Conversion of short-term potentiation to long-term potentiation in mouse CA1 by coactivation of β-adrenergic and muscarinic receptors.
Encoding new information requires dynamic changes in synaptic strength. The brain can boost synaptic plasticity through the secretion of neuromodulatory substances, including acetylcholine and noradrenaline. Considerable effort has focused on elucidating how neuromodulatory substances alter synaptic properties. However, determination of the potential synergistic interactions between different neuromodulatory systems remains incomplete. Previous results indicate that coactivation of β-adrenergic and cholinergic receptors facilitated the conversion of STP to LTP through an extracellular signal-regulated kinase (ERK)-dependent mechanism. ERK signaling has been linked to synaptically localized translation regulation. Thus, we hypothesized that costimulation of noradrenergic and cholinergic receptors could initiate the transformation of STP to LTP through up-regulation of protein synthesis. Our results indicate that a protocol which yields STP (5 Hz, 5 sec) when paired with coapplication of the β-adrenergic agonist, isoproterenol (ISO), and the cholinergic agonist, carbachol (CCh), induces translation-dependent LTP in mouse CA1. This form of LTP requires both β1-adrenergic and M1 muscarinic receptor activation, as blocking either receptor subtype prevented LTP induction. Blocking ERK, mTOR, or translation reduced the expression of LTP induced with ISO + CCh. Taken together, our data demonstrate that coactivation of β-adrenergic and muscarinic receptors facilitates the conversion of STP to LTP through a mechanism requiring translation initiation.
Centre for Neuroscience, University of Alberta School of Medicine, Edmonton, Alberta, T6G 2H7, Canada.
Steven A
SA
Connor
Sabyasachi
S
Maity
Birbickram
B
Roy
Declan W
DW
Ali
Peter V
PV
Nguyen
D000818:Animals; D056547:CA1 Region, Hippocampal / Q000502:physiology*; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D017774:Long-Term Potentiation / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018408:Patch-Clamp Techniques; D014176:Protein Biosynthesis; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D011976:Receptors, Muscarinic / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*
D011943:Receptors, Adrenergic, beta; D011976:Receptors, Muscarinic