Long-term potentiation and long-term depression in hippocampal CA1 neurons of mice lacking the IP(3) type 1 receptor.
ABSTRACT To investigate the role in synaptic plasticity of Ca(2+) released from intracellular Ca(2+) stores, mice lacking the inositol 1,4,5-trisphosphate type 1 receptor were developed and the physiological properties, long-term potentiation, and long-term depression of their hippocampal CA1 neurons were examined. There were no significant differences in basic synaptic functions, such as membrane properties and the input/output relationship, between homozygote mutant and wild-type mice. Enhanced paired-pulse facilitation at interpulse intervals of less than 60 ms and enhanced post-tetanic potentiation were observed in the mutant mice, suggesting that the presynaptic mechanism was altered by the absence of the inositol 1,4,5-trisphosphate type 1 receptor. Long-term potentiation in the field-excitatory postsynaptic potentials induced by tetanus (100 Hz, 1 s) and the excitatory postsynaptic currents induced by paired stimulation in hippocampal CA1 pyramidal neurons under whole-cell clamp conditions were significantly greater in mutant mice than in wild-type mice. Homosynaptic long-term depression of CA1 synaptic responses induced by low-frequency stimulation (1 Hz, 500 pulses) was not significantly different, but heterosynaptic depression of the non-associated pathway induced by tetanus was blocked in the mutant mice. Both long-term potentiation and long-term depression in mutant mice were completely dependent on N-methyl-D-aspartate receptor activity. To rule out the possibility of an effect compensating for the lack of the inositol 1,4,5-trisphosphate type 1 receptor occurring during development, an anti-inositol 1,4,5-trisphosphate type 1 receptor monoclonal antibody that blocks receptor function was diffused into the wild-type cell through a patch pipette, and the effect of acute block of inositol 1,4,5-trisphosphate type 1 receptor on long-term potentiation was examined. Significant enhancement of long-term potentiation was observed compared with after control immunoglobulin G injection, suggesting that developmental redundancy was not responsible for the increase in long-term potentiation amplitude observed in the mutant mouse. The properties of channels that could be involved in long-term potentiation induction were examined using whole-cell recording. N-methyl-D-aspartate currents were significantly larger in mutant mice than in wild-type mice only between holding potentials of -60 and -80 mV. We conclude that inositol 1,4,5-trisphosphate type 1 receptor activity is not essential for the induction of synaptic plasticity in hippocampal CA1 neurons, but appears to negatively regulate long-term potentiation induction by mild modulation of channel activities.
- SourceAvailable from: Andrea C Paula-Lima[Show abstract] [Hide abstract]
ABSTRACT: Significance: Memory is an essential human cognitive function. Consequently, to unravel the cellular and molecular mechanisms responsible for the synaptic plasticity events underlying memory formation, storage and loss represents a major challenge of present day neuroscience. Recent advances: This review article describes first the wide-ranging functions played by intracellular Ca<sup>2+</sup> signals in the activity-dependent synaptic plasticity processes underlying hippocampal spatial memory, to focus next on how the endoplasmic reticulum Ca<sup>2+</sup> release channels, the ryanodine receptors and the inositol 1,4,5-trisphosphate receptors, contribute to these processes. We present a detailed examination of recent evidence supporting the key role played by Ca<sup>2+</sup> release channels in synaptic plasticity, including structural plasticity, and the formation/consolidation of spatial memory in the hippocampus. Critical issues: Changes in cellular oxidative state affect particularly the function of Ca<sup>2+</sup> release channels and alter hippocampal synaptic plasticity and the associated memory processes. Emphasis is placed in this review on how defective Ca<sup>2+</sup> release, presumably due to increased levels of reactive oxygen species, may cause the hippocampal functional defects associated to aging and Alzheimer's disease. Future directions: Additional studies should examine the precise molecular mechanisms whereby Ca<sup>2+</sup> release channels contribute to hippocampal synaptic plasticity and spatial memory formation/consolidation. Future studies should test if redox-modified Ca2+ release channels contribute to generate the intracellular Ca<sup>2+</sup> signals required for sustained synaptic plasticity and hippocampal spatial memory, and whether loss of redox balance and oxidative stress, by altering Ca<sup>2+</sup> release channel function presumably contribute to the abnormal memory processes that occur during aging and Alzheimer's disease.Antioxidants & Redox Signaling 01/2014; · 8.20 Impact Factor
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