Frequency dependent activation of immature and mature granule cells in the adult hippocampus.

PARDI M. BELÉN; SCHINDER ALEJANDRO F.; MARIN-BURGIN ANTONIA

Congreso; 12th Meeting of the French Neuroscience Society; 2015

Adult neurogenesis generates pools of constantly renewing immature granule cells (GC) with unique processing properties. We have previously shown that immature GC have lower thresholds of activation than the rest of the GC from the dentate gyrus, already mature. In the present work we address the question of how immature and mature granule cells process complex stimuli in the form of trains of pulses at different frequencies, and how activation profiles are determined by the recruitment of inhibitory and excitatory circuits. To study activation of immature newly born cells in the adult hippocampus, we inject a retrovirus in the dorsal hippocampus of adult mice to label dividing cells. Four weeks later, we prepare acute hippocampal slices from the injected mice, where we can recognize the immature four week old adult born granule cells (4wpi GC). By simulating the afferent medial perforant path with a monopolar electrode and recording from 4wpi GC and mature GC with loose-patch and whole-cell configurations we studied spiking, and evoked excitatory and inhibitory currents after 1 Hz, 10 Hz, 20 Hz and 40 Hz trains of stimulation. Results show that 4wpi GC are activated at higher levels than mature GC at every frequency of stimulation. Moreover, 4wpiGC are more efficient in reproducing the frequency of stimulation with their spiking. Activation levels strikingly diminish at higher frequencies, showing that both populations of GC act as low-pass filters. Main differences in the activation profiles are dictated by the inhibitory circuits. Inhibition determines activation by affecting the excitation/inhibition balance that the GC receive after the stimulation. Feed-forward inhibition generates both differences in activation between 4wpi GC and mature GC, and differences between frequencies. On the contrary, feed-back inhibition only affects differences in activation among frequencies. Hence, results show that 4wpi GC have an important participation in the dentate gyrus activation after physiologically relevant stimulation, which is generated by a higher excitation/inhibition balance than mature GC, due to a slower and smaller recruited feed-forward inhibition.