FUNCTIONAL INTEGRATION OF NEW NEURONS INTO THE ADULT HIPPOCAMPAL CIRCUITRY

SCHINDER AF

Lisboa, Portugal

Congreso; Howard Hughes Medical Institute Meeting of International Research Scholars; 2008

Howard Hughes Medical Institute

The adult brain contains neural stem cells that can generate neurons throughout life. In mammals, adult neurogenesis is restricted to the olfactory bulb and the dentate gyrus of the hippocampus, a cortical structure involved in learning and memory. In the past, we have combined in-vivo retroviral labeling with electrophysiology and confocal microscopy to express GFP in new granule cells (GCs) of the adult hippocampus to study their anatomical and functional maturation, a process lasting several weeks. 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 with a consequent reduction in excitability. Mechanisms underlying these changes in excitability during maturation of adult-born GCs are currently being addressed. To study neurotransmitter release, new GCs were transduced with a retrovirus encompassing the 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.