Prior activation of inositol 1,4,5-trisphosphate receptors suppresses the subsequent induction of long-term potentiation in hippocampal CA1 neurons

Abstract

We investigated the role of inositol 1,4,5-trisphosphate receptors (IP 3 Rs) activated by preconditioning low-frequency afferent stimulation (LFS) in the subsequent induction of long-term potentiation (LTP) in CA1 neurons in hippocampal slices from mature guinea pigs. Induction of LTP in the field excitatory postsynaptic potential or the population spike by the delivery of high-frequency stimulation (HFS, a tetanus of 100 pulses at 100 Hz) to the Schaffer collateral-commissural pathway to CA1 neuron synapses was suppressed when group I metabotropic glutamate receptors (mGluRs) were activated prior to the delivery of HFS. LTP induction was also suppressed when CA1 synapses were preconditioned 60 min before HFS by LFS of 1000 pulses at 1 Hz and this effect was inhibited when the test stimulation delivered at 0.05 Hz was either halted or applied in the presence of an antagonist of N-methyl-D-aspartate receptors, group I mGluRs, or IP 3 Rs during a 20-min period from 20 to 40 min after the end of LFS. Furthermore, blockade of group I mGluRs or IP 3 Rs immediately before the delivery of HFS overcame the effects of the preconditioning LFS on LTP induction. These results suggest that, in CA1 neurons, after a preconditioning LFS, activation of group I mGluRs caused by the test stimulation results in IP 3 Rs activation that leads to a failure of LTP induction.Activity-dependent modification of synaptic efficacy is fundamental to the storage of information in the brain. Long-term potentiation (LTP) in the hippocampus is a long-lasting change in synaptic efficacy and is thought to play an important role in learning and memory (Bliss and Collingridge 1993). The highfrequency stimulation (HFS)-induced LTP at CA1 synapses is generally believed to be triggered by the influx, during HFS, of Ca 2+ into the postsynaptic neuron through channels coupled to N-methyl-D-aspartate glutamate receptors (NMDARs), and this increase in the intracellular Ca 2+ concentration ([Ca 2+ ] i ) activates Ca 2+ /calmodulin-dependent protein kinase II (CaMKII) to phosphorylate the GluA1 subunit of the a-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPAR) in postsynaptic neurons (Alford et al. 1993;Bliss and Collingridge 1993).Activation of metabotropic glutamate receptors (mGluRs) can facilitate the HFS-induced LTP in CA1 neurons (Behnisch and Reymann 1993) and is, therefore, also believed to be a significant functional component of the cellular mechanisms of LTP formation in hippocampal CA1 neurons (Bashir et al. 1993). Stimulation of group I mGluRs on hippocampal neurons activates phospholipase C, which hydrolyses the inositol lipid precursor in the postsynaptic plasma membrane into inositol 1,4,5-trisphosphate (IP 3 ) and diacylglycerol, the former opening IP 3 receptor (IP 3 R) channels and the latter activating protein kinase C (PKC) (Ben-Ari et al. 1992;Nakanishi 1992). IP 3 Rs act as IP 3 -gated Ca 2+

Intracellular Ca2+Release and Synaptic Plasticity: A Tale of Many Stores

“…In addition to regulating LTD, IP 3 Rs have been reported to mediate other related forms of plasticity, including depotentiation and LTP suppression, which is a metaplastic effect where low frequency stimulation, delivered prior to tetanic stimulation, prevents the subsequent induction of LTP (Fujii and others 2000; Fujii and others 2016; Yamazaki and others 2012).…”

Lithium modulates the muscarinic facilitation of synaptic plasticity and theta-gamma coupling in the hippocampal-prefrontal pathway

“…A common mechanism underlying lithium modulation on both low-and high-dose pilocarpine (as in the lithium-pilocarpine model of limbic seizures) may be related to the inositol cascade (Kofman et al, 1993;Morrisett et al, 1987;Sherman et al, 1985Sherman et al, , 1986 and the accumulation of inositol 1,4,5-triphosphate (IP3; Sade et al, 2016;Lee et al, 1992;Sun et al, 1992;Whitworth et al, 1990). In fact, genetic (Fujii et al, 2000(Fujii et al, , 2016Itoh et al, 2001;Nagase et al, 2003) and pharmacological studies (Taufiq et al, 2005) have shown that IP3Rs modulate hippocampal synaptic plasticity similarly to our study: LTP attenuation and LTD facilitation. Further discussion on inositol or phosphoinositol roles in our findings would be rather speculative, since we…”

IP3 receptor mutations and brain diseases in human and rodents

“…Therefore, the dysfunction of a specific isoform of IP 3 R distinctly affects the physiological functions in vivo. For example, defects in the IP 3 R1 function result in cerebellar ataxia (Matsumoto et al 1996) and impaired synaptic plasticity (Inoue et al 1998;Nishiyama et al 2000;Fujii et al 2016). IP 3 R2 is associated with anhidrosis (Klar et al 2014), osteoclast formation (Kuroda et al 2008), and decrease in cardiac function (Drawnel et al 2012;Nakayama et al 2010;Vervloessem et al 2015).…”