Reliable Activation of Immature Neurons in the Adult Hippocampus

MONGIAT, LUCAS A; MARÍN BURGIN, ANTONIA; SCHINDER, ALEJANDRO F

Huerta Grande, Córdoba, Argentina

Congreso; I Reunión Conjunta de Neurociencias; 2009

Sociedad Argentina de Investigación en Neurociencias - Taller Argentino de Neurociencias

  Neurons born in the adult dentate gyrus develop, mature, and connect over a long interval that last from six to eight weeks. It has been proposed that, while developing, young neurons play a relevant role in hippocampal signal processing owing to their distinctive electrical properties. However, it has remained unknown whether immature neurons can be recruited into a network before synaptic and functional maturity has been achieved. To address this question, we used retroviral expression of GFP to identify developing granule cells of the adult mouse hippocampus. We investigated on young and mature dentate granule cells the balance between afferent excitation and inhibition, intrinsic excitability, and recruitment into the hippocampal circuitry using patch clamp recordings in acute slices.   We found that young neurons receive weaker excitatory inputs than mature dentate granule cells. By the hand, young neurons are intrinsically more excitable than mature neurons and are highly efficient in transducing ionic currents into membrane depolarization due to their high input resistance, which decreases substantially in mature neurons as the inward rectifier potassium (Kir) conductance increases. Next we evaluated how young neurons integrate a lower glutamatergic input with their enhanced excitability. To answer this question we evaluated spiking probability evoked by stimulation of excitatory afferents in the presence of GABA receptor antagonists. Under these conditions we found that young and mature neurons exhibited similar firing behavior, indicating that the differences in excitatory drive of young and mature neurons are compensated by changes in membrane excitability rendering an equalized firing activity. In addition, we evaluated how the inhibitory circuitry impinges onto this balanced firing between young and mature DGCs. We found that young neurons shows a lower threshold of activation in response to an excitatory drive delivered to the perforant-path. However, by blocking the GABAergic contribution to the circuitry, the firing behavior of young and mature neurons becomes equalized. These results indicate that adult hippocampal neurogenesis contributes with a continuous population of young neurons which are preferentially recruited tou the hippocampal network.