miR-132 couples the circadian clock to daily rhythms of neuronal plasticity and cognition
| Autor: | Kari R. Hoyt, Anisha Kalidindi, Ashley Garcia, Kelin L. Wheaton, Sydney Aten, Karl Obrietan, Kaitlin H. Snider, Diego Alzate-Correa, Katelin F. Hansen |
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| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine Methyl-CpG-Binding Protein 2 Cognitive Neuroscience Conditioning Classical Circadian clock Regulator Hippocampus Biology 03 medical and health sciences Cellular and Molecular Neuroscience miR-132 Cognition 0302 clinical medicine Sirtuin 1 Circadian Clocks Neuroplasticity Animals Circadian rhythm Mice Knockout Neurons Neuronal Plasticity Research Fear Circadian Rhythm Mice Inbred C57BL MicroRNAs 030104 developmental biology Neuropsychology and Physiological Psychology Mental Recall Knockout mouse Forebrain Female Neuroscience 030217 neurology & neurosurgery |
| Zdroj: | Learning & Memory. 25:214-229 |
| ISSN: | 1549-5485 |
| DOI: | 10.1101/lm.047191.117 |
| Popis: | The microRNA miR-132 serves as a key regulator of a wide range of plasticity-associated processes in the central nervous system. Interestingly, miR-132 expression has also been shown to be under the control of the circadian timing system. This finding, coupled with work showing that miR-132 is expressed in the hippocampus, where it influences neuronal morphology and memory, led us to test the idea that daily rhythms in miR-132 within the forebrain modulate cognition as a function of circadian time. Here, we show that hippocampal miR-132 expression is gated by the time-of-day, with peak levels occurring during the circadian night. Further, in miR-132 knockout mice and in transgenic mice, where miR-132 is constitutively expressed under the control of the tetracycline regulator system, we found that time-of-day dependent memory recall (as assessed via novel object location and contextual fear conditioning paradigms) was suppressed. Given that miRNAs exert their functional effects via the suppression of target gene expression, we examined the effects that transgenic miR-132 manipulations have on MeCP2 and Sirt1—two miR-132 targets that are associated with neuronal plasticity and cognition. In mice where miR-132 was either knocked out, or transgenically expressed, rhythmic expression of MeCP2 and Sirt1 was suppressed. Taken together, these results raise the prospect that miR-132 serves as a key route through which the circadian timing system imparts a daily rhythm on cognitive capacity. |
| Databáze: | OpenAIRE |
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