NMDA receptor and its dependent synaptic plasticity
NMDA receptors are known to contribute to synaptic LTP (Bliss &
Collingridge, 1993). In the ACC, there are two key forms of LTP: pre-LTP
and post-LTP. For post-LTP, NMDA receptors, including GluN1 and GluN2
(GluN2A-D) isoforms, have been reported to contribute to the induction
of LTP (Bliss et al. , 2016; Li et al. , 2019). LTP
induction protocols such as theta burst stimulation (TBS), pairing
training and spike-EPSPs can induce NMDA receptor-dependent LTP. The
expression of NMDA receptor-dependent LTP requires postsynaptic
modification or insertion of GluA1-containing AMPA receptors.
AC1-dependent, protein kinase A (PKA) phosphorylation of AMPA receptors
GluA1 contributes to LTP (Liauw et al. , 2005; Yamanaka et
al. , 2017; Miao et al. , 2019). A recent study using selective
knock-in mice demonstrates that phosphorylation of AMPA receptor GluA1
plays an important role in synaptic potentiation. However, the same LTP
did not require CaMKII/PKC phosphorylation site serine 831 (Ser831).
These results demonstrate that ACC LTP employs a different mechanism
than hippocampal LTP (Song et al. , 2017).
In addition to post-LTP, an NMDA receptor-independent form of LTP can
also be readily induced in the ACC by paired-pulse low-frequency
stimulation. This form of LTP is resistant to NMDA receptor blockade and
was inhibited in mice lacking the KA receptor GluK1 subunit (Kogaet al. , 2015). Pharmacological experiments using a potent
GluK1-selective KA receptor antagonist, UBP310, further confirmed that
this form of LTP is KA receptor-dependent. Both genetic and
pharmacological evidence consistently indicates that this form of LTP is
pre-LTP. Pre-LTP in the ACC is sensitive to a
hyperpolarization-activated cyclic nucleotide-gated channel inhibitor,
ZD7288 (Koga et al. , 2015). In addition, p42/p44
mitogen-activated protein kinase inhibitors PD98059 and U0126 suppressed
the induction of pre-LTP and did not affect the maintenance of pre-LTP.
The activation of presynaptic extracellular signal-regulated kinase was
required for the induction of pre-LTP (Yamanaka et al. , 2016).