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

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 brain. 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 formation. 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 period. Spine dynamics were measured in the forebrain nucleus HVC, the proximal site where auditory information merges with an explicit song motor representation, immediately before and after juvenile finches first experienced tutor song. 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.

[1]  Paul Henman.  Targeted! , 2004 .

[2]  F. Nottebohm,et al.  Dynamics of the Vocal Imitation Process: How a Zebra Finch Learns Its Song , 2001, Science.

[3]  Daniel Margoliash,et al.  Sleep and sensorimotor integration during early vocal learning in a songbird , 2008, Nature.

[4]  Mriganka Sur,et al.  Motility of dendritic spines in visual cortex in vivo: Changes during the critical period and effects of visual deprivation , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[5]  Marguerita E Klein,et al.  Telencephalic Neurons Monosynaptically Link Brainstem and Forebrain Premotor Networks Necessary for Song , 2008, The Journal of Neuroscience.

[6]  W. Denk,et al.  Lentivirus-based genetic manipulations of cortical neurons and their optical and electrophysiological monitoring in vivo , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[7]  Bernardo L Sabatini,et al.  Anatomical and physiological plasticity of dendritic spines. , 2007, Annual review of neuroscience.

[8]  G. Shepherd,et al.  Transient and Persistent Dendritic Spines in the Neocortex In Vivo , 2005, Neuron.

[9]  L. A. Eales.  Song learning in zebra finches: some effects of song model availability on what is learnt and when , 1985, Animal Behaviour.

[10]  K. Svoboda,et al.  Rapid dendritic morphogenesis in CA1 hippocampal dendrites induced by synaptic activity. , 1999, Science.

[11]  Roberto Malinow,et al.  Glutamate Receptor Exocytosis and Spine Enlargement during Chemically Induced Long-Term Potentiation , 2006, The Journal of Neuroscience.

[12]  Bartlett W. Mel,et al.  Cortical rewiring and information storage , 2004, Nature.

[13]  Yi Zuo,et al.  Long-term sensory deprivation prevents dendritic spine loss in primary somatosensory cortex , 2005, Nature.

[14]  T. Bonhoeffer,et al.  Experience leaves a lasting structural trace in cortical circuits , 2008, Nature.

[15]  W. Gan,et al.  Development of Long-Term Dendritic Spine Stability in Diverse Regions of Cerebral Cortex , 2005, Neuron.

[16]  F. Nottebohm,et al.  Central control of song in the canary, Serinus canarius , 1976, The Journal of comparative neurology.

[17]  F. Nottebohm,et al.  Targeted Neuronal Death Affects Neuronal Replacement and Vocal Behavior in Adult Songbirds , 2000, Neuron.

[18]  Jonathan F Prather,et al.  A Synaptic Basis for Auditory–Vocal Integration in the Songbird , 2008, The Journal of Neuroscience.

[19]  Karel Svoboda,et al.  Rapid Functional Maturation of Nascent Dendritic Spines , 2009, Neuron.

[20]  K. D. Punta,et al.  An ultra-sparse code underlies the generation of neural sequences in a songbird , 2002 .

[21]  K. Svoboda,et al.  Long-term in vivo imaging of experience-dependent synaptic plasticity in adult cortex , 2002, Nature.

[22]  J. S. McCasland,et al.  Interaction between auditory and motor activities in an avian song control nucleus. , 1981, Proceedings of the National Academy of Sciences of the United States of America.

[23]  F. Engert,et al.  Dendritic spine changes associated with hippocampal long-term synaptic plasticity , 1999, Nature.

[24]  J. F. Prather,et al.  Precise auditory–vocal mirroring in neurons for learned vocal communication , 2008, Nature.

[25]  P. Mitra,et al.  How sleep affects the developmental learning of bird song , 2005, Nature.

[26]  G. Ellis‐Davies,et al.  Structural basis of long-term potentiation in single dendritic spines , 2004, Nature.

[27]  Karel Svoboda,et al.  Experience-dependent and cell-type-specific spine growth in the neocortex , 2006, Nature.

[28]  R. Mooney.  Different Subthreshold Mechanisms Underlie Song Selectivity in Identified HVc Neurons of the Zebra Finch , 2000, The Journal of Neuroscience.

[29]  Dominique Muller,et al.  LTP Promotes a Selective Long-Term Stabilization and Clustering of Dendritic Spines , 2008, PLoS biology.