AMPA-silent synapses in brain development and pathology

Hanse, Eric; Seth, Henrik; Riebe, Ilse

doi:10.1038/nrn3642

Cited by 152 publications

(163 citation statements)

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“…Silent synapses are a characteristic feature of immature neuronal circuits in various areas of the brain (Kerchner and Nicoll, 2008;Hanse et al, 2013). Trafficking of AMPA receptors is critical for postsynaptic unsilencing, however, less is known about the relative contribution of various endogenously expressed AMPAR subunits to this process.…”

Section: Physiological Significance Of Glua4-dependent Plasticity In mentioning

confidence: 99%

“…Silent synapse activation is thought to be critical for strengthening of AMPA transmission during development (Kerchner and Nicoll, 2008;Hanse et al, 2013). In support of a possible role of GluA4-dependent plasticity in silent synapse activation, the relative strength of AMPAR-mediated transmission (AMPA/NMDA ratio) was lower in GluA4-/-mice as compared to WTs during the second and third week of postnatal development (P6-P18), corresponding to the period of intense AMPAfication of transmission at WT CA3-CA1 synapses.…”

Section: Physiological Significance Of Glua4-dependent Plasticity In mentioning

confidence: 99%

“…Premature, or delayed, unsilencing of AMPAR-silent synapses has been implicated in various neurodevelopmental disorders (Hanse et al, 2013). Interestingly, GluA4 -/-mice exhibit some aspects of schizophrenia-related phenotypes (Sagata et al, 2010).…”

Section: Physiological Significance Of Glua4-dependent Plasticity In mentioning

confidence: 99%

“…This involves strengthening and stabilization of immature synapses via both presynaptic and postsynaptic mechanisms. The regulated insertion of AMPA receptors to weak or functionally silent synapses is thought to be a key postsynaptic mechanism underlying experiencedependent maturation of transmission (Kerchner and Nicoll 2008;Hanse et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

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Molecular mechanisms controlling synaptic recruitment of GluA4 subunit-containing AMPA-receptors critical for functional maturation of CA1 glutamatergic synapses

et al. 2017

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Synaptic recruitment of AMPA receptors (AMPARs) represents a key postsynaptic mechanism driving functional development and maturation of glutamatergic synapses. At immature hippocampal synapses, PKA-driven synaptic insertion of GluA4 is the predominant mechanism for synaptic reinforcement. However, the physiological significance and molecular determinants of this developmentally restricted form of plasticity are not known. Here we show that PKA activation leads to insertion of GluA4 to synaptic sites with initially weak or silent AMPAR-mediated transmission. This effect depends on a novel mechanism involving the extreme C-terminal end of GluA4, which interacts with the membrane proximal region of the C-terminal domain to control GluA4 trafficking. In the absence of GluA4, strengthening of AMPAR-mediated transmission during postnatal development was significantly delayed. These data suggest that the GluA4-mediated activation of silent synapses is a critical mechanism facilitating the functional maturation of glutamatergic circuitry during the critical period of experience-dependent fine-tuning.

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Section: Physiological Significance Of Glua4-dependent Plasticity In mentioning

confidence: 99%

Section: Physiological Significance Of Glua4-dependent Plasticity In mentioning

confidence: 99%

Section: Physiological Significance Of Glua4-dependent Plasticity In mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Molecular mechanisms controlling synaptic recruitment of GluA4 subunit-containing AMPA-receptors critical for functional maturation of CA1 glutamatergic synapses

et al. 2017

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“…Lower AMPAR/NMDAR current ratio together with higher amplitude and slower decay of NMDAR current predict presence of silent synapses, which have NMDAR but lack functional AMPAR (Hanse et al, 2013). Silent synapses were examined using the CV analysis and comparison of failures of NMDAR-and AMPAR-mediated EPSCs evoked by weak stimulation (Kullmann, 1994;Marie et al, 2005;Pan et al, 2009).…”

Section: Of Generates Silent Synapses In Dmpfc Input To Blamentioning

confidence: 99%

Observation of Distressed Conspecific as a Model of Emotional Trauma Generates Silent Synapses in the Prefrontal-Amygdala Pathway and Enhances Fear Learning, but Ketamine Abolishes those Effects

Ito

Erişir

Morozov

2015

Neuropsychopharmacol

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Witnessing pain and distress in others can cause psychological trauma and increase odds of developing PTSD in the future, on exposure to another stressful event. However, the underlying synaptic process remains unknown. Here we report that mice exposed to a conspecific receiving electrical footshocks exhibited enhanced passive avoidance (PA) learning when trained 24 h after the exposure. The exposure activated neurons in the dorsomedial prefrontal cortex (dmPFC) and basolateral amygdala (BLA) and altered synaptic transmission from dmPFC to BLA. It increased amplitude, slowed decay of NMDA receptor-mediated currents, and generated silent synapses. Administration of sub-anesthetic ketamine immediately after the exposure prevented the enhancement of PA learning and silent synapse formation. These findings suggest that ketamine can prevent pathophysiological consequences of psychological trauma.

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Activity‐Dependent Induction of Younger Biological Phenotypes

Lissek

2022

Advanced Biology

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In several mammalian species, including humans, complex stimulation patterns such as cognitive and physical exercise lead to improvements in organ function, organism health and performance, as well as possibly longer lifespans. A framework is introduced here in which activity‐dependent transcriptional programs, induced by these environmental stimuli, move somatic cells such as neurons and muscle cells toward a state that resembles younger cells to allow remodeling and adaptation of the organism. This cellular adaptation program targets several process classes that are heavily implicated in aging, such as mitochondrial metabolism, cell–cell communication, and epigenetic information processing, and leads to functional improvements in these areas. The activity‐dependent gene program (ADGP) can be seen as a natural, endogenous cellular reprogramming mechanism that provides deep insight into the principles of inducible improvements in cell and organism function and can guide the development of therapeutic approaches for longevity. Here, these ADGPs are analyzed, exemplary critical molecular nexus points such as cAMP response element‐binding protein, myocyte enhancer factor 2, serum response factor, and c‐Fos are identified, and it is explored how one may leverage them to prevent, attenuate, and reverse human aging‐related decline of body function.

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AMPA-silent synapses in brain development and pathology

Cited by 152 publications

References 189 publications

Molecular mechanisms controlling synaptic recruitment of GluA4 subunit-containing AMPA-receptors critical for functional maturation of CA1 glutamatergic synapses

Molecular mechanisms controlling synaptic recruitment of GluA4 subunit-containing AMPA-receptors critical for functional maturation of CA1 glutamatergic synapses

Observation of Distressed Conspecific as a Model of Emotional Trauma Generates Silent Synapses in the Prefrontal-Amygdala Pathway and Enhances Fear Learning, but Ketamine Abolishes those Effects

Activity‐Dependent Induction of Younger Biological Phenotypes

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