Scientific Understanding of Consciousness
Consciousness as an Emergent Property of Thalamocortical Activity

Dendritic Spines and Memories


Nature 462, 920-924 (17 December 2009)

Stably maintained dendritic spines are associated with lifelong memories

Guang Yang, Feng Pan & Wen-Biao Gan

Molecular Neurobiology Program, The Helen and Martin Kimmel Center for Biology and Medicine at the Skirball Institute of Biomolecular Medicine, Department of Physiology and Neuroscience, New York University School of Medicine, New York, New York 10016, USA


Changes in synaptic connections are considered essential for learning and memory formation. However, it is unknown how neural circuits undergo continuous synaptic changes during learning while maintaining lifelong memories. Here we show, by following postsynaptic dendritic spines over time in the mouse cortex, that learning and novel sensory experience lead to spine formation and elimination by a protracted process. The extent of spine remodelling correlates with behavioural improvement after learning, suggesting a crucial role of synaptic structural plasticity in memory formation. Importantly, a small fraction of new spines induced by novel experience, together with most spines formed early during development and surviving experience-dependent elimination, are preserved and provide a structural basis for memory retention throughout the entire life of an animal. These studies indicate that learning and daily sensory experience leave minute but permanent marks on cortical connections and suggest that lifelong memories are stored in largely stably connected synaptic networks.

One remarkable feature of the mammalian brain is its capacity to integrate new information throughout life while stably maintaining memories. Coincident with these two seemingly mutually exclusive attributes of the brain are plasticity and stability of synaptic connections. It is well-established that the strength and number of synaptic connections can undergo rapid and extensive changes after sensory alterations and learning throughout life. On the other hand, recent studies have shown that dendritic spines, the postsynaptic sites of excitatory synapses, are remarkably stable in adult life. Therefore, synaptic connections are not only capable of undergoing rapid changes in response to new experience but also can serve as substrates for long-term information storage. However, it remains unknown how and to what degree synapses reorganize during learning and how such reorganization is transformed into lifelong memories.

To address these questions, we used transcranial two-photon microscopy to examine how fluorescently labelled dendritic spines of layer V pyramidal neurons in the mouse cortex are altered and maintained in response to skill learning or novel sensory experience.

Many lines of evidence indicate that developmental change in synapse number is remarkably similar across different cortical layers and regions in a variety of species. We found that in the dendrites of layer V and VI pyramidal neurons in mouse barrel cortex, the number of spines rose rapidly after birth, underwent a substantial net loss during late postnatal life and declined slowly throughout adulthood. Importantly, in the apical dendrites of layer V pyramidal cells, we found that the substantial net loss of spines during postnatal development was due to a combination of two factors: (1) a tremendous burst in spine formation early in life was followed by a rapid decline in spine formation from P19 to P30; and (2) regardless of developmental stages, only a small fraction of newly formed spines were maintained by a similar prolonged process.

Here we show that, despite ongoing circuit plasticity,    two populations of stable spines are important for maintaining lifelong memories. Specifically, our findings suggest that a minute fraction of new spines (~0.04% of total spines) induced by novel experience, together with spines formed early during development and remaining after experience-dependent pruning, represent a unique and stable physical entity for lifelong memory storage. The fact that most spines in such an entity persist underscores the fundamental importance of stably connected synaptic circuits in lifelong memory storage.

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Nature 462, 915-919 (17 December 2009) | doi:10.1038/nature08389; Received 7 April 2009; Accepted 6 August 2009; Published online 29 November 2009

Rapid formation and selective stabilization of synapses for enduring motor memories

Tonghui Xu1,3, Xinzhu Yu1,3, Andrew J. Perlik1, Willie F. Tobin1, Jonathan A. Zweig1, Kelly Tennant2, Theresa Jones2 & Yi Zuo1

Department of Molecular, Cell and Developmental Biology, University of California Santa Cruz, Santa Cruz, California 95064, USA

Institute for Neuroscience, Department of Psychology, University of Texas at Austin, Austin, Texas 78712, USA


Novel motor skills are learned through repetitive practice and, once acquired, persist long after training stops. Earlier studies have shown that such learning induces an increase in the efficacy of synapses in the primary motor cortex, the persistence of which is associated with retention of the task. However, how motor learning affects neuronal circuitry at the level of individual synapses and how long-lasting memory is structurally encoded in the intact brain remain unknown. Here we show that synaptic connections in the living mouse brain  rapidly respond to motor-skill learning and permanently rewire. Training in a forelimb reaching task leads to rapid (within an hour) formation of postsynaptic dendritic spines on the output pyramidal neurons in the contralateral motor cortex. Although selective elimination of spines that existed before training    gradually returns the overall spine density    back to the original level,    the new spines induced during learning are preferentially stabilized during subsequent training and endure long after training stops. Furthermore, we show that different motor skills are encoded by different sets of synapses. Practice of novel, but not previously learned, tasks further promotes dendritic spine formation in adulthood. Our findings reveal that rapid, but long-lasting, synaptic reorganization is closely associated with motor learning. The data also suggest that stabilized neuronal connections are the foundation of durable motor memory.

