| Abstract No.: | A-B1074 |
| Country: | Canada |
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| Title: | INHIBITORY SYNAPTIC PLASTICITY IN THE HIPPOCAMPUS |
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| Authors/Affiliations: | 1 Trevor Balena*; 1 Melanie Woodin;
1 University of Toronto, ON, Canada
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| Content: | Objectives: The influx of calcium ions (Ca2+) into the postsynaptic cell is necessary for synaptic plasticity induction via spike timing-dependent plasticity (STDP). While the nature of the relationship between the postsynaptic current amplitude and the magnitude of the postsynaptic Ca2+ influx has been well characterized at glutamatergic (excitatory) synapses, comparatively little is known about inhibitory synapses at which gamma-aminobutyric acid (GABA) is released. In the present work we characterize the correlation between postsynaptic Ca2+ influx and GABAergic current amplitude during STDP induction, and use pharmacological agents to determine which voltage-gated calcium channels (VDCCs) are responsible for this influx.
Materials & Methods: Dual patch clamp recordings were made from E18 Sprague-Dawley rat hippocampi cultured at low density. Each cell in a pair was stimulated in turn at 0.05 Hz to determine if GABA was being released, and current-voltage (IV) curves were constructed to ascertain the reversal potential of the GABAergic current (EGABA). Synaptic plasticity was induced by injecting current pulses in order to induce the cells to fire in a correlated fashion (5 ms apart) at 5 Hz.
Neurons were loaded with the Ca2+ indicator dye Fluo4-AM through 30 minutes incubation prior to recording. When required, Nickel(II) Chloride (NiCl2; a blocker of T-type VDCCs) was perfused into the bath solution.
Results: Postsynaptic current amplitude at glutamatergic synapses is known to be positively correlated with the magnitude of the postsynaptic Ca2+ influx during STDP induction. In the present work, we found that the opposite is true for GABAergic synapses; weak synapses (defined as those with a postsynaptic current amplitude < 50 pA) resulted in a significantly larger postsynaptic Ca2+ influx than did stronger synapses (those with a postsynaptic current amplitude > 50 pA) during STDP induction. There was also a significant difference in the rise time of the Ca2+ influx (the time taken for the influx to reach its maximum) between weak and strong synapses.
NiCl2 perfusion was found to abolish the larger Ca2+ influx found at weaker GABAergic synapses; in the presence of the drug, the postsynaptic Ca2+ influx during STDP induction was now no different than that seen in the absence of GABA release.
Conclusion: We have demonstrated that the strength of GABAergic synapses is inversely correlated with the magnitude of the postsynaptic Ca2+ influx that occurs during STDP induction. The temporal properties of the Ca2+ rise also depend on the strength of the synapse. These differences are abolished by the T-type Ca2+ channel blocker NiCl2.
T-type Ca2+ channels are activated by membrane hyperpolarization, whereas the majority of VDCC subtypes are activated by membrane depolarization. Thus, it seems that small GABAergic currents hyperpolarize the membrane and open T-type channels. This results in additional Ca2+ influx, which is combined with the influx through depolarization-gated VDCCs that open as the cell fires action potentials. By contrast, large GABAergic currents hyperpolarize the membrane to such an extent that far fewer depolarization-gated VDCCs open, and the total Ca2+ influx is significantly reduced. |
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