A circadian clock in hippocampus is regulated by interaction between oligophrenin-1 and Rev-erbα

Valnegri, Pamela; Khelfaoui, Malik; Dorseuil, Olivier; Bassani, Silvia; Lagneaux, Celine; Gianfelice, Antonella; Benfante, Roberta; Chelly, Jamel; Billuart, Pierre; Sala, Carlo; Passafaro, Maria

doi:10.1038/nn.2911

Cited by 58 publications

(54 citation statements)

References 46 publications

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“…Pronounced fluctuations in hippocampal gene expression patterns, neurotransmitter release, and in hippocampal synaptic excitability occur with the circadian clock (36)(37)(38)(39)(40). Any differences in the population code for an identical environment after a time interval of 6 h might therefore reflect a circadian or ultradian modulation of activity patterns.…”

Section: Resultsmentioning

confidence: 99%

Neuronal code for extended time in the hippocampus

Mankin

Sparks

Slayyeh

et al. 2012

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

354

355

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The time when an event occurs can become part of autobiographical memories. In brain structures that support such memories, a neural code should exist that represents when or how long ago events occurred. Here we describe a neuronal coding mechanism in hippocampus that can be used to represent the recency of an experience over intervals of hours to days. When the same event is repeated after such time periods, the activity patterns of hippocampal CA1 cell populations progressively differ with increasing temporal distances. Coding for space and context is nonetheless preserved. Compared with CA1, the firing patterns of hippocampal CA3 cell populations are highly reproducible, irrespective of the time interval, and thus provide a stable memory code over time. Therefore, the neuronal activity patterns in CA1 but not CA3 include a code that can be used to distinguish between time intervals on an extended scale, consistent with behavioral studies showing that the CA1 area is selectively required for temporal coding over such periods.

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Section: Resultsmentioning

confidence: 99%

Neuronal code for extended time in the hippocampus

Mankin

Sparks

Slayyeh

et al. 2012

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

354

355

View full text Add to dashboard Cite

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“…Plasmids encoding truncated GluK2 mutants were created by mutagenizing the Myc-GluK2a(R) plasmid37 using the QuikChange mutagenesis kit (Stratagene). Samples were immunoprecipitated as described38 according to the following protocol: 500 μg of sample were pre-cleared by adding 50 μl of washed Protein A or G agarose bead slurry (catalogue number 17-5138-01 and 17-0618-01, GE Healthcare). The agarose beads were collected by pulsing 5 s in the microcentrifuge at 14,000 g and discarded.…”

Section: Methodsmentioning

confidence: 99%

“…Primary rat hippocampal neurons were prepared from embryonic day 18–19 rat brains38 and plated on poly- D -lysine (30 μg ml −1 )-coated coverslips at densities of 75,000 cells per well for immunochemistry, 300,000 cells per well for biochemistry experiments and 150,000 cells per well for electrophysiological experiments. Neurons were infected with lentivirus at Days in Vitro (DIV) 8 (ref.…”

Section: Methodsmentioning

confidence: 99%

Parkin regulates kainate receptors by interacting with the GluK2 subunit

et al. 2014

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Although loss-of-function mutations in the PARK2 gene, the gene that encodes the protein parkin, cause autosomal recessive juvenile parkinsonism, the responsible molecular mechanisms remain unclear. Evidence suggests that a loss of parkin dysregulates excitatory synapses. Here we show that parkin interacts with the kainate receptor (KAR) GluK2 subunit and regulates KAR function. Loss of parkin function in primary cultured neurons causes GluK2 protein to accumulate in the plasma membrane, potentiates KAR currents and increases KAR-dependent excitotoxicity. Expression in the mouse brain of a parkin mutant causing autosomal recessive juvenile parkinsonism results in GluK2 protein accumulation and excitotoxicity. These findings show that parkin regulates KAR function in vitro and in vivo, and suggest that KAR upregulation may have a pathogenetic role in parkin-related autosomal recessive juvenile parkinsonism.

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“…BMAL1 has been implicated in hippocampal and astrocytic function (17)(18)(19)(20). In Drosophila, deletion of the Period gene exacerbates brain pathology in neurodegeneration-prone mutants (21).…”

Section: Introductionmentioning

confidence: 99%

Circadian clock proteins regulate neuronal redox homeostasis and neurodegeneration

Musiek¹,

Lim²,

Yang³

et al. 2013

J. Clin. Invest.

423

448

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Brain aging is associated with diminished circadian clock output and decreased expression of the core clock proteins, which regulate many aspects of cellular biochemistry and metabolism. The genes encoding clock proteins are expressed throughout the brain, though it is unknown whether these proteins modulate brain homeostasis. We observed that deletion of circadian clock transcriptional activators aryl hydrocarbon receptor nuclear translocator-like (Bmal1) alone, or circadian locomotor output cycles kaput (Clock) in combination with neuronal PAS domain protein 2 (Npas2), induced severe age-dependent astrogliosis in the cortex and hippocampus. Mice lacking the clock gene repressors period circadian clock 1 (Per1) and period circadian clock 2 (Per2) had no observed astrogliosis. Bmal1 deletion caused the degeneration of synaptic terminals and impaired cortical functional connectivity, as well as neuronal oxidative damage and impaired expression of several redox defense genes. Targeted deletion of Bmal1 in neurons and glia caused similar neuropathology, despite the retention of intact circadian behavioral and sleep-wake rhythms. Reduction of Bmal1 expression promoted neuronal death in primary cultures and in mice treated with a chemical inducer of oxidative injury and striatal neurodegeneration. Our findings indicate that BMAL1 in a complex with CLOCK or NPAS2 regulates cerebral redox homeostasis and connects impaired clock gene function to neurodegeneration.

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A circadian clock in hippocampus is regulated by interaction between oligophrenin-1 and Rev-erbα

Cited by 58 publications

References 46 publications

Neuronal code for extended time in the hippocampus

Neuronal code for extended time in the hippocampus

Parkin regulates kainate receptors by interacting with the GluK2 subunit

Circadian clock proteins regulate neuronal redox homeostasis and neurodegeneration

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