Perforated postsynaptic densities: probable intermediates in synapse turnover.

Abstract

The molecular layer of the dentate gyrus of normal rats shows a large incidence ofperforated postsynaptic densities (PSDs). The perforations or discontinuities occur almost exclusively in PSDs located in spines showing a U-or W-shaped junctional profile (complex PSDs). Perforated PSDs account for 16-25% of the total complex PSD profiles in young adult rats and 12-29% of those in aged animals. The frequency of perforations in the inner molecular layer of the dentate gyrus undergoes significant changes during a cycle of nondegenerative synapse turnover induced by ipsilateral ablation ofthe entorhinal cortex. During the first 2 days postlesion nonperforated PSDs (simple PSDs) decrease sharply, whereas perforated PSDs change little. However, at later times (4-10 days) there is a significant increase in the number of perforated PSDs that balances the number of simple PSDs lost. Beyond 10 days postlesion the proportion of both types of PSD is restored slowly to normal-i.e., nonperforated PSDs increase in number and perforated PSDs decrease, returning to the values in unoperated animals by 120 days postlesion. This inverse relationship between small nonperforated PSDs and large perforated PSDs suggests a precursor-product relationship between them. We propose that perforated PSDs are intermediates in an ongoing cycle of synapse turnover that is a part of the normal maintenance and adaptation of the nervous system. Synapse replacement (synapse turnover) appears to be part of the normal program both for the maintenance ofthe peripheral and central nervous systems of adult vertebrates and for their adaptation to changing situations. Experimental evidence for the existence of this process is widespread (reviewed in refs. 1 and 2) but indirect, depending on inferences derived from the observation of characteristic degenerating and regenerating synaptic profiles. In normal animals the proportion of these profiles is generally small and furthermore, synapse turnover may occurwithout display ofsuch structures. Perhaps the greatest difficulty in studying synapse turnover in the adult is to devise a method to trigger it reliably in a statistically meaningful neuronal population. We have found that unilateral lesions of the entorhinal cortex initiate a cycle ofsynapse turnover in areas of the hippocampal formation that do not receive afferent input from the injured cortex (3, 4). The replacement ofsynapses thus induced is similar to the natural turnover process in unoperated animals in that degenerating profiles are never observed and synapse disconnection does not require the loss ofeither axonal or dendritic counterparts. However, an advantage with respect to the natural process is that synapse turnover can be elicited at will in a large synapse population and studies on the intermediate stages are possible. Here, we report the use of this method to study the structural changes that occur in the postsynaptic densities (PSDs) of asymmetric synapses in the hippocampal dentate gyrus during one cycle of synapse turnover.PS...

Repeated confocal imaging of individual dendritic spines in the living hippocampal slice: evidence for changes in length and orientation associated with chemically induced LTP

“…Indeed, the formation of new spines appeared to be extremely rare events over our interval of observation. In addition, in contrast to previous suggestions (Nieto-Sampedro et al, 1982;Carlin and Siekevitz, 1983;Dyson and Jones, 1984;Trommald et al, 1990;Geinisman, 1991), we observed no splitting or bifurcation of preexisting spines with LTI? Nevertheless, our observations do not rule out .…”

Structural role of zinc ions bound to postsynaptic densities

“…These observations strongly suggest that the PSD in the brain is a plastic structure. The plasticity of the PSD structure has been proposed as one of the mechanisms underlying longterm changes in synaptic function (Nieto-Sampedro et al 1982;Lisman and Harris 1993;Edwards 1995). That the structure of the PSD is plastic in vivo is consistent with two recent reports (Lai et al 1999;Sui et al 2000).…”

Interprotein Disulfide Bonds Formed During Isolation Process Tighten the Structure of the Postsynaptic Density

“…Similarly, the contents of ATPase, Nethylmaleimide-sensitive fusion protein, heat shock cognate protein-70, brain-derived neurotrophic factor receptor, and protein kinases in the PSD have been reported to increase following transient cerebral ischemia (Hu et al, 1998). That the PSD in vivo is made with proteins held together by reversible forces is also consistent with the findings that the structure of the PSD in the brain undergoes rapid alterations in response to synaptic activities (e.g., Nieto-Sampedro et al, 1982;Rees et al, 1985;Desmond and Levy, 1986;Geinisman et al, 1991; for reviews, see Lisman and Harris, 1993;Edwards, 1995).…”