Figure 7.

Model showing how increasing adult hippocampal neurogenesis modulates DG excitability while maintaining output to CA3c (A). In control animals, adult-born and mature dentate granule neurons exert feed-back inhibition onto mature dentate granule neurons through excitatory contacts with hilar interneurons. Young adult-born dentate granule neurons are insensitive to this feed-back inhibition. The extent of DG activation dictates the strength of feed-forward excitation and di-synaptic feed-forward inhibition to CA3c mediated by excitatory contacts of mature and adult-born dentate granule neurons onto CA3c neurons and CA3c neurons via SL interneurons, respectively. (B) When the number of adult-born dentate granule neurons is increased, excitatory drive onto hilar interneurons is increased, thereby increasing feed-back inhibition onto mature dentate granule neurons. Consequently, feed-forward excitation and di-synaptic feed forward inhibition to CA3c mediated by mature dentate granule neurons is decreased. However, feed-forward excitation and di-synaptic feed forward inhibition mediated by adult-born dentate granule neurons to CA3c is increased. Thus, the integration of young adult-born dentate granule neurons into the DG-CA3 circuit directly and indirectly dictates the extent to which feed forward excitation and inhibition is recruited by young adult-born and mature dentate granule neurons, respectively, to activate CA3c. IN: hilar or stratum lucidum interneuron, EC, entorhinal cortex; mf, mossy fiber; MC, mossy cell. Size of line indicates strength of connection.