Synaptic degeneration and remodelling after fast kindling of the olfactory bulb

Kindling of the olfactory bulb using a novel fast protocol (within 24 h) was studied in rats. In target brain regions, the effects of kindling were measured on the concentration of glial fibrillary acidic protein (GFAP) by dot-blot and on the concentrations of neural cell adhesion molecule (NCAM) and the 25 kDa synaptosomal associated protein of the D3 immunoprecipitate (D3(SNAP-25)) by crossed immunoelectrophoresis. Bilateral increases in the levels of GFAP, indicating activation of astrocytes, were detected in primary olfactory cortical projection areas, including the piriform cortex, and also in the basolateral amygdala and dentate gyrus, suggesting that these regions may be functionally altered during the kindling process. In the piriform cortex and dentate gyrus increased NCAM/D3(SNAP-25) ratios found ipsilaterally at seven days after kindling probably reflect an elevated rate of synaptic remodelling. At this time, however, an overall pattern of ipsilateral decreases in the synaptic marker proteins NCAM and D3(SNAP-25) indicated that this remodelling occurred on a background of synaptic degeneration. These results confirm previous studies showing that kindling is associated with synaptic remodelling and neuronal degeneration in the hippocampal formation and extends the area of plasticity to include the piriform cortex which is believed to be central to the kindling process.     

Melatonin is Involved in Regulation of the Expression of Neural Cell Adhesion Molecules in the Rat Brain

Cell adhesion molecules play a diverse role in neural development, signal transduction, structural linkage to extracellular and intracellular proteins, synaptic stabilization, neurogenesis, and learning. Neural cell adhesion molecules (NCAM) are members of the immunoglobulin superfamily and are involved in synaptic rearrangements in the mature brain. There are three major NCAM isoforms: NCAM 180, NCAM 140, and NCAM 120. Several studies reported that NCAM play a central role in memory formation. We investigated the effects of melatonin on the expression of NCAM in the hippocampus, cortex, and cerebellum of rats. The levels of NCAM isoforms were determined by Western blotting. After administration of melatonin for 7 days, the expression of NCAM 180 increased both in the hippocampus and in the cortex, as compared with the control. In contrast, in rats exposed to constant illumination for 7 days (a procedure that inhibits endogenous production of melatonin), levels of NCAM 180 dropped in the hippocampus and became undetectable in the cortex and cerebellum. Levels of NCAM 140 in the hippocampus of light-exposed rats also decreased. There was no change in the expression of NCAM 120 in any brain region. This is the first report indicating that melatonin exerts a modulatory effect on the expression of NCAM in brain areas related to realization of cognitive functions. Melatonin may be involved in structural remodeling of synaptic connections during memory and learning processes.     

PSA-NCAM: Synaptic functions mediated by its interactions with proteoglycans and glutamate receptors

Dynamic regulation of glycosylation of the neural cell adhesion molecule (NCAM) by an unusual large negatively charged polysialic acid (PSA) is the major prerequisite for correct formation of brain circuitries during development and for normal synaptic plasticity, learning and memory in the adult. Traditionally, PSA is viewed as a de-adhesive highly hydrated molecule, which interferes with cell adhesion and promotes cellular/synaptic dynamics by steric hindrance. Analysis of synaptic functions of PSA-NCAM highlighted additional features of this molecule. First, PSA promotes interaction of NCAM with heparan sulfate proteoglycans and thus stimulates synaptogenesis. Second, PSA-NCAM modulates glutamate receptors: it restrains activity of extrasynaptic GluN2B-containing NMDA receptors and facilitates activity of a subset of AMPA receptors. Perturbation in polysialylation and/or NCAM expression in mouse models recapitulates many symptoms of human brain disorders such as schizophrenia, depression, anxiety and Alzheimer's disease.     

Distinctive PSA-NCAM and NCAM Hallmarks in Glutamate-Induced Dendritic Atrophy and Synaptic Disassembly

Dendritic and synapse remodeling are forms of structural plasticity that play a critical role in normal hippocampal function. Neural cell adhesion molecule (NCAM) and its polysialylated form (PSA-NCAM) participate in neurite outgrowth and synapse formation and plasticity. However, it remains unclear whether they contribute to dendritic retraction and synaptic disassembly. Cultured hippocampal neurons exposed to glutamate (5 µM) showed a reduced MAP-2 (+) area in the absence of neuronal death 24 h after the insult. Concomitantly, synapse loss, revealed by decreased synaptophysin and post-synaptic density-95 cluster number and area, together with changes in NCAM and PSA-NCAM levels were found. Dendritic atrophy and PSA-NCAM reduction proved NMDA-receptor dependent. Live-imaging experiments evidenced dendritic atrophy 4 h after the insult; this effect was preceded by smaller NCAM clusters (1 h) and decreased surface and total PSA-NCAM levels (3 h). Simultaneously, total NCAM cluster number and area remained unchanged. The subsequent synapse disassembly (6 h) was accompanied by reductions in total NCAM cluster number and area. A PSA mimetic peptide prevented both the dendritic atrophy and the subsequent synaptic changes (6 h) but had no effect on the earliest synaptic remodeling (3 h). Thus, NCAM-synaptic reorganization and PSA-NCAM level decrease precede glutamate-induced dendritic atrophy, whereas the NCAM level reduction is a delayed event related to synapse loss. Consequently, distinctive stages in PSA-NCAM/NCAM balance seem to accompany glutamate-induced dendritic atrophy and synapse loss.     

