Membrane-tethered AKT kinase regulates basal synaptic transmission and early phase LTP expression by modulation of post-synaptic AMPA receptor level

• Published in: Hippocampus 2016-09, Vol.26 (9), p.1149-1167
• Main Authors: Pen, Y., Borovok, N., Reichenstein, M., Sheinin, A., Michaelevski, I.
• Format: Article
• Language: English
• Subjects: AKT kinase; AMPA receptors; Animals; Cell Membrane - drug effects; Cell Membrane - metabolism; Cells, Cultured; Cerebral Cortex - drug effects; Cerebral Cortex - metabolism; Hippocampus - drug effects; Hippocampus - metabolism; Long-Term Potentiation - drug effects; Long-Term Potentiation - physiology; LTP; Male; Patch-Clamp Techniques; Proto-Oncogene Proteins c-akt - antagonists & inhibitors; Proto-Oncogene Proteins c-akt - metabolism; Rats, Sprague-Dawley; Receptors, AMPA - metabolism; Synapses - drug effects; Synapses - metabolism; synaptic plasticity; synaptic transmission; Synaptic Transmission - drug effects; Synaptic Transmission - physiology; Tissue Culture Techniques
• ISSN: 1050-9631; 1098-1063
• DOI: 10.1002/hipo.22597

ABSTRACT The serine/threonine kinase AKT/PKB plays a fundamental role in a wide variety of neuronal functions, including neuronal cell development, axonal growth, and synaptic plasticity. Multiple evidence link AKT signaling pathways to regulation of late phase long‐term synaptic plasticity, synaptogenesis, and spinogenesis, as well as long‐term memory formation. Nevertheless, the downstream effectors mediating the effects of AKT on early phase long‐term potentiation (eLTP) are currently unknown. Here we report that using different regimes of pharmacological activation and inhibition of AKT activity in acute hippocampal slices, we found that AKT regulates the post‐synaptic expression of α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid receptor (AMPA) receptors affecting solely the expression of eLTP, with no effect on its induction and maintenance. We further show that both maintenance of basal synaptic activity and expression of eLTP require plasma membrane tethering by activated AKT and that basal synaptic activity may be regulated via the direct effects of AKT1 on the expression level of post‐synaptic AMPA receptors bypassing the canonical AKT signaling. Finally, we establish that eLTP expression requires the involvement of both the canonical AKT signaling pathways and the direct effect of AKT1 on AMPA receptor activity/expression in the post‐synaptic membrane. © 2016 Wiley Periodicals, Inc.