Development of entorhinal connectivity-continuation
This application is a continuation of application #5049 with the same name. The research proposed in that application has been very successful, but slower than anticipated. We only carried out part of the proposed experiments, which is reflected in the number of reported animals compared to the originally requested number of animals. In this continuation, we aim to address some of the remaining questions originally proposed.
The entorhinal cortex is a key element in the larger cortico-hippocampal system which is crucially involved in learning and memory. There is convincing evidence that this network is functionally organized as two parallel networks, mediated by the medial and lateral subdivisions of the entorhinal cortex respectively. The network mediated by the medial entorhinal cortex is strongly implicated in spatial navigation by providing a stable code of where the animal is in space through the well-known grid cells. Over the years many additional cell-types relevant for navigation have been described in various components of the network. The lateral entorhinal cortex, in contrast contains neurons that seem to specifically code for sensory stimuli that are present in the environment, such as certain objects and their position in space. This is embedded in a network that overall codes for object and context detection and novelty. In this project, we aimed to explore whether these specific functional differences between neurons in the two entorhinal subdivisions are set up during postnatal development.
The overarching research goals are fundamental, contributing to our quest to describe how the brain develops the higher order capacities such as navigational and recognition skills. All our findings form the foundation to investigate why the entorhinal cortex is among the first brain regions which express symptoms for Alzheimer’s disease. Over the recent years, we published a number of papers illustrating this productive transfer from basic to applied science. In the current continuation, we aim to finalize our experimental observations obtained thus far on the development of cortical inputs to the medial entorhinal cortex.
We will carry out experiments on 250 rats of either sex and different ages from newborn to postnatal day 30. Animals will undergo a single surgery under appropriate levels of anaesthesia, during which either chemical or biological marker substances will be injected into the brain. The animals recover well from the surgery and are accepted back by the mother to receive continued parental care. After a period of 1 – 10 days, the animals will be euthanized and used for connectivity analysis,by obtaining brain slices, which can be maintained for a number of hours to do electrophysiological experiments. The overall burden to the animals is considered to be moderate lasting for up to two, max 3 days at most following surgery.
The entorhinal cortex is a key element in the larger cortico-hippocampal system which is crucially involved in learning and memory. There is convincing evidence that this network is functionally organized as two parallel networks, mediated by the medial and lateral subdivisions of the entorhinal cortex respectively. The network mediated by the medial entorhinal cortex is strongly implicated in spatial navigation by providing a stable code of where the animal is in space through the well-known grid cells. Over the years many additional cell-types relevant for navigation have been described in various components of the network. The lateral entorhinal cortex, in contrast contains neurons that seem to specifically code for sensory stimuli that are present in the environment, such as certain objects and their position in space. This is embedded in a network that overall codes for object and context detection and novelty. In this project, we aimed to explore whether these specific functional differences between neurons in the two entorhinal subdivisions are set up during postnatal development.
The overarching research goals are fundamental, contributing to our quest to describe how the brain develops the higher order capacities such as navigational and recognition skills. All our findings form the foundation to investigate why the entorhinal cortex is among the first brain regions which express symptoms for Alzheimer’s disease. Over the recent years, we published a number of papers illustrating this productive transfer from basic to applied science. In the current continuation, we aim to finalize our experimental observations obtained thus far on the development of cortical inputs to the medial entorhinal cortex.
We will carry out experiments on 250 rats of either sex and different ages from newborn to postnatal day 30. Animals will undergo a single surgery under appropriate levels of anaesthesia, during which either chemical or biological marker substances will be injected into the brain. The animals recover well from the surgery and are accepted back by the mother to receive continued parental care. After a period of 1 – 10 days, the animals will be euthanized and used for connectivity analysis,by obtaining brain slices, which can be maintained for a number of hours to do electrophysiological experiments. The overall burden to the animals is considered to be moderate lasting for up to two, max 3 days at most following surgery.