Activity-regulated genes as mediators of neural circuit plasticity

Leslie, Jennifer H.; Nedivi, Elly

doi:10.1016/j.pneurobio.2011.05.002

Cited by 108 publications

(93 citation statements)

References 262 publications

(387 reference statements)

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“…18,19 Psychostimulant-regulated immediate-early genes (IEGs) include both transcription factors of the Fos/Jun/Egr families as well neuronally-enriched genes such as Arc, Bdnf and Cdk5 that play direct roles in the plasticity of synaptic strength and structure. [19][20][21][22] We have shown that amphetamine increases expression of Fos/ Jun family transcription factors in the striatum of both WT and MUT mice of the Mecp2 308 strain, demonstrating that expression of wild-type MeCP2 is not required for the IEG response. 7 However, both the magnitude of FosB and JunB induction following a single dose of amphetamine and the plasticity of Fos, FosB and JunB inducibility following repeated amphetamine is significantly altered in Mecp2 MUT mice.…”

Section: Mutation Of Mecp2 Alters Transcriptional Regulation Of Selecmentioning

confidence: 91%

Mutation of MeCP2 alters transcriptional regulation of select immediate-early genes

May

West

2012

Epigenetics

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Section: Mutation Of Mecp2 Alters Transcriptional Regulation Of Selecmentioning

confidence: 91%

Mutation of MeCP2 alters transcriptional regulation of select immediate-early genes

May

West

2012

Epigenetics

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“…4. In most cases, plasticity regulation involves signalling pathways relating neuronal activity to the expression of key activity-regulated genes [71][72][73] . Consistent with its central roles in mediating signalling downstream of synaptic activity, calcium has prominent roles in activity-regulated gene expression.…”

Section: Plasticity Regulationmentioning

confidence: 99%

Structural plasticity upon learning: regulation and functions

2012

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The contributions of brain networks to information processing and learning and memory are classically interpreted within the framework of Hebbian plasticity and the notion that synaptic weights can be modified by specific patterns of activity. However, accumulating evidence over the past decade indicates that synaptic networks are also structurally plastic, and that connectivity is remodelled throughout life, through mechanisms of synapse formation, stabilization and elimination 1. This has led to the concept of structural plasticity, which can encompass a variety of morphological changes that have functional consequences. These include on the one hand structural rearrangements at pre-existing synapses, and on the other hand the formation or loss of synapses, of neuronal processes that form synapses or of neurons. In this Review we focus on plasticity that involves gains and/or losses of synapses. Its key potential implication for learning and memory is to physically alter circuit connectivity, thus providing long-lasting memory traces that can be recruited at subsequent retrieval. Detecting this form of plasticity and relating it to its possible functions poses unique challenges, which are in part due to our still limited understanding of how structure relates to function in the nervous system.We review recent studies that relate the structural plasticity of neuronal circuits to behavioural learning and memory and discuss conceptual and mechanistic advances, as well as future challenges. The studies establish a number of strong links between specific behavioural learning processes and the assembly and loss of specific synapses. Further areas of substantial progress include molecular and cellular mechanisms that regulate synapse dynamics in response to alterations in synaptic activity, the specific spatial distribution of the syn aptic changes among identified neurons and dendrites and the relative roles of excitation and inhibition in regulating structural plasticity.The new findings provide exciting early vistas of how learning and memory may be implemented at the level of structural circuit plasticity. At the same time, they highlight major gaps in our understanding of plasticity regulation at the cellular, circuit and systems levels. Accordingly, achieving a better mechanistic understanding of learning and memory processes is likely to depend on the development of more effective techniques and models to investigate ensembles of identified synapses longitudinally, both functionally and structurally. Molecular mechanisms of synapse remodellingA remarkable feature of excitatory and inhibitory synapses is their high level of structural variability 2 and the fact that their morphologies and stabilities change over time 3 . This phenomenon is regulated by activity, and the size of spine heads correlates with synaptic strength 4 , presynaptic properties 5 and the long-term stability of the synapse 6 . The morphological characteristics of synapses thus reveal important features of their function and stabilit...

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“…This heterogeneity poses major challenges to the study of neural coding in general and neural plasticity in particular. In the context of plasticity, one way to deal with such heterogeneity is to study the same neurons repeatedly, an approach that has proven highly useful in anatomical studies (8,10,(25)(26)(27)(28)(29)(30)(31). Thus, we devised a way to study the physiology of single cells over long time scales.…”

Section: Resultsmentioning

confidence: 99%

Time-lapse electrical recordings of single neurons from the mouse neocortex

Cohen

Koffman

Meiri

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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The ability of the brain to adapt to environmental demands implies that neurons can change throughout life. The extent to which single neurons actually change remains largely unstudied, however. To evaluate how functional properties of single neurons change over time, we devised a way to perform in vivo time-lapse electrophysiological recordings from the exact same neuron. We monitored the contralateral and ipsilateral sensory-evoked spiking activity of individual L2/3 neurons from the somatosensory cortex of mice. At the end of the first recording session, we electroporated the neuron with a DNA plasmid to drive GFP expression. Then, 2 wk later, we visually guided a recording electrode in vivo to the GFP-expressing neuron for the second time. We found that contralateral and ipsilateral evoked responses (i.e., probability to respond, latency, and preference), and spontaneous activity of individual L2/3 pyramidal neurons are stable under control conditions, but that this stability could be rapidly disrupted. Contralateral whisker deprivation induced robust changes in sensoryevoked response profiles of single neurons. Our experiments provide a framework for studying the stability and plasticity of single neurons over long time scales using electrophysiology.electroporation | two-photon imaging I t is well established that the morphology and response properties of neurons are highly dynamic during development. Immature cortical neurons are particularly amenable to change during specific stages of development, when spontaneous activity and sensory experience shape their morphology and physiology (1-4). Once formed and stabilized, neurons are thought to maintain some aspects of this plasticity during adulthood, albeit at a lower level (5-7); however, the extent to which single-neuron physiology changes or remains stable in the adult mammalian brain is poorly documented.Limitations to the study of single-neuron plasticity stem from technical difficulties as well as from the inherent heterogeneity of single neurons in a circuit. Fine changes, like those that underlie functional plasticity, can go undetected due to data averaging and homeostatic events that may cancel out each other. As a result, plasticity is made experimentally more tractable by studying populations after gross manipulations like sensory deprivation or injury. For example, receptive fields of neurons across adult rodent cortices are known to shift in response to different paradigms of sensory input manipulation (8-14). Whether and how other forms of plasticity, such as learning and memory, mark their signature on single neurons is more difficult to deduce from gross manipulation studies. One way to overcome some of these difficulties is through experiments based on time-lapse imaging and electrophysiology (14-18). However, the ability to measure fine temporal physiological events of identifiable single neurons over long time scales remains limited, especially with electrophysiology.To establish a method to follow the electrophysiology of single neuron...

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Activity-regulated genes as mediators of neural circuit plasticity

Cited by 108 publications

References 262 publications

Mutation of MeCP2 alters transcriptional regulation of select immediate-early genes

Mutation of MeCP2 alters transcriptional regulation of select immediate-early genes

Structural plasticity upon learning: regulation and functions

Time-lapse electrical recordings of single neurons from the mouse neocortex

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