Spine plasticity in the motor cortex
Introduction
The mammalian cortex is composed of columnar aggregates of neurons that share similar functional properties, such as orientation selectivity in the visual cortex or muscle movement control in the motor cortex. Functional maps in different cortical regions are capable of rapid and long-lasting reorganization throughout the animal's life, which is associated with novel experiences and pathologies. In the motor cortex, learning a new motor task is accompanied by expansion of the functional representation of task-related muscle movements in rats, primates and humans [1, 2, 3]. During the recovery following stroke or injury, surviving cortical regions adopt the function of damaged tissues [4, 5, 6]. In the visual cortex, the retinotopic map remodels following retinal lesions, associated with a massive rewiring of synaptic structures [7•]. It has been proposed that intrinsic horizontal connections (i.e., intercolumnar and intracolumnar connections) of the cerebral cortex serve as a structural substrate for map plasticity. Pyramidal neurons establish these connections by extending long, horizontal axon collaterals that form excitatory synapses with their postsynaptic partners.
The synapse is the site of information exchange in the central nervous system. In the mammalian brain, the vast majority of excitatory glutamatergic synapses are formed between presynaptic axonal en passant boutons and postsynaptic dendritic spines. Dendritic spines are small protrusions emanating from dendritic shafts. Not only are spines heterogeneous in shape, their density also varies among different types of neurons and in different developmental stages [8]. Spines contain all the essential components required for postsynaptic signaling and plasticity and, thus, serve as good indicators of modifications in synaptic connectivity [9, 10, 11]. Recent studies have revealed dynamics of individual, fluorescently labeled dendritic spines over time in various cortical regions of living mice using two-photon imaging, and demonstrated that sensory experience dramatically affects spine stability (see reviews [12, 13, 14]). However, relatively little is known about spine dynamics in the motor cortex, how motor learning affects the connectivity of the neural circuitry, or how memory is structurally encoded in the intact brain.
Here, we will first review earlier studies on the functional and structural plasticity of synapses in the mammalian motor cortex. Next, we will move to the living brain and discuss recent examinations of spine dynamics during development and learning, including a comparative analysis of different cortical regions. Finally we will talk about some in vitro and in vivo studies on altered spine morphology and dynamics under pathological conditions.
Section snippets
Functional plasticity of synapses
Integration of synaptic signals is critical to the functional organization of neural circuitry. Long-term potentiation (LTP) and long-term depression (LTD) lead to changes in synaptic efficacy and have been proposed to be candidate mechanisms for learning-induced plasticity in the motor cortex. Evidence supporting this hypothesis comes from studies on both animals and humans. Training rats with a skilled reaching task has been shown to strengthen horizontal connections in both layer I and layer
Spine dynamics in the living brain
The advent of high-resolution time-lapse imaging in conjunction with fluorescent molecular tools enables the visualization of synaptic structures in living animals. Using two-photon microscopy and transgenic animals in which a small population of neurons is fluorescently labeled, turnover and morphological changes of postsynaptic dendritic spines have been examined in various cortical regions, both during development and in association with experience and learning. While long-term in vivo
Altered spine morphology and dynamics under pathologies
While experience-dependent modification of spine plasticity provides a cellular mechanism underlying learning and memory, abnormal spine morphology and dynamics are hallmarks of injuries and neurological diseases. In Alzheimer's disease (AD), a dramatic spine loss has been observed in the vicinity of β-amyloid plaques in the living cortex of transgenic AD mice [42, 43]. Fragile X Syndrome (FXS) is characterized by an abundance of immature postsynaptic dendritic spines. A recent study has
Conclusion
An important feature of the mammalian cortex is the capability of rapid and long-lasting functional reorganization. Our understanding of the morphological plasticity of spines, as well as their modifications with learning and altered brain functions in the living cerebral cortex, highlights the significance of spines in the functional reorganization. In the motor system, current in vivo evidence indicates that spinogenesis occurs rapidly after motor learning is initiated and that a large
References and recommended reading
Papers of particular interest, published within the period of review, have been highlighted as:
• of special interest
•• of outstanding interest
Acknowledgements
We thank David States and Drs. Ju Lu, Denise Garcia for critical comments on this manuscript. This work was supported by grants from the Ellison Medical Foundation, the DANA Foundation, and the National Institutes of Aging to Y.Z.
References (54)
Mechanisms for recovery of motor function following cortical damage
Curr Opin Neurobiol
(2006)- et al.
