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Neuroscience: CNS disease, pain, brain research, ion channels, synaptic transmission, channelopathies, neuronal network
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Inhibitory Plasticity Dictates the Sign of Plasticity at Excitatory Synapses

The broad connectivity of inhibitory interneurons and the capacity of inhibitory synapses to be plastic make them ideal regulators of the level of excitability of many neurons simultaneously. Whether inhibitory synaptic plasticity may also contribute to the selective regulation of single neurons and local microcircuits activity has not been investigated. Here we demonstrate that in rat primary visual cortex inhibitory synaptic plasticity is connection specific and depends on the activation of postsynaptic GABAB–Gi/o protein signaling. Through the activation of this intracellular signaling pathway, inhibitory plasticity can alter the state of a single postsynaptic neuron and directly affect the induction of plasticity at its glutamatergic inputs. This interaction is modulated by sensory experience. Our data demonstrate that in recurrent circuits, excitatory and inhibitory forms of synaptic plasticity are not integrated as independent events, but interact to cooperatively drive the activity-dependent rewiring of local microcircuits. (...) - by Wang L and Maffei A, The Journal of Neuroscience, 22 January 2014, 34(4): 1083-1093

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Age-Dependent MicroRNA Control of Synaptic Plasticity in 22q11 Deletion Syndrome and Schizophrenia

Age-Dependent MicroRNA Control of Synaptic Plasticity in 22q11 Deletion Syndrome and Schizophrenia | Neuroscience_topics | Scoop.it

The 22q11 deletion syndrome (22q11DS) is characterized by multiple physical and psychiatric abnormalities and is caused by the hemizygous deletion of a 1.5–3 Mb region of chromosome 22. It constitutes one of the strongest known genetic risks for schizophrenia; schizophrenia arises in as many as 30% of patients with 22q11DS during adolescence or early adulthood. A mouse model of 22q11DS displays an age-dependent increase in hippocampal long-term potentiation (LTP), a form of synaptic plasticity underlying learning and memory. The sarco(endo)plasmic reticulum Ca2+ ATPase (SERCA2), which is responsible for loading Ca2+ into the endoplasmic reticulum (ER), is elevated in this mouse model. The resulting increase in ER Ca2+ load leads to enhanced neurotransmitter release and increased LTP. However, the mechanism by which the 22q11 microdeletion leads to SERCA2 overexpression and LTP increase has not been determined. Screening of multiple mutant mouse lines revealed that haploinsufficiency of Dgcr8, a microRNA (miRNA) biogenesis gene in the 22q11DS disease-critical region, causes age-dependent, synaptic SERCA2 overexpression and increased LTP. We found that miR-25 and miR-185, regulators of SERCA2, are depleted in mouse models of 22q11DS. Restoration of these miRNAs to presynaptic neurons rescues LTP in Dgcr8+/− mice. Finally, we show that SERCA2 is elevated in the brains of patients with schizophrenia, providing a link between mouse model findings and the human disease. We conclude that miRNA-dependent SERCA2 dysregulation is a pathogenic event in 22q11DS and schizophrenia. - by Earls LR et al., The Journal of Neuroscience, 10 October 2012, 32(41): 14132-14144

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Metabotropic NMDA receptor function is required for NMDA receptor-dependent long-term depression

NMDA receptor (NMDAR) activation controls long-term potentiation (LTP) as well as long-term depression (LTD) of synaptic transmission, cellular models of learning and memory. A long-standing view proposes that a high level of Ca2+ entry through NMDARs triggers LTP; lower Ca2+ entry triggers LTD. Here we show that ligand binding to NMDARs is sufficient to induce LTD; neither ion flow through NMDARs nor Ca2+ rise is required. However, basal levels of Ca2+ are permissively required. Lowering, but not maintaining, basal Ca2+levels with Ca2+ chelators blocks LTD and drives strong synaptic potentiation, indicating that basal Ca2+levels control NMDAR-dependent LTD and basal synaptic transmission. Our findings indicate that metabotropic actions of NMDARs can weaken active synapses without raising postsynaptic calcium, thereby revising and expanding the mechanisms controlling synaptic plasticity. (...) - by Nabavi S. et al.PNAS 2013 110 (10) 4027-4032

Julien Hering, PhD's insight:

A great article from R. Malinov's team about fine mechanisms controlling synaptic plasticity through levels of calcium 

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Sleep Oscillations in the Thalamocortical System Induce Long-Term Neuronal Plasticity

Sleep Oscillations in the Thalamocortical System Induce Long-Term Neuronal Plasticity | Neuroscience_topics | Scoop.it

Highlights

  • Slow-wave sleep induces long-term potentiation of evoked responses
  • In vitro, stimulation mimicking SWS replicated these results
  • Potentiation of responses was postsynaptic, Ca2+, AMPA, and NMDA dependent
  • The mechanism of potentiation was compatible with the classical LTP mechanism

Summary

Long-term plasticity contributes to memory formation and sleep plays a critical role in memory consolidation. However, it is unclear whether sleep slow oscillation by itself induces long-term plasticity that contributes to memory retention. Using in vivo prethalamic electrical stimulation at 1 Hz, which itself does not induce immediate potentiation of evoked responses, we investigated how the cortical evoked response was modulated by different states of vigilance. We found that somatosensory evoked potentials during wake were enhanced after a slow-wave sleep episode (with or without stimulation during sleep) as compared to a previous wake episode. In vitro, we determined that this enhancement has a postsynaptic mechanism that is calcium dependent, requires hyperpolarization periods (slow waves), and requires a coactivation of both AMPA and NMDA receptors. Our results suggest that long-term potentiation occurs during slow-wave sleep, supporting its contribution to memory.

Sylvain Chauvette, Josée Seigneur, Igor TimofeevNeuron, Volume 75, Issue 6, 1105-1113, 20 September 2012

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