High frequency filters with variable gain in the dentate gyrus generated by differential inhibition onto developing and mature granule cells of the adult hippocampus.

MA. BELEN PARDI; MORA B. OGANDO; ALEJANDRO F. SCHINDER; ANTONIA MARIN BURGIN

Chicago

Congreso; Society for Neurosciences; 2015

Adult neurogenesis generates pools of constantly renewing immature granule cells (GC) with unique processing properties. We have previously showed that immature GC have lower thresholds of activation than the rest of the GC from the circuit, 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 (4wpiGC). 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 the GC receives after the stimulation. Thus, activity arriving to the hippocampus at different frequencies activates two populations of neurons with variable frequency filters, immature cells, with wide range of responses, that are reliable transmitters of the incoming frequency, and mature neurons, with narrow responses to frequency and sparse activity.