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Activation of adult-born neurons facilitates learning and memory

Abstract

Thousand of local interneurons reach the olfactory bulb of adult rodents every day, but the functional effect of this process remains elusive. By selectively expressing channelrhodopsin in postnatal-born mouse neurons, we found that their activation accelerated difficult odor discrimination learning and improved memory. This amelioration was seen when photoactivation occurred simultaneously with odor presentation, but not when odor delivery lagged by 500 ms. In addition, learning was facilitated when light flashes were delivered at 40 Hz, but not at 10 Hz. Both in vitro and in vivo electrophysiological recordings of mitral cells revealed that 40-Hz stimuli produced enhanced GABAergic inhibition compared with 10-Hz stimulation. Facilitation of learning occurred specifically when photoactivated neurons were generated during adulthood. Taken together, our results demonstrate an immediate causal relationship between the activity of adult-born neurons and the function of the olfactory bulb circuit.

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Figure 1: Light-induced activation of adult-born neurons.
Figure 2: Olfactory discrimination learning.
Figure 3: Stimulation of adult-born neurons accelerates learning.
Figure 4: Light-induced responses in granule and mitral cells in vitro.
Figure 5: Light-activation of ChR2-positive adult-born neurons control spontaneous and odor-evoked mitral cell firing activity in the awake mouse.
Figure 6: Light stimulation of postnatal-born neurons does not modify odor discrimination learning.

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Acknowledgements

We thank G. Gheusi for his advice regarding the use of olfactometers, L. Petreanu for the manipulation of the LEDs during behavioral experiments, K. Murray and N. Maffey for technical assistance, and M. Valley and G. Gheusi for their critical reading of the manuscript. We thank the ENP Network for Viral Transfer for viral vector production. This work was supported by NovalisTaitbout, the Letten Foundation, the Foundation pour la Recherche Medical, the Agence Nationale de la Recherche (ANR-BLAN-SVSE4-LS-110624 and ANR-09-NEUR-004 in the frame of “ERA-NET NEURON” of FP7 program by the European Commission).

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Authors

Contributions

M.A. and P.-M.L. designed the experiments, discussed the results and wrote the manuscript. M.A. performed surgery, behavioral experiments and analyzed data. G.L. designed, performed and analyzed in vivo electrophysiology recordings. S.W. design olfactomers and light-stimulation devices. C.B. performed and analyzed in vitro electrophysiology recordings. M.-M.G. performed immunohistochemistry and N.T. designed the database for behavioral analysis.

Corresponding author

Correspondence to Pierre-Marie Lledo.

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The authors declare no competing financial interests.

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Supplementary Video 1

Photostimulation of adult-born neurons during olfactory discrimination learning. (AVI 10250 kb)

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Alonso, M., Lepousez, G., Wagner, S. et al. Activation of adult-born neurons facilitates learning and memory. Nat Neurosci 15, 897–904 (2012). https://doi.org/10.1038/nn.3108

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