Network activity in the rodent entorhinal cortex. (360G-Wellcome-077703_Z_05_A)

1.    Network activity in the rodent entorhinal cortex The entorhinal cortex (EC) and hippocampus are closely interconnected structures involved in spatial navigation and memory. The superficial layers of the EC provide the main cortical input to the hippocampus, whereas the deep layers of the EC receive the main cortical output from the hippocampus. We aim to investigate the temporal relation between the cortical input to and output from the hippocampus, by recording multiunit activity simultaneously in the superficial and deep layers of the EC. In particular, we will record activity during sleep and test whether activity in the EC is altered by waking experience in either of two simple contrasting environments. It has been reported that hippocampal neuronal activity during wakefulness is replayed during subsequent sleep. We would compare spike patterns recorded in the EC during active exploration with those replayed during sleep immediately following exposure to each of the two environments. Our prediction is that replay would be seen in deep layer neurons of the EC, the major target of the CA1 hippocampal cells, but not in the superficial layers. The results will have implications for our understanding of neuronal activity involved in spatial navigation and memory. In order to investigate these aims we have a number of particular objectives: To describe the firing relations of deep and superficial layer EC neurones during slow-wave oscillations (i.e. during UP and DOWN states) under anaesthesia. To characterise the same relations during natural sleep, and compare this to the anaesthesia data. To record in vivo EC firing relationships during behaviour, and examine whether recorded patterns are replayed during subsequent sleep periods. To observe sleep-like activity (UP and DOWN states) in hippocampal/entorhinal slices using patch clamp recording from both deep and superficial layers - to confirm an electrophysiological model. To observe UP/DOWN state activity across EC layers using calcium imaging combined with patch recordings - to demonstrate an imaging model. To observe the spatial distribution of EC neuronal recruitment during UP/DOWN states (e.g. sequential recruitment of different layers) and resultant effects on signal propagation from the hippocampus.