Forsøksdyr: Development of the circuits of the hippocampal region

Godkjenningsdato 23.10.2020

Godkjenningsperiode 01.01.2021-31.12.2024

The hippocampal formation plays a major role in the formation and retrieval of memories. It creates spatial maps that animals use to navigate the environment. The circuits for these features are refined around birth and during the first weeks of postnatal development. In these first postnatal weeks, the hippocampus undergoes a developmental critical period, in which its functional maturation is experience-dependent. Defining the development of the hippocampal circuitry during this critical period of maturation is fundamental to understand the network function in both normal development and in neurodevelopmental disorders.
Transient population of cells or circuits are present during the first weeks of postnatal development and have a critical role for the correct formation and maturation of circuits. For example, the postnatal hippocampus is characterized by Cajal-Retzius cells, a transient population of cells whose role is still unknown.
The overall scientific aim of this project is to understand the influence of specific cell types on the network of the hippocampal formation and what role they play in its maturation and function. Multiple techniques, from anatomical tracing to transcriptomic, from in vitro to in vivo physiology, will be used to achieve this goal. In addition, we will use a combination of transgenic mice and viral vectors to achieve specific manipulation of cells at different developmental stages and study how this affects the maturation of the hippocampus and of the spatial memory system.
We aim to use a total of 1584 transgenic mice of either sex. To ensure the wellbeing of the mice, we will use enriched environment and small group housing, whenever possible. Surgical procedures will be performed to i) inject viral vectors to label or manipulate cells, for anatomical, molecular or in vitro electrophysiological studies, or ii) to implant ultrathin electrodes for recording electrical activity in different areas of the hippocampal region. The procedures are continuously monitored and validated by the animal caretakers and the local veterinarian, and they are evaluated as moderate, since the animals are completely recovered after 2 days. All the personnel involved is trained and licensed to perform animal experiments and will take part in regular training updates. We aim to reduce the number of animals used to the minimum required to achieve statistical power or, concerning descriptive studies, to what is conventionally accepted by the scientific community. All the techniques are well established in the lab or in the department, and procedures have been refined to ensure the best possible recovery and well-being of the animals. Study of neuronal connectivity and circuit function cannot currently be performed without the use of animals.