doi:10.1016/S0006-8993(02)03188-8
Copyright © 2002 Elsevier Science B.V. All rights reserved.
Research report
Presynaptic group III mGluR modulation of short-term plasticity in the lateral perforant path of the dentate gyrus in vitro
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Anthony M. Rusha, 1, John Kilbridea, 1, Michael J. Rowanb and Roger Anwyl
,
, a
a Department of Physiology, Trinity College, Dublin 2, Ireland
b Experimental Therapeutics, Trinity College, Dublin 2, Ireland
Accepted 3 July 2002.
Available online 23 August 2002.
Author Keywords: Short-term depression; Facilitation; Lateral perforant path; Dentate gyrus; Group III metabotropic glutamate receptor
Neuroscience classification codes: Excitable membranes and synaptic transmission, Presynaptic mechanisms
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Fig. 1. Brief high frequency trains evoke short-term depression of field excitatory postsynaptic potentials (EPSPs). (A) The graph shows the normalised amplitude of the EPSP evoked during trains of 10 stimuli at frequencies of 1, 5, 50, 75 and 100 Hz in the lateral perforant path of the dentate gyrus. Note the initial facilitation during stimulation at 50 and 75 Hz. The traces show EPSPs evoked during 1 and 50 Hz. (B) Shows a curve of the amplitude of the normalised steady-state depressed amplitude of the EPSPs plotted against frequency in the lateral (filled circles) and medial (open circles) perforant paths. The extent of short-term depression evoked by the high frequency trains increases with frequency in both paths, but the extent of the steady-state level of depression is much smaller in the lateral than the medial perforant path at all frequencies. (C) Shows a curve of the amplitude of the EPSP per unit time plotted against frequency for EPSPs in the lateral (filled circles) and medial (open circles) perforant paths.
Fig. 2. Activation of group III mGluR by -AP4 inhibits the field EPSP in a dose-dependent manner in the lateral perforant path of the dentate gyrus. (A) The graph shows the increasing inhibition of the EPSPs by 0.5, 1.0, 5 and 10 μM -AP4 (average of data from nine cells). The traces show examples of EPSPs prior to and following application of 10 μM -AP4. (B) The dose–response curve of the inhibition of the EPSP by -AP4. The curve was fitted with a one-site binding hyperbola, Y=BmaxX/(Kd+X) where Bmax is the maximal binding, and Kd is the concentration of ligand required to reach half-maximal binding. The IC50 for the inhibitory effect of -AP4 was 2.4 μM. Each point plots the mean values for 5–8 values.
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Fig. 3. The mGluR group III agonist -AP4 inhibits short-term depression evoked at 50 Hz, but not 1 Hz in the lateral perforant path of the dentate gyrus. (A) Shows the absolute amplitude of the EPSPs in a train of 10 evoked at 1 Hz in control (open circles), in the presence of 2.4 μM -AP4 (filled circles) and in the presence of 10 μM -AP4 (filled squares). The traces show EPSPs evoked at 1 Hz in control, 2.4 μM -AP4 and 10 μM -AP4. (B) Shows the amplitude of the normalised EPSPs in the train evoked at 1 Hz in control (open circles), in 2.4 μM -AP4 (filled circles) and in 10 μM -AP4 (filled squares). (C) Shows the absolute amplitude of the EPSPs in the train evoked at 50 Hz in control (open circles), in the presence of 2.4 μM -AP4 (filled circles) and in the presence of 10 μM -AP4 (filled triangles). The traces show EPSPs evoked at 50 Hz in control, 2.4 μM -AP4 and 10 μM -AP4. (D) Shows the amplitude of the normalised EPSPs in the train evoked at 50 Hz in control (open circles), in 2.4 μM -AP4 (filled circles) and in 10 μM -AP4 (filled squares).
Fig. 4. The group III mGluR agonist -AP4 reduces the steady-state depressed amplitude of the EPSP at frequencies above 5 Hz in the lateral perforant path. (A) Shows a graph of the inhibition of the steady-state depressed amplitude of the EPSP plotted against frequency in 2.4 μM -AP4 (open circles) and 10 μM -AP4 (filled circles). (B) A curve relating the EPSP per unit time to frequency in control (open circles), 2.4 μM -AP4 (filled circles) and 10 μM -AP4 (squares).
1 These authors contributed equally to the paper.
Corresponding author. Tel.: +353-1-608-1624; fax: +353-1-679-3545; email:ranwyl@mail.tcd.ie