Revealing the cellular and synaptic mechanisms underlying the diverse firing properties of hippocampal pyramidal cells during behavior.
In vivo two-photon [Ca2+] imaging are performed in head-restrained mice while performing navigation in virtual reality to functionally characterize distinct pyramidal cells. This is followed by post hoc in vitro electrophysiological and anatomical experiments to reveal differences in intrinsic properties and synaptic innervation of the functionally characterized nerve cells.
Understanding the function of the hippocampal formation has been in the focus of system neuroscience for many decades, revealing its role in spatial navigation and short- and long-term memory formation. The pioneering work of O’Keefe and that of many other laboratories revealed that hippocampal pyramidal cells (PCs) increase their firing in certain locations of the environment (place cells), and that the entire space is covered by the place fields of many different place cells. In a given environment, only a small fraction of PCs are active. Thus, an environment is represented by a unique combination of cells (assembly). Recent studies addressed the issue of how large is the overlap between neuronal representations/assemblies of distinct spatial environments. They revealed that the assembly representing an environment contains few place cells with multiple place fields and high firing rates in their place fields and numerous other place cells with a single place field in the environment with much lower firing rates. When the animals is placed in a new environment, the probability of the previously highly active neurons remain part of the new ensemble is high, whereas the less active cells have a very low probability to be part of the new representation. So far, no information is available regarding the mechanism underlying the morphological, physiological and molecular mechanisms underlying low and high place field propensity of the PCs. The Laboratory of Cellular Neurophysiology tests the hypothesis that enhanced intrinsic electrical excitability together with increased synaptic weights characterize CA1 PCs that consistently participate in multiple spatial representations. In vivo two-photon imaging are conducted in awake, headrestrained mice while performing navigation in virtual environments to characterize CA1 PCs during behaviour. Post hoc, in vitro patch-clamp experiments are performed to characterize the intrinsic electrical properties and the synaptic inputs of the imaged cells. Finally, post hoc anatomical analysis is performed to reveal the morphology of the cells and their molecular content.