Selective Phosphorylation of AMPA Receptor Contributes to the Network of Long-Term Potentiation in the Anterior Cingulate Cortex

Abstract

Phosphorylation of AMPA receptor GluA1 plays important roles in synaptic potentiation. Most previous studies have been performed in the hippocampus, while the roles of GluA1 phosphorylation in the cortex remain unknown. Here we investigated the involvement of the phosphorylation of GluA1 in the LTP in the anterior cingulate cortex (ACC) using mice with a GluA1 knock-in mutation at the PKA phosphorylation site serine 845 (s845A) or CaMKII/PKC phosphorylation site serine 831 (s831A). The network LTP, which is constructed by multiple recordings of LTP at different locations within the ACC, was also investigated. We found that the expression of LTP and network LTP was significantly impaired in the s845A mice, but not in the s831A mice. By contrast, basal synaptic transmission and NMDA receptor-mediated responses were not affected. Furthermore, to uncover potential information under the current acquired data, a new method for reconstruction and better visualization of the signals was developed to observe the spatial localizations and dynamic temporal changes of fEPSP signals and multiple LTP responses within the ACC circuit. Our results provide strong evidence that PKA phosphorylation of the GluA1 is important for the network LTP expression in the ACC. Previous studies have shown that PKA and PKC phosphorylation of AMPA receptor GluA1 plays critical roles in LTP in the hippocampus, while the roles of GluA1 phosphorylation in the cortex remain unknown. In the present study, by combining a 64-channel multielectrode system and a novel analysis and visualization method, we observed the accurate spatial localization and dynamic temporal changes of network fEPSP signals and LTP responses within the ACC circuit and found that PKA phosphorylation, but not PKC phosphorylation, of the GluA1 is required for LTP in the ACC.

Protein Kinase C Lambda Mediates Acid-Sensing Ion Channel 1a-Dependent Cortical Synaptic Plasticity and Pain Hypersensitivity

“…Brain slice preparation and patch-clamp recordings. Experiments were performed on ACC slices as described previously (Koga et al, 2015;Song et al, 2017). Briefly, after decapitation, the mouse brain was quickly removed and placed in well-oxygenated (95% O 2 /5% CO 2 , v/v) ice-cold aCSF containing the following (in mM): 125 NaCl, 2.5 KCl, 12.5 D-glucose, 1 MgCl 2 , 2 CaCl 2 , 1.25 NaH 2 PO 4 , and 25 NaHCO 3 , pH 7.35-7.45.…”

“…Three coronal brain slices (300 m) were obtained at the level of ACC with a vibratome (Leica Microsystems VT 1000S) and incubated at 31°C in oxygenated aCSF for at least 1 h. Then the brain slice was transferred to a recording chamber placed on the stage of a microscope (Olympus, BX51WI) equipped with an infrared differential interference contrast video monitor. EPSCs were recorded from layer II/III pyramidal neurons with an Axon 200B amplifier (Molecular Devices), and the stimulations were delivered by a bipolar tungsten stimulating electrode placed in layer V/VI of the ACC (Song et al, 2017). The recording pipettes (3-5 M⍀) were filled with a solution containing the following (in mM): 132.5 Cs-gluconate, 17.5 CsCl, 2 MgCl 2 , 0.5 EGTA, 10 HEPES, 4 Mg-ATP, and 5 QX-314 chloride (280 -300 mOsm, pH 7.2 with CsOH).…”

“…The fEPSPs recorded at the remaining microelectrodes were amplified by a 64-channel amplifier, displayed on the monitor screen, and stored on the hard disk of a microcomputer for offline analysis. For LTP induction, after the baseline synaptic responses were stabilized for at least 30 min, a theta burst stimulation (TBS) protocol (5 bursts at 5 Hz, repeated 5 times at 10 s intervals, 4 pulses at 100 Hz for each burst) was delivered with the stimulation intensity eliciting 40%-60% of the maximum response (Li et al, 2010;Song et al, 2017;Ko et al, 2018). For LTD induction, stable baseline responses were recorded for at least 20 min before delivery of the low-frequency stimulation (LFS) protocol (1 Hz, 900 pulses) (Liu and Zhuo, 2014).…”

A unified computational model for cortical post-synaptic plasticity

“…We carried out additional simulations with the obtained models using HFS protocol. The models fitted for data from EC (data sets EC-1 and EC-2, [Ma et al, 2008]), BC [Hardingham et al, 2003], ACC [Song et al, 2017], and LTP-expressing cultured cortical neurons (data set AC-1, [Kotak et al, 2007]) predicted a steady increase in response to HFS, while models fitted for other cortical data predicted a mixture of LTP, LTD, and no change (Fig. 10A).…”

Sex difference in synaptic plasticity in the anterior cingulate cortex of adult mice

“…Before experiments, we treated the surface of the MED64 probe with 0.1% polyethyleneimine (Sigma, St. Louis, MO; P-3143) in 25 mmol/L borate buffer (pH 8.4) overnight at room temperature. Then we used sterile distilled water to flush the probe surface three times to remove harmful substances that affect the activity of brain slices [13,14].…”