The induction of long-term potentiation and depression depends upon associative interactions between synapses that converge on individual dendrites. The distance over which these associative interactions occur is limited. The present study evaluates whether this limitation is regulated by synaptic inhibition. We evaluated the associative interactions between two inputs that terminate on different proximo-distal locations along the dendrites of dentate granule cells in the presence of the raminobutyric acid (GABA) antagonist bicucufline methiodide. Local blockade of GABAergic inhibition enhanced associative interactions between nonoverlapping inputs, compared to within-animal control sites, where inhibitory transmission was intact. The results suggest that synaptic inhibition limits interactions between excitatory synapses by creating current shunts that limit the spread of depolarization within the dendritic tree.Long-term potentiation (LTP) and long-term depression (LTD) are two forms ofactivity-dependent synaptic plasticity characteristic of glutamatergic synapses in many brain areas. These synaptic changes are believed to contribute to information storage in the brain, and their credibility as a mechanism of memory derives in part from their associative nature. LTP requires for its induction both presynaptic activation and postsynaptic depolarization (1). Because postsynaptic membrane potential is controlled largely by synaptic input, LTP represents an interaction between active excitatory terminals converging on a common target neuron. One form of LTD occurs in synapses that are inactive during synaptically driven postsynaptic depolarization (2, 3) and is therefore an interaction between active and inactive excitatory synapses.In at least some cases, these associative interactions are spatially restricted to portions ofthe dendritic arbor on which the interacting synapses converge. This was demonstrated by taking advantage of the laminar arrangement of inputs to the dentate gyrus (DG) of the rat hippocampus (4, 5 METHODS Male Sprague-Dawley rats (250-400 g) were anesthetized with urethane (1.2-1.6 g/kg) and placed in a stereotaxic apparatus. Bipolar stimulating electrodes (twisted wire) were placed in the medial and lateral entorhinal cortices (8.6 mm posterior, 3.1 mm lateral and 8.5 mm posterior, S5.5 mm lateral, respectively, from bregma) to activate inputs to the middle and distal portions, respectively, of the granule cell dendrites (Fig. 1). The wide separation of stimulation sites was intended to activate populations of synapses that were well separated along the dendrite, so as to minimize interaction at the control sites (4, 5).Two recording micropipettes were positioned in the hilus of the ipsilateral DG. The first, containing 0.9o NaCl, was inserted 3.5 mm posterior and 1.5 mm lateral to bregma. Once satisfactory responses from the two stimulating electrodes were obtained from this electrode, the second recording pipette, containing 8 mM bicuculline methiodide in 0.9%o NaCl, was placed :1....
1. We tested the hypothesis that long-term synaptic potentiation (LTP)-associated excitatory postsynaptic potential (EPSP)/spike dissociation in the dentate gyrus (DG) is determined, in part, by changes in the feed-forward inhibition evoked by perforant path (PP) stimulation. The dentate commissural pathway (CP) and the PP activate a common pool of interneurons. Therefore a change in synaptic efficacy in the inhibitory circuit due to activation of one pathway could lead to changes in inhibitory efficacy in the other. The relationship between changes in feed-forward inhibition in the CP and EPSP/spike (E-S) functions in the PP should provide information about the site(s) of synaptic modification. 2. In urethan-anesthetized rats, we measured the inhibition of evoked PP population spikes by the CP at interstimulus intervals of 6 and 12 ms. This measure of commissural inhibition and conventional E-S functions for the PP input to the DG were obtained before and after 1) PP tetany (400 Hz, 8-pulse trains) at low, medium, and high stimulus intensities, and 2) CP tetany (200 Hz, 7-pulse trains). 3. Low-intensity PP conditioning (just above population spike threshold) led to a decrease in CP inhibition and large left shifts of the E-S function. High- and medium-intensity PP conditioning yielded increases in commissural inhibition and smaller leftward E-S shifts. 4. Commissural conditioning led to increases in commissural inhibition and inconsistent changes in the E-S functions.(ABSTRACT TRUNCATED AT 250 WORDS)
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