Rapid Target-Specific Remodeling of Fast-Spiking Inhibitory Circuits after Loss of Dopamine

Gittis, Aryn H.; Hang, Giao B.; LaDow, Eva; Shoenfeld, Liza R.; Atallah, Bassam V.; Finkbeiner, Steven; Kreitzer, Anatol C.

doi:10.1016/j.neuron.2011.06.035

Cited by 160 publications

(162 citation statements)

References 91 publications

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“…Thus, deletion of D2R in the MSNs mirrors the motor impairments observed by the total loss of D2Rs in D2R-null mice (Baik et al, 1995;Jung et al, 1999) and support the critical role of these receptors in modulating the activity of D2R-expressing MSNs of the indirect pathway (Gittis et al, 2011). D2R floxflox/En1Cre/ϩ mice, however, are hyperactive when exposed to a novel environment, in particular during the early phase of exploration, and hyperresponsive to DAT blockade by cocaine.…”

Section: Discussionsupporting

confidence: 57%

Dual Control of Dopamine Synthesis and Release by Presynaptic and Postsynaptic Dopamine D2 Receptors

Anzalone

Lizardi-Ortiz²,

Ramos³

et al. 2012

Journal of Neuroscience

172

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Dysfunctions of dopaminergic homeostasis leading to either low or high dopamine (DA) levels are causally linked to Parkinson's disease, schizophrenia, and addiction. Major sites of DA synthesis are the mesencephalic neurons originating in the substantia nigra and ventral tegmental area; these structures send major projections to the dorsal striatum (DSt) and nucleus accumbens (NAcc), respectively. DA finely tunes its own synthesis and release by activating DA D2 receptors (D2R). To date, this critical D2R-dependent function was thought to be solely due to activation of D2Rs on dopaminergic neurons (D2 autoreceptors); instead, using site-specific D2R knock-out mice, we uncover that D2 heteroreceptors located on non-DAergic medium spiny neurons participate in the control of DA levels. This D2 heteroreceptor-mediated mechanism is more efficient in the DSt than in NAcc, indicating that D2R signaling differentially regulates mesolimbic-versus nigrostriatal-mediated functions. This study reveals previously unappreciated control of DA signaling, shedding new light on region-specific regulation of DA-mediated effects.

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Section: Discussionsupporting

confidence: 57%

Dual Control of Dopamine Synthesis and Release by Presynaptic and Postsynaptic Dopamine D2 Receptors

Anzalone

Lizardi-Ortiz²,

Ramos³

et al. 2012

Journal of Neuroscience

172

View full text Add to dashboard Cite

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“…Experiments in mice have revealed that chronic dopamine depletion increases the functional connectivity between striatal fast-spiking interneurons and the group of medium spiny neurons (MSNs) that project to the external segment of the globus pallidus (GPe), a part of the indirect basal ganglia pathway. These changes were shown to be sufficient to increase the synchrony between the GPe-projecting MSNs in a computer model of the striatal network incorporating interneurons and MSNs (Gittis et al, 2011). Similar findings have been made using acute pharmacological manipulations of cholinergic striatal interneurons leading to the induction of striatal beta oscillations (McCarthy et al, 2011).…”

Section: Oscillations In Corticobasal Ganglia Circuitssupporting

confidence: 62%

Mechanisms underlying cortical resonant states: implications for levodopa-induced dyskinesia

Richter

Halje

Petersson

2013

Reviews in the Neurosciences

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A common observation in recordings of neuronal activity from the cerebral cortex is that populations of neurons show patterns of synchronized oscillatory activity. However, it has been suggested that neuronal synchronization can, in certain pathological conditions, become excessive and possibly have a pathogenic role. In particular, aberrant oscillatory activation patterns have been implicated in conditions involving cortical dysfunction. We here review the mechanisms thought to be involved in the generation of cortical oscillations and discuss their relevance in relation to a recent finding indicating that high-frequency oscillations in the cerebral cortex have an important role in the generation of levodopa-induced dyskinesia. On the basis of these insights, it is suggested that the identification of physiological changes associated with symptoms of disease is a particularly important first step toward a more rapid development of novel treatment strategies.

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“…Changes in structural plasticity were detected within hours following peripheral lesions, suggesting that they might account for rapid changes in functional plasticity of receptive fields. Furthermore, dramatic changes in structural plasticity by fast-spiking striatal inhibitory neuron axons that specifically target the indirect striatal pathway were detected following lesions that result in dopamine deprivation 97 . Finally, two recent studies in sensory-deprived visual cortex provided evidence that regulation of structural plasticity by inhibitory interneurons may provide permissive conditions for subsequent plasticity by excitatory neurons.…”

Section: Inhibitory Circuit Rearrangementsmentioning

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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Rapid Target-Specific Remodeling of Fast-Spiking Inhibitory Circuits after Loss of Dopamine

Cited by 160 publications

References 91 publications

Dual Control of Dopamine Synthesis and Release by Presynaptic and Postsynaptic Dopamine D2 Receptors

Dual Control of Dopamine Synthesis and Release by Presynaptic and Postsynaptic Dopamine D2 Receptors

Mechanisms underlying cortical resonant states: implications for levodopa-induced dyskinesia

Structural plasticity upon learning: regulation and functions

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