Long‐term synaptic morphometry changes after induction of long‐term potentiation and long‐term depression in the dentate gyrus of awake rats are not simply mirror phenomena

Abstract

Mechanisms of expression of long-term synaptic plasticity are believed to involve morphological changes of the activated synapses and remodelling of connectivity. Here, we investigated changes in synaptic and neuronal parameters in the dentate gyrus 24 h after induction of long-term potentiation (LTP) and long-term depression (LTD) in awake rats. In dentate granule cells, tetanization of the medial or lateral perforant paths induces LTP in specific synaptic bands along the dendrites in the middle and outer molecular layers, respectively, and tetanization of the lateral path induces robust LTD heterosynaptically in the middle molecular layer. This functional segregation allowed us to assess morphological changes associated with LTP and LTD in each pathway in the same population of neurons. Electron microscopy and unbiased counting methods were used to estimate neuronal density, axospinous, axodendritic and perforated synapse density, multiple synapse bouton density and postsynaptic density (PSD) area. Whereas there was no change in neuronal density, PSD area and multiple synapse boutons 24 h after either LTP or LTD, there was a noninput-specific increase in unperforated axospinous synapses after both LTP and LTD. However, we found that LTP of the medial, but not lateral, perforant path is associated with a specific increase in perforated axospinous synapses in the potentiated area. We also show that heterosynaptic LTD is associated with an input-specific increase in axodendritic synapse density. These results suggest that each perforant pathway may differ with respect to the nature of LTP-induced long-term changes and show that morphologically LTD is not simply the converse of LTP.

N-methyl-d-aspartate receptor independent changes in expression of polysialic acid-neural cell adhesion molecule despite blockade of homosynaptic long-term potentiation and heterosynaptic long-term depression in the awake freely behaving rat dentate gyrus

“…All electrophysiological data were obtained in awake rats and experimental procedures were similar to those previously reported (Mezey et al, 2004). In short, after 3 days of habituation to the recording chamber (30 min each day) during which input/output curves and convergence and summation tests were carried out, a pre-HFS baseline was recorded by stimulating alternately the two pathways at 15 s intervals for 20 min using test intensities (mean 400 mA, 80-120 ms) to evoke MPP and LPP EPSP slopes of approximately half its maximum.…”

“…1) and was blocked by the presence of the NMDA receptor antagonist CPP immediately (magnitude at 30 min 22.64 + 4.06% change; significant difference with LTP groups, F 1,11 ¼ 30.8, P , 0.001) and for 24 h (6.62 + 2.83% change, n ¼ 4). As described in our previous investigations (Doyere et al, 1997;Mezey et al, 2004), potentiation of the LPP (21.73 + 8.30% change at 2 h, n ¼ 5; 39.80 + 8.60% change at 24 h, n ¼ 4; data not shown) resulted immediately in heterosynaptic LTD of the MPP with a magnitude of 220.57 + 3.30% change (n ¼ 9) 30 min post-HFS, which was maintained at 2 h (214.30 + 3.69% change) and at 24 h (210.36 + 1.56% change at 24 h; Fig. 1).…”

“…kg 21 , i.p.) and prepared for chronic recording as described previously (Doyere et al, 1997;Mezey et al, 2004). Briefly, animals were placed on a stereotaxic apparatus and kept at a constant temperature of 378C.…”

The N-methyl-d-aspartate receptor antagonist CPP alters synapse and spine structure and impairs long-term potentiation and long-term depression induced morphological plasticity in dentate gyrus of the awake rat

“…A quantitative 2-dimensional ultrastructural study in vivo looked at morphological correlates of heterosynaptic LTD in dentate gyrus of the awake rat (Mezey et al, 2004) and showed that LTD was not simply the converse of LTP. A non input-specific increase was found in unperforated axospinous synapses 24h after both LTP and LTD while the major effect of LTD alone was an input-specific increase in axodendritic synapse density.…”

Stress suppresses and learning induces plasticity in CA3 of rat hippocampus: A three-dimensional ultrastructural study of thorny excrescences and their postsynaptic densities

“…Changes in synaptic and dendritic structure are believed to underlie synaptic plasticity in the hippocampus (Moser et al, 1994(Moser et al, , 1997Stewart et al, 2000;O'Malley et al, 2000;Nikonenko et al, 2002;Eyre et al, 2003;Muller and Nikonenko, 2003;Harris et al, 2003;Mezey et al, 2004;Popov et al, 2004). In rats stressed for 3-4 weeks, synaptic changes occur in CA3, including alterations in mossy fibre terminals (Magariños et al, 1997), a loss of synapses and a reduction in the surface area of postsynaptic densities (Sousa et al, 2000).…”