Synaptic Plasticity in Hippocampal CA1 Neurons of Mice Lacking Type 1 Inositol-1,4,5-Trisphosphate Receptors

Abstract

In hippocampal CA1 neurons of wild-type mice, delivery of a standard tetanus (100 pulses at 100 Hz) or a train of low-frequency stimuli (LFS; 1000 pulses at 1 Hz) to a naive input pathway induces, respectively, long-term potentiation (LTP) or long-term depression (LTD) of responses, and delivery of LFS 60 min after tetanus results in reversal of LTP (depotentiation, DP), while LFS applied 60 min before tetanus suppresses LTP induction (LTP suppression). To evaluate the role of the type 1 inositol-1,4,5-trisphosphate receptor (IP3R1) in hippocampal synaptic plasticity, we studied LTP, LTD, DP, and LTP suppression of the field excitatory postsynaptic potentials (EPSPs) in the CA1 neurons of mice lacking the IP3R1. No differences were seen between mutant and wild-type mice in terms of the mean magnitude of the LTP or LTD induced by a standard tetanus or LFS. However, the mean magnitude of the LTP induced by a short tetanus (10 pulses at 100 Hz) was significantly greater in mutant mice than in wild-type mice. In addition, DP or LTP suppression was attenuated in the mutant mice, the mean magnitude of the responses after delivery of LFS or tetanus being significantly greater than in wild-type mice. These results suggest that, in hippocampal CA1 neurons, the IP3R1 is involved in LTP, DP, and LTP suppression but is not essential for LTD. The facilitation of LTP induction and attenuation of DP and LTP suppression seen in mice lacking the IP3R1 indicates that this receptor plays an important role in blocking synaptic potentiation in hippocampal CA1 neurons.

Hippocampal Long-Term Potentiation Is Supported by Presynaptic and Postsynaptic Tyrosine Receptor Kinase B-Mediated Phospholipase Cγ Signaling

“…The fact that in the hippocampus BDNF/TrkB-mediated CA3-CA1 synaptic plasticity seems to be completely accomplished by the PLC␥ pathway is reminiscent of observations at the neuromuscular junction, where NT3-mediated synaptic potentiation is solely dependent on TrkC activated PLC␥ and IP 3 production (Yang et al, 2001). Not in line to these and our data are observations in which IP 3 R type I KO mice show a deficient longterm depression in the cerebellum (Inoue et al, 1998) and normal LTP in the hippocampus (Fujii et al, 2000). This difference could be because of the different stimulus protocol (a weak tetanus was used), the targeting of only IP 3 R type I, and the use of rather young mice before weaning.…”

Enhanced Ryanodine Receptor Recruitment Contributes to Ca2+Disruptions in Young, Adult, and Aged Alzheimer's Disease Mice

“…The functional roles of neuronal Ca 2ϩ stores are becoming increasingly recognized and include modulation of membrane excitability (Davies et al, 1996;Stutzmann et al, 2003), synaptic activity and plasticity (Fujii et al, 2000;Nakamura et al, 2000), and gene transcription (Mellstrom and Naranjo, 2001). However, to gain a better understanding of intracellular Ca 2ϩ signaling disruptions in neuropathology, we attempted to parse the IP 3 R and RyR components to identify interactions between these channels, as well as compartmentalize specific functions ascribed to each.…”

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

“…Our previous studies on hippocampal CA1 neurons in IP 3 R1-lacking mice demonstrated that the induction of LTP by a short tetanus of 10 pulses at 100 Hz or by a standard tetanus of 100 pulses at 100 Hz is facilitated in these mice (Fujii et al 2000b;Nagase et al 2003). Hippocampal CA1 neurons contain high levels of the type 3 RyR (RyR 3 ), but little type 1 or type 2 RyR (Furuichi et al 1994).…”

“…Hulme et al (2012) showed that delivery of two trains of priming HFS (10, 20, 50, or 100 Hz, 10-min interval) to CA1 synaptic inputs reduces the level of LTP induced by a subsequent two trains of HFS (100 Hz, 1-sec trains with a 30-sec interval) and that this effect is attenuated when the HFS are delivered in the presence of an IP 3 R inhibitor. In addition, we ourselves demonstrated that the suppression of LTP induction by a preconditioning LFS (1000 pulses at 1 Hz) given 60 min before an HFS of 100 pulses at 100 Hz is attenuated in hippocampal CA1 neurons in IP 3 R1-deficient mice (Fujii et al 2000b). Recently, we showed that coactivation of NMDARs and IP 3 Rs during a preconditioning LFS results in an increase in the postsynaptic [Ca 2+ ] i in hippocampal CA1 neurons and in the dephosphorylation of synaptic proteins, leading to suppression of subsequent LTP induction (Yamazaki et al 2015).…”

“…Activation of IP 3 Rs during, or after, HFS is involved in the mechanism of LTP induction in hippocampal CA1 neurons (Yoshioka et al 2010). We previously demonstrated that LTP induction in hippocampal CA1 neurons is facilitated in IP 3 R1-lacking mice (Matsumoto et al, 1996) when CA1 synaptic inputs are stimulated by a brief tetanus of 10 pulses at 100 Hz (Fujii et al 2000b) or when CA1 synapses are activated by a standard tetanus of 100 pulses at 100 Hz (Nagase et al 2003). In addition, bath application of 2-aminoethoxydiphenyl borate (2-APB), an antagonist for both IP 3 Rs and store-operated calcium (SOC) channels (Maruyama et al 1997;Iwasaki et al 2001;Bootman et al 2002;Peppiatt et al 2003), or of a-methyl-4-carboxyphenylglycine (MCPG), a wide-spectrum mGluR antagonist (Pin and Duvoisin 1995), during brief HFS (10 or 15 pulses at 100 Hz) significantly increases the magnitude of the LTP in hippocampal CA1 neurons (Taufiq et al 2005).…”