Hippocampal plasticity: Development of connectivity and growth hormone modulation of place cells and behavior

Abstract

The hippocampus is remarkably plastic and has the ability to modify its processes throughput the lifetime. During development, the hippocampus is exceedingly plastic as new neurons and connections are taking form. Nevertheless, the neural circuits of the hippocampus keep modifying in the adult. The factors contributing to hippocampal plasticity are still elusive. In this thesis, I present three papers in which I investigate different aspect of plasticity in the hippocampus using Long Evans rats. In the first paper using anatomical tracing approach, I showed that the first postnatal projections from the hippocampus and parahippocampus to the retrosplenial cortex are present at birth and display adult-like topography. These results indicate that the projections are independent on environmental factors. In the second and third papers, using adeno-associated viruses to overexpress the neuromodulator growth hormone (GH) or the antagonizing GH (aGH). In the second paper using behavioral tasks, I showed that GH enhanced hippocampal memory in a spontaneous recognition task, enhanced spine density. The aGH impaired memory performance in the Morris water maze task and decreased the spine density. In the third paper using single-unit recording, I found that GH tended to induce global remapping while aGH impaired remapping events. The results from the last to papers suggest that GH modulates hippocampal memory in which it reduces the interference of similar memories. Taken together, different factors contribute to changes in the hippocampus, and revealing such factors can have great importance for understanding the mechanisms behind memory deficiency as well as normal development and ageing.