Input-output properties of neurons generated in the adult hippocampus



The dentate gyrus of the mammalian hippocampus generate neurons throughout life. Developing granule cells (GCs) require 6-8 weeks to reach functional maturity. It has recently been proposed that developing (immature) GCs might play a critical role in information processing. However, whether young GCs can integrate afferent signals to produce an output remains unknown, and the output of new GCs has never been characterized. We have studied input-output conversion in developing GCs of the adult mouse hippocampus. Glutamatergic inputs onto young neurons are very weak compared to those of mature cells, yet stimulation of cortical excitatory axons elicits a similar spiking probability in neurons at either developmental stage. Young neurons are highly efficient in transducing ion fluxes into membrane depolarization due to their high input resistance, which decreases substantially in mature neurons due to the delayed expression of a potassium conductance, with a consequent reduction in intrinsic excitability.
To study neurotransmitter release, new GCs were transduced with light-activated cation channel Channelrhodopsin 2 (ChR2) and a fluorescent reporter gene. Blue light elicited spikes in GCs expressing ChR2. Postsynaptic responses were then assessed in randomly selected hilar interneurons. About 10% of >110 neurons reliably displayed postsynaptic currents (PSCs) in response to light pulses delivered to fluorescent GCs in the slice. PSCs were blocked by glutamate receptor antagonists, indicating that adult-born GCs make functional synaptic contacts and release glutamate as their main neurotransmitter. Therefore, newly generated CGs can integrate, process and convey information onto target cells in the adult dentate gyrus.