Periodic Reporting for period 1 - CaRe-Space (Cajal-Retzius cells role in the development of the spatial navigation system)
Periodo di rendicontazione: 2020-01-01 al 2021-12-31
Cajal-Retzius (CR) cells were discovered at the end of the 19th century by one of the founding fathers of Neuroscience - Ramon y Cajal. Hundred years have passed and yet, we still know very little about these neurons. CR cells are crucial during prenatal development for the correct formation of the cortex. Most CR cells die soon after birth. However, there is one specific part of the brain, the hippocampus, a region important for learning and memory, where these cells survive for a long time.
The role that CR cells play in hippocampus-dependent memories is still unknown. The hippocampal-parahippocampal region forms a network responsible for spatial representation in rodents and humans. In both species, spatial navigation shows a delayed postnatal maturation, which correlates with the persistence of CR cells. CR cells are indeed located in a key position to control the development of the entorhinal-hippocampal connections. It has been previously shown that CR cells are an active part of the hippocampal circuit. The CaRe-Space project aimed to establish the role that CR cells play in the postnatal hippocampus and their contribution to the development of spatial mapping. To reach this goal, I used specific genetic and molecular tools, to ablate hippocampal CR cells at early postnatal stages. I then analyzed alterations of both the circuit of the hippocampal region and the spatial navigation system. Results collected through CaRe-Space show that the persistence of CR cells is critical for the proper maturation of the hippocampal circuit.
The last decade has seen a major global effort in trying to understand how the brain processes information. Indeed, several research groups are investigating how spatial maps are created in the brain. However, few studies have focused on how the involved circuits actually develop and what the consequences of an improper maturation are. The CaRe-Space project results are giving us a new understanding on the role that specific type of neurons play in the development of the circuits supporting learning and memory. This knowledge is fundamental to fully grasp the phenotype of neurodevelopmental disorders in which the hippocampal region is affected. Additionally, it paves the way for studies focusing on the role of CR cells in such disorders.
The role that CR cells play in hippocampus-dependent memories is still unknown. The hippocampal-parahippocampal region forms a network responsible for spatial representation in rodents and humans. In both species, spatial navigation shows a delayed postnatal maturation, which correlates with the persistence of CR cells. CR cells are indeed located in a key position to control the development of the entorhinal-hippocampal connections. It has been previously shown that CR cells are an active part of the hippocampal circuit. The CaRe-Space project aimed to establish the role that CR cells play in the postnatal hippocampus and their contribution to the development of spatial mapping. To reach this goal, I used specific genetic and molecular tools, to ablate hippocampal CR cells at early postnatal stages. I then analyzed alterations of both the circuit of the hippocampal region and the spatial navigation system. Results collected through CaRe-Space show that the persistence of CR cells is critical for the proper maturation of the hippocampal circuit.
The last decade has seen a major global effort in trying to understand how the brain processes information. Indeed, several research groups are investigating how spatial maps are created in the brain. However, few studies have focused on how the involved circuits actually develop and what the consequences of an improper maturation are. The CaRe-Space project results are giving us a new understanding on the role that specific type of neurons play in the development of the circuits supporting learning and memory. This knowledge is fundamental to fully grasp the phenotype of neurodevelopmental disorders in which the hippocampal region is affected. Additionally, it paves the way for studies focusing on the role of CR cells in such disorders.
In CaRe-Space, I combined the use of viral vectors and transgenic mice, with in vitro electrophysiology, immunohistochemistry and in vivo recordings from freely moving animals. I developed a new approach to study the role of CR cells in the postnatal hippocampus by ablating these cells at early stages of postnatal development. I then performed an analysis of the hippocampal circuits to study how the inputs from the entorhinal cortex to CA1 pyramidal cells are affected by such ablation. I also reconstructed the cell-morphology to investigate how dendritic spines change in this condition. Finally, I performed in vivo recordings from freely moving mice to determine if the maturation of hippocampal place cells required the presence of CR cells. The data collected show that, indeed, the persistence of CR cells in the postnatal hippocampus is essential for the circuits of the hippocampal region to correctly mature.
I presented the results from the CaRe-Space project at several scientific conferences (Federation of European Neuroscience Societies Forum 2020), webinars (e.g. Cells Webinar “Nervous system development and plasticity”, a seminar series hosted by Dr. Sepand Rastegar, Institute of Biological and Chemical Systems, Karlsruhe Institute of Technology, Germany) and online symposia (e.g. Symposium honoring Prof. Jacopo Magistretti, University of Pavia, Italy; US-Nordic Precision Neuroscience speed networking event, hosted by Virginia Tech), and at invited departmental talks. I will also deliver further presentations at several scientific conferences in 2022. More information on the results is available at https://quattrocololab.com. I will also publish an Open Access manuscript including the project’s main finding in 2022 which I will make available as pre-print on bioRxiv.
I presented the results from the CaRe-Space project at several scientific conferences (Federation of European Neuroscience Societies Forum 2020), webinars (e.g. Cells Webinar “Nervous system development and plasticity”, a seminar series hosted by Dr. Sepand Rastegar, Institute of Biological and Chemical Systems, Karlsruhe Institute of Technology, Germany) and online symposia (e.g. Symposium honoring Prof. Jacopo Magistretti, University of Pavia, Italy; US-Nordic Precision Neuroscience speed networking event, hosted by Virginia Tech), and at invited departmental talks. I will also deliver further presentations at several scientific conferences in 2022. More information on the results is available at https://quattrocololab.com. I will also publish an Open Access manuscript including the project’s main finding in 2022 which I will make available as pre-print on bioRxiv.
The role that CR cells play in the postnatal hippocampus has long been overlooked, even if evidence showed these neurons are an active component of the hippocampal circuits. The results collected through CaRe-Space show that the persistence of these cells is essential for the correct development of the circuit of the hippocampal region. This knowledge represents a major step-forward for the study of circuits supporting fundamental cognitive abilities such as learning and memory. In addition, the project’s results have the potential to increase our understanding of the pathophysiology of specific neurodevelopmental disorders in which memory is impaired (e.g. autism, Down Syndrome, Williams-Beuren Syndrome).