Abstract
Activity-dependent local protein synthesis is critical for synapse-specific, persistent plasticity. Abnormalities in local protein synthesis have been implicated in psychiatric disorders. We have recently identified the translin/trax microRNA-degrading enzyme as a novel mediator of protein synthesis at activated synapses. Additionally, mice lacking translin/trax exhibit some of the behavioral abnormalities found in a mouse model of fragile X syndrome. Therefore, identifying signaling pathways interacting with translin/trax to support persistent synaptic plasticity is a translationally relevant goal. Here, as a first step to achieve this goal, we have assessed the requirement of translin/trax for multiple hippocampal synaptic plasticity paradigms that rely on distinct molecular mechanisms. We found that mice lacking translin/trax exhibited selective impairment in a form of persistent hippocampal plasticity, which requires postsynaptic PKA activity. In contrast, enduring forms of plasticity that are dependent on presynaptic PKA were unaffected. Furthermore, these mice did not display exaggerated metabotropic glutamate receptor-mediated long-term synaptic depression, a hallmark of the mouse model of fragile X syndrome. Taken together, these findings demonstrate that translin/trax mediates long-term synaptic plasticity that is dependent on postsynaptic PKA signaling.
Competing Interest Statement
The authors have declared no competing interest.
List of abbreviations
- aCSF
- artificial cerebrospinal fluid
- AC
- adenylyl cyclase
- ACVR1C
- activin receptor type 1-C
- AMPAR
- α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor
- CaM
- calmodulin
- cAMP
- cyclic adenosine monophosphate
- DHPG
- (RS)-3,5-Dihydroxyphenylglycine
- fEPSP
- field excitatory postsynaptic potential
- FMRP
- fragile X mental retardation protein
- FSK
- forskolin
- GPCR
- G-protein coupled receptor
- LTP
- long-term potentiation
- LTD
- long-term depression
- mGluR
- metabotropic glutamate receptor
- miRISC
- microRNA-induced silencing complex
- NMDAR
- N-methyl D-aspartate receptor
- PDE
- phosphodiesterase
- PKA
- protein kinase A
- RBP
- RNA-binding protein
- RNase
- ribonuclease
- TBS
- theta-burst stimulation
- TN/TX
- translin/trax
- Trax
- translin-associated protein-X