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Rapid spine stabilization and synaptic enhancement at the onset of behavioural learning

Abstract

Behavioural learning depends on the brain’s capacity to respond to instructive experience and is often enhanced during a juvenile sensitive period. How instructive experience acts on the juvenile brain to trigger behavioural learning remains unknown. In vitro studies show that forms of synaptic strengthening thought to underlie learning are accompanied by an increase in the stability, number and size of dendritic spines, which are the major sites of excitatory synaptic transmission in the vertebrate brain1,2,3,4,5,6,7. In vivo imaging studies in sensory cortical regions reveal that these structural features can be affected by disrupting sensory experience and that spine turnover increases during sensitive periods for sensory map formation8,9,10,11,12. These observations support two hypotheses: first, the increased capacity for behavioural learning during a sensitive period is associated with enhanced spine dynamics on sensorimotor neurons important for the learned behaviour; second, instructive experience rapidly stabilizes and strengthens these dynamic spines. Here we report a test of these hypotheses using two-photon in vivo imaging to measure spine dynamics in zebra finches, which learn to sing by imitating a tutor song during a juvenile sensitive period13,14. Spine dynamics were measured in the forebrain nucleus HVC, the proximal site where auditory information merges with an explicit song motor representation15,16,17,18,19, immediately before and after juvenile finches first experienced tutor song20. Higher levels of spine turnover before tutoring correlated with a greater capacity for subsequent song imitation. In juveniles with high levels of spine turnover, hearing a tutor song led to the rapid (24-h) stabilization, accumulation and enlargement of dendritic spines in HVC. Moreover, in vivo intracellular recordings made immediately before and after the first day of tutoring revealed robust enhancement of synaptic activity in HVC. These findings suggest that behavioural learning results when instructive experience is able to rapidly stabilize and strengthen synapses on sensorimotor neurons important for the control of the learned behaviour.

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Figure 1: Examining how tutor song affects spine turnover in juvenile zebra finches.
Figure 2: Levels of HVC dendritic spine turnover correlate with song imitation.
Figure 3: Tutoring can trigger rapid stabilization and accumulation of dendritic spines on HVC neurons.
Figure 4: Tutoring triggers enlargement of stable dendritic spines in HVC.
Figure 5: Tutoring triggers enhancement of spontaneous synaptic activity in HVC.

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Acknowledgements

We thank M. Ehlers and L. Katz for access to the two-photon microscope and support in making lentivirus, K. Hamaguchi for peak detection and analysis software and D. Kloetzer for animal husbandry and laboratory support. D. Fitzpatrick, D. Purves and M. Ehlers provided comments on the manuscript. This work was supported by grants from the US National Science Foundation (NSF) and the US National Institutes of Health (NIH) (R.M.). T.F.R. was supported by a National Research Service Award from the NIH, K.A.T. was supported by a pre-doctoral award from the NSF and M.E.K. was supported by the Howard Hughes Medical Institute (Investigator, M. Ehlers).

Author Contributions T.F.R. and R.M. designed the study and wrote the manuscript. T.F.R. and K.A.T. collected and analysed the imaging and behavioural data. T.F.R. and M.E.K. designed the lentiviral construct and M.E.K. made the lentivirus. T.F.R and R.M. collected the electrophysiological data.

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Correspondence to Richard Mooney.

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Roberts, T., Tschida, K., Klein, M. et al. Rapid spine stabilization and synaptic enhancement at the onset of behavioural learning. Nature 463, 948–952 (2010). https://doi.org/10.1038/nature08759

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