Molecular mechanisms of dendritic spine morphogenesis
Curr Opin Neurobiol
(2006) - et al.
Anatomical and physiological plasticity of dendritic spines
Annu Rev Neurosci
(2007) - et al.
Theta-burst stimulation over primary motor cortex degrades early motor learning
Eur J Neurosci
(2010) - et al.
Rapid formation and selective stabilization of synapses for enduring motor memories
Nature
(2009) - et al.
Transient and persistent dendritic spines in the neocortex in vivo
Neuron
(2005) - et al.
Stably maintained dendritic spines are associated with lifelong memories
Nature
(2009) - et al.
Dendritic spine abnormalities in amyloid precursor protein transgenic mice demonstrated by gene transfer and intravital multiphoton microscopy
J Neurosci
(2005) - et al.
Functional clustering of neurons in motor cortex determined by cellular resolution imaging in awake behaving mice
J Neurosci
(2009) - et al.
Cortical synaptogenesis and motor map reorganization occur during late, but not early, phase of motor skill learning
J Neurosci
(2004)
Use-dependent alterations of movement representations in primary motor cortex of adult squirrel monkeys
J Neurosci
Differential modulation of motor cortical plasticity and excitability in early and late phases of human motor learning
J Neurosci
Plasticity during stroke recovery: from synapse to behaviour
Nat Rev Neurosci
Rewiring of hindlimb corticospinal neurons after spinal cord injury
Nat Neurosci
Massive restructuring of neuronal circuits during functional reorganization of adult visual cortex
Nat Neurosci
Structure and function of dendritic spines
Annu Rev Physiol
Dendritic spines and long-term plasticity
Nat Rev Neurosci
Dendritic spine plasticity: looking beyond development
Brain Res
Experience-dependent structural synaptic plasticity in the mammalian brain
Nat Rev Neurosci
Dendritic spine dynamics
Annu Rev Physiol
Transient spine expansion and learning-induced plasticity in layer 1 primary motor cortex
J Neurosci
Learning-induced LTP in neocortex
Science
Learning modifies subsequent induction of long-term potentiation-like and long-term depression-like plasticity in human motor cortex
J Neurosci
Plasticity of the synaptic modification range
J Neurophysiol
Training-induced and electrically induced potentiation in the neocortex
Neurobiol Learn Mem
Homeostatic and nonhomeostatic modulation of learning in human motor cortex
J Neurosci
Long-term potentiation induces expanded movement representations and dendritic hypertrophy in layer V of rat sensorimotor neocortex
Cereb Cortex
Cited by (88)
MARK1 regulates dendritic spine morphogenesis and cognitive functions in vivo
2024, Experimental NeurologyUnderstanding the physical basis of memory: Molecular mechanisms of the engram
2022, Journal of Biological ChemistryCitation Excerpt :Their remodeling, determined by the actin cytoskeleton (194), contributes to both modifying synaptic weight and synaptic wiring or connectivity. Dendritic turnover, although higher during development, also happens in adult brains (200–202). Rapidly formed after an experience, they have been suggested to act as a lasting structural ground for memory storage (203–205).
The Primary Motor Cortex: The Hub of Motor Learning in Rodents
2022, NeuroscienceCitation Excerpt :Motor skill learning is the capability of an organism to adjust its motion to changing surroundings. The primary motor cortex (M1) has been mainly focused upon as the central hub responsible for overall motor decisions and movements (Yu and Zuo, 2011; Hooks et al., 2013; Bhattacharjee et al., 2021). Various studies have elucidated significant morphological or functional alterations in the brain associated with motor learning.
Post-learning micro- and macro-structural neuroplasticity changes with time and sleep
2021, Biochemical PharmacologyCortical Synaptic AMPA Receptor Plasticity during Motor Learning
2020, NeuronCitation Excerpt :The primary motor cortex has been identified as one of the primary sites of neuronal and synaptic plasticity during motor learning. Changes in synaptic strength, spine dynamics, and neuronal firing patterns as well as the necessity of this part of the brain for task execution have been demonstrated during different forms of skilled motor learning in rodents (Peters et al., 2017b; Sanes and Donoghue, 2000; Yu and Zuo, 2011). Interestingly, most studies show that motor-learning-related plasticity is limited to the motor cortex contralateral to the trained paw (Rioult-Pedotti et al., 1998; Xu et al., 2009).