Josef Bischofberger

In the adult hippocampus new neurons are continuously generated throughout life. The newly generated young neurons show a number of distinct functional properties, including enhanced excitability, reduced GABAergic inhibition and enhanced synaptic plasticity (Lodge and Bischofberger 2019). Based on these cell biological findings it was concluded that the young neurons are hyperactive and hyperexcitable during learning behavior and memory processing. However, on the behavioral level adult neurogenesis improves learning by increasing the brains capability to distinguish between similar memory items, a process called “pattern separation”. We use synaptic circuit analysis in acute brain slices vitro and miniscope calcium imaging in vivo, to address this apparent paradox of “hyperactive cells” versus “improved pattern separation”.

We have studied excitatory glutamatergic synaptic transmission onto newly generated young granule cells (GCs, Li et al. 2017) showing that the young neurons fire action potentials (APs) as early as 2 weeks post mitosis in response to a small number of active synapses, due to a high synaptic gain. However, due to small dendritic trees and sparse connectivity, neighbouring young neurons are activated by different distinct subsets of afferent fibers with minimal overlap. As the neurons mature, the increase in synapse number is balanced by a gradual decrease in intrinsic excitability. This indicates that the enhanced excitability in young granule cells does not generate hyperexcitability, but instead compensates for sparse synaptic connectivity in developing young neurons. Furthermore, young neurons are controlled by powerful GABAergic synaptic inhibition as early as 2 wpm (Lodge et al. 2021). Therefore, perforant-path fibers can recruit young neurons in a sparse and orthogonal manner.

Using calcium imaging in vivo, we are currently investigating how these circuit properties support sparse coding and information processing during hippocampus-dependent learning and memory retrieval.