| Abstract No.: | C-B3027 |
| Country: | Canada |
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| Title: | INHIBITORY PLASTICITY IS SUFFICIENT FOR THE EXPRESSION OF PATHWAY-RESTRICTED LTP IN AREA CA1 OF THE RAT HIPPOCAMPUS |
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| Authors/Affiliations: | 1 Jake Ormond*; 1 Melanie Woodin;
1 University of Toronto, ON, Canada
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| Content: | Objectives: Long-term potentiation (LTP) of glutamatergic transmission in the hippocampus is widely accepted as a cellular substrate for learning and memory. Though most often induced experimentally using high frequency presynaptic stimulation, LTP can also be induced in area CA1 of the hippocampus by low-frequency correlated pre- and postsynaptic spiking thought to mimic physiological patterns of activity. Interestingly, correlated activity can also induce a form of inhibitory plasticity in which the equilibrium potential for GABAA-mediated currents (EGABA) is depolarized, effectively weakening inhibition. Because stimulation in area CA3 results in nearly simultaneous activation of glutamatergic and GABAergic synapses onto CA1 neurons, we sought to determine whether the depolarization of EGABA induced by correlated activity could alone produce the increase in amplitude of postsynaptic potentials commonly associated with LTP.
Materials and Methods: 50-70 day-old male Sprague Dawley rats were anaesthetized with a mixture of ketamine and xylazine, and cardiac perfused with ice-cold cutting solution (standard ACSF with sucrose replacing NaCl, calcium concentration halved, magnesium concentration doubled). The hippocampus was dissected out and 400 um slices cut on a vibratome. All recording were made in ACSF at 37C using whole-cell recording techniques. CNQX was applied to the bath to block AMPAR currents, as was APV for NMDAR currents, and gabazine for GABAAR currents. Autocamtide-2 related inhibitory peptide (AIP) was applied intracellularly through the whole-cell pipette to block CaMKII activation. Electrical stimulation was applied using ACSF filled patch electrodes.
Results: We found that blocking CaMKII activation with the inhibitory peptide AIP had no effect on the induction or expression of spike-timing dependent GABAergic plasticity, in contrast to glutamatergic LTP, which was completely blocked. When both glutamatergic and GABAergic transmission were left intact under conditions of CaMKII blockade, correlated activity resulted in a long-lasting increase in the amplitude of the depolarizing phase of the postsynaptic potential. Additionally, we performed 2-pathway experiments to investigate the synapse specificity of changes in EGABA. We found that when plasticity was induced at somatic synapses, plasticity did indeed spread to unstimulated synapases. However, we also observed an increase in inhibitory conductance only at the unstimulated pathway, which appeared to counteract the reduction in inhibitory strength due to the depolarization of EGABA. When 2-pathway experiments were conducted with intact gluatamatergic transmission, no change in EPSP amplitude was observed at the second pathway.
Conclusion: The depolarization of EGABA is sufficient to produce the long-lasting increase in amplitude of the postsynaptic potential induced by spike-timing protocols in area CA1 of the hippocampus. While the change in EGABA does spread to other nearby synapses, an increase in GABAergic conductance at these sites acts to maintain a consistent level of inhibition, thereby confining LTP expression to the stimulated pathway.
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