Development, plasticity and ensemble recruitment of AcD cells in the hippocampus

• Applicants: Privatdozent Dr. Martin Both; Dr. Maren Engelhardt
• Subject Area: Molecular Biology and Physiology of Neurons and Glial Cells
• Term: from 2019 to 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 427956063

The hippocampus is important for the formation of episodic and semantic memory. To achieve this, it generates distinct network oscillations, during which groups of neurons – functional ensembles – are activated specifically. This activation has the following principle: dendritic excitatory synaptic potentials that remain below threshold to elicit an action potential (AP) are integrated at the soma and directed towards the axon, which emanates at the soma. At the axon initial segment, an AP is then generated. At various points along this pathway, inhibitory signals may elicit constrain on this integration. Of particular interest is perisomatic inhibition that targets the soma specifically.Recently, we showed that in about 50 % of principal neurons, the morphology of axon onset deviates from the above mentioned principle (axon at soma). Instead, the axon emerges off a basal dendrite. This basal dendrite is more effective in converting excitatory potentials into APs than other dendrites. In addition, this morphological phenotype may have another consequence at the network level: excitatory potentials at the axon-carrying dendrite can elicit APs by circumventing perisomatic inhibition, while all other incoming signals are attenuated significantly. We already verified this hypothesis in an in vitro model of network oscillations. Now, we plan to investigate if the morphological differences between neurons allow for a novel and fundamental mechanism, which controls the integration and propagation of information via perisomatic inhibition. This is relevant since different states of consciousness, e.g. the retrieval of memories, depends on specific network rhythms, which recruit distinct inhibition. In this context, it is important to understand when and how these specific neurons are developed (for example via genetic programs or possibly by brain activation patterns in a self-regulatory manner). Finally, we want to study whether morphologically distinct neurons are integrated into the existing network differently. Do they have different presynaptic partners or postsynaptic targets? Is their local connectivity, particularly with inhibitory neurons, different?In summary, we aim at investing how cellular mechanisms and morphologies contribute to regulate functional ensembles in dependence of the conscious state. In this context, neurons with axon-carrying dendrites might represent a privileged group of cells with hitherto unknown functions.

• DFG Programme: Research Grants