia Rita Levi Montalcini 4, Building E, 20090 Pieve Emanuele
- Telephone+39 0282245119
Our research is focused on understanding the cellular and molecular events that govern the development of the mammalian brain. In particular, we are interested in deciphering the genetic and environmental mechanisms that control the coordinated assembly of stereotyped and sophisticated neuronal circuits in the cerebral cortex, the region of our brain that has undergone the most pronounced expansion during evolution. Indeed, complex brain functions and critical behaviors such as movement planning and control as well as emotion processing and cognition are executed by highly sophisticated and stereotyped neural networks, which are composed by an outstanding array of distinct excitatory projection neuron (PN) and inhibitory interneuron (IN) subtypes that populate the cerebral cortex. In our lab, we aim at decoding the molecular strategies by which different types of PNs and INs properly acquire their distinct molecular and functional identity and coordinate their migratory behaviors to eventually assemble into distinct balanced microcircuits. Alterations in the excitatory/inhibitory balance during cortical development are often associated with numerous neuropsychiatric and neurodevelopmental disorders, like schizophrenia, epilepsy and autism spectrum disorders. Our aim is to investigate the cellular and molecular substrates, as well as the susceptible developmental time window, affected in the distinct neurodevelopmental and adolescent disorders, with the ultimate goal of identify early biomarkers and therapeutic strategies.
In order to investigate the molecular and cellular events that govern the establishment and maintenance of specific cortical microcircuits during embryonic and postnatal development, in our lab we employ a variety of experimental approaches, including viral strategies for circuit tracing and functional manipulation, isolation and molecular characterization of genetically and functionally distinct PN and IN types – via single-cell genomics –, and in vivo gene editing, in both physiological and pathological conditions. We also combine multi-parametric flow cytometry (FACS) to isolate both cells and nuclei, and advanced RNA sequencing approaches to dissect at the single cell level the mechanisms underlying the assembly of cortical circuits.
Deciphering the molecular code underlying the interaction between distinct classes of projection neurons and interneurons in the developing cortex
Upon isolation and molecular dissection of distinct classes of PNs and INs across multiple developmental time points, we will dissect both in vitro and in vivo the “pairing” mechanisms utilized by the distinct partners to coordinate their migration, and select distinct synaptic targets. We are working at the identification of molecules and signaling pathways that mediate the specific interactions. We are also interested in investigating the impact of these specific interactions on the development and assembly of the other non-neuronal cells types that populate the cortex.
Investigating the cellular and molecular substrate of Autism Spectrum Disorder and Intellectual Disabilities
By combining molecular, genetic, biochemical and immunocytochemical methods, with high-resolution, live-cell imaging of neurons (including super-resolution microscopy, STED) and in vivo transplantation of IPCS-derived neurons, we plan on highlight the cellular substrate and the molecular patterns of selective vulnerability in neurodevelopmental and neuropsychiatric disorders, including Autism Spectrum Disorders, Intellectual Disabilities and Schizophrenia.
Simona Lodato Publications
Selected Publications: 20-25 publications listed in details with all the contributing authors, title of the papers, journal, dates. Mancinelli S and Lodato S Dissecting neuronal diversity and temporal dynamics in ...