Immature neurons are preferentially activated in the dentate gyrus of adult mice

LUCAS A. MONGIAT; M. BELÉN PARDI; ANTONIA MARÍN-BURGIN; ALEJANDRO F. SCHINDER

Washington DC

Congreso; Society for Neuroscience 2011; 2011

Society for Neuroscience

Adult neurogenesis provides a continuous pool of new granule cells (GCs) to the dentate gyrus (DG) of the hippocampus. Immature GCs exhibit elevated excitability and increased synaptic plasticity at their input synapses. These properties led us to investigate whether immature GCs are differently activated by entorhinal inputs, as compared to preexistent mature neurons in the DG. For this purpose, we performed experiments to determine the network recruitment of immature (four weeks old) vs. mature (> eight weeks old) GCs. Briefly, adult-born neurons were labeled by retroviral injections and mice were euthanized at 4 (immature) or >8 weeks (mature) after injection, and hippocampal slices were obtained and maintained in ACSF. Loose-patch voltage clamp recordings were performed in fluorescently labeled GCs to assess spiking probability elicited by perforant path stimulation. We found that four-week-old GCs evoked spikes at a range of low stimulus intensities, whereas higher stimulation amplitudes were needed to activate mature neurons. Moreover, application of the GABAA antagonist picrotoxin (100µM) induced a shift in the recruitment of mature GCs towards weaker stimulus intensities, in a way that resembled the activation profile of immature neurons. Interestingly, the four-week-old GC population resulted insensitive to picrotoxin. These results indicate that immature neurons are preferentially activated due to a weaker inhibitory control. We are currently investigating the precise contribution of excitatory and inhibitory afferents to young and mature GCs.