Fine motor movements require accurate muscle synergies that rely on coordinated recruitment of intracortical synapses onto corticospinal neurons. Obtaining new motor skills has been shown to strengthen the horizontal cortical connections in the primary motor cortex. In this study, we taught mice a single-seed reaching task. The majority of 1-month-old mice that underwent training gradually increased their reaching success rates during the initial 4 days, and then levelled off (n = 42). There were a few mice (n = 5) that engaged in extensive reaching, but continually failed to grasp the seeds. These mice normally gave up reaching after 4–8days. To investigate the process of learning-induced synaptic remodelling in the intact motor cortex, we repeatedly imaged the same apical dendrites of layer V pyramidal neurons marked by the transgenic expression of yellow fluorescent protein (YFP-H line) in various cortical regions during and after motor learning, using transcranial two-photon microscopy. Dendritic spines are the postsynaptic sites of most excitatory synapses in the brain and changes in spine morphology and dynamism serve as good indicators of synaptic plasticity.

One of the important characteristics of motor learning is that, once the skill is well learned, its further maintenance does not require constant practice.

Despite high spine dynamics induced by novel skill learning, most spines that were formed during adolescent learning and maintained in adults  persisted after training with the handling task (95.6±7.7%), suggesting that already stabilized synapses are not perturbed by novel learning in adults. These results indicate that synaptic structural coding  outlasts the early learning experience and persists in adulthood to support later maintenance of motor skills. The fact that novel learning experiences continue to drive synaptic reorganization  without affecting the stability of synapses formed during previous learning further suggests that different motor behaviours are stored using different sets of synapses in the brain.

Our in vivo imaging of superficial dendrites from layer V pyramidal neurons revealed that postsynaptic dendritic spine addition was rapid, but eventually counteracted by the loss of pre-existing spines, resulting in a time-dependent spine density change during motor learning. Although the synaptogenesis observed in our study is compatible with earlier results, its temporal relationship with behavioural improvement and the contribution of synapse elimination in circuitry reorganization in other brain layers and regions during motor learning require further investigation. This eventual balancing of synapse number could be a homeostatic mechanism by which the output layer V neurons  integrate converging inputs into superficial cortical layers to govern precise fine motor control.

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Nature 462, 1065-1069 (24 December 2009)

Secreted semaphorins control spine distribution and morphogenesis in the postnatal CNS

Tracy S. Tran, Maria E. Rubio, Roger L. Clem, Dontais Johnson, Lauren Case, Marc Tessier-Lavigne, Richard L. Huganir, David D. Ginty & Alex L. Kolodkin

Solomon H. Snyder Department of Neuroscience,

Howard Hughes Medical Institute, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA

Departments of Physiology and Neurobiology, University of Connecticut, Storrs, Connecticut 06269, USA

Graduate Program in Neurosciences, Stanford University, Stanford, California 94305, USA

Division of Research, Genentech, South San Francisco, California 94080, USA


The majority of excitatory synapses in the mammalian CNS (central nervous system) are formed on dendritic spines, and spine morphology and distribution are critical for synaptic transmission, synaptic integration and plasticity. Here, we show that a secreted semaphorin, Sema3F, is a negative regulator of spine development and synaptic structure. Mice with null mutations in genes encoding Sema3F, and its holoreceptor components neuropilin-2 (Npn-2, also known as Nrp2) and plexin A3 (PlexA3, also known as Plxna3), exhibit increased dentate gyrus (DG) granule cell (GC) and cortical layer V pyramidal neuron spine number and size, and also aberrant spine distribution. Sema3F signalling    controls spine distribution    along select dendritic processes,    and distinct secreted semaphorin signalling events    orchestrate CNS connectivity    through the differential control of spine morphogenesis,    synapse formation,    and the elaboration of dendritic morphology.

The organization and distribution of excitatory synapses along primary, secondary and higher order dendritic branches defines how presynaptic inputs are integrated into neural networks. Thus, the precise control of both excitatory and inhibitory synapse distribution during neural development is essential for the formation of functional circuits. Our finding that Sema3F controls the spatial distribution of spines along apical dendrites of cortical pyramidal and hippocampal granule neurons indicates that this secreted cue is essential for integration of excitatory inputs onto these neurons.

These findings underscore the necessity of understanding the mechanisms underlying Sema3F–Npn-2/PlexA3 control of differential spine growth and distribution, and Sema3A–Npn-1/PlexA4 control of basal dendrite growth. Npn-2 is localized to the PSD and we show here that the Npn-2 PDZ domain-binding motif is essential for Sema3F responsiveness. The precise localization of Sema3 holoreceptor complexes via one or more PDZ scaffold proteins associated with postsynaptic components may serve to provide directed Sema3 signalling to subcellular dendritic compartments, regulating dendritic spine morphology and spatial distribution of synapses.

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