MuSK expressed in the brain mediates cholinergic responses, synaptic plasticity, and memory formation.
Muscle-specific tyrosine kinase receptor (MuSK) has been believed to be mainly expressed and functional in muscle, in which it mediates the formation of neuromuscular junctions. Here we show that MuSK is expressed in the brain, particularly in neurons, as well as in non-neuronal tissues. We also provide evidence that MuSK expression in the hippocampus is required for memory consolidation, because temporally restricted knockdown after training impairs memory retention. Hippocampal disruption of MuSK also prevents the learning-dependent induction of both cAMP response element binding protein (CREB) phosphorylation and CCAAT enhancer binding protein beta (C/EBPbeta) expression, suggesting that the role of MuSK during memory consolidation critically involves the CREB-C/EBP pathway. Furthermore, we found that MuSK also plays an important role in mediating hippocampal oscillatory activity in the theta frequency as well as in the induction and maintenance of long-term potentiation, two synaptic responses that correlate with memory formation. We conclude that MuSK plays an important role in brain functions, including memory formation. Therefore, its expression and role are broader than what was believed previously.
Garcia-Osta
Ana
A
Department of Neuroscience, Mount Sinai School of Medicine, New York, New York 10029, USA.
Tsokas
Panayiotis
P
Pollonini
Gabriella
G
Landau
Emmanuel M
EM
Blitzer
Robert
R
Alberini
Cristina M
CM
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D006624:Hippocampus / Q000502:physiology*; D017774:Long-Term Potentiation / Q000502:physiology; D008297:Male; D008568:Memory / Q000502:physiology*; D009473:Neuronal Plasticity / Q000502:physiology*; D051381:Rats; D020318:Rats, Long-Evans; D020794:Receptor Protein-Tyrosine Kinases; D011950:Receptors, Cholinergic; D013569:Synapses / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology*; D014018:Tissue Distribution
D011950:Receptors, Cholinergic; C475048:MuSK protein, rat; D020794:Receptor Protein-Tyrosine Kinases; D000109:Acetylcholine