Stress downregulates hippocampal expression of the adhesion molecules NCAM and CHL1 in mice by mechanisms independent of DNA methylation of their promoters

Stress is an important physiological regulator of brain function in young and adult mammals. The mechanisms underlying regulation of the consequences of stress, and in particular severe chronic stress, are thus important to investigate. These consequences most likely involve changes in synaptic function of brain areas being part of neural networks that regulate responses to stress. Cell adhesion molecules have been shown to regulate synaptic function in the adult and we were thus interested to investigate a regulatory mechanism that could influence expression of three adhesion molecules of the immunoglobulin superfamily (NCAM, L1 and CHL1) after exposure of early postnatal and adult mice to repeated stress. We hypothesized that reduction of adhesion molecule expression after chronic stress, as observed previously in vivo, could be due to gene silencing of the three molecules by DNA methylation. Although adhesion molecule expression was reduced after exposure of C57BL/6 mice to stress, thus validating our stress paradigm as imposing changes in adhesion molecule expression, we did not observe differences in methylation of CpG islands in the promoter regions of NCAM, L1 and CHL1, nor in the promoter region of the glucocorticoid receptor in the hippocampus, the expression of which at the protein level was also reduced after stress. We must therefore infer that severe stress in mice of the C57BL/6 strain downregulates adhesion molecule levels by mechanisms that do not relate to DNA methylation.     

Stress downregulates hippocampal expression of the adhesion molecules NCAM and CHL1 in mice by mechanisms independent of DNA methylation of their promoters

Stress is an important physiological regulator of brain function in young and adult mammals. The mechanisms underlying regulation of the consequences of stress, and in particular severe chronic stress, are thus important to investigate. These consequences most likely involve changes in synaptic function of brain areas being part of neural networks that regulate responses to stress. Cell adhesion molecules have been shown to regulate synaptic function in the adult and we were thus interested to investigate a regulatory mechanism that could influence expression of three adhesion molecules of the immunoglobulin superfamily (NCAM, L1 and CHL1) after exposure of early postnatal and adult mice to repeated stress. We hypothesized that reduction of adhesion molecule expression after chronic stress, as observed previously in vivo, could be due to gene silencing of the three molecules by DNA methylation. Although adhesion molecule expression was reduced after exposure of C57BL/6 mice to stress, thus validating our stress paradigm as imposing changes in adhesion molecule expression, we did not observe differences in methylation of CpG islands in the promoter regions of NCAM, L1 and CHL1, nor in the promoter region of the glucocorticoid receptor in the hippocampus, the expression of which at the protein level was also reduced after stress. We must therefore infer that severe stress in mice of the C57BL/6 strain downregulates adhesion molecule levels by mechanisms that do not relate to DNA methylation.Key words: stress, immunoglobulin superfamily, adhesion molecules, promoter, DNA methylation, hippocampus, glucocorticoid receptor     

The neural cell adhesion molecule and synaptic plasticity

Highly stereotyped patterns of neuronal connections are laid down during the development of the nervous system via a range of activity independent and activity dependent mechanisms. Whereas the coarse hard-wiring of the nervous system appears to rely on molecular recognition events between the neuron, its pathway, and its target, the establishment of precisely patterned functional circuits is thought to be driven by neuronal activity. In this review we discuss the role that the neuronal cell adhesion molecule (NCAM) plays in morphological plasticity. Recent studies on NCAM and its probable species homologue in Aplysia (apCAM) suggests that an individual CAM can function to both promote synaptic plasticity and maintain the structure of the synapse. In the adult brain, changes between stability and plasticity are likely to underlie dynamic morphological changes in synaptic structures associated with learning and memory. In this review we use NCAM as an example to illustrate mechanisms that can change the function of an individual CAM from a molecule that promotes plasticity to one that does not. We also discuss evidence that NCAM promotes plasticity by activating a conventional signal transduction cascade, rather than by modulating adhesion perse. Finally, we consider the evidence that supports a role for NCAM in learning and memory. © 1995 John Wiley & Sons, Inc.     

神经细胞粘连分子和多聚唾液酸在神经发育和再生中的作用

神经系统的形成依赖于细胞间的互相粘连。本文综述了神经细胞粘连分子（ＮＣＡＭ）及其多聚唾液酸（ＰＳＡ）组份对神经发育和再生的作用。ＮＣＡＭ的基本功能是介导细胞粘连,ＰＳＡ则由于其特殊的分子结构而降低细胞间的粘连。研究表明,鸡胚的发育过程中,ＰＳＡ含量在三个关键时期表达的高低决定了运动神经元能否准确地识别和支配肌肉。成年大鼠周围神经损伤后,肌肉内ＮＣＡＭ含量的高低决定于该肌肉的神经支配状况。成年大鼠脑内,切断内嗅皮层与海马的神经联系,发现齿回外分子层ＰＳＡ含量显著增加,并至少可持续６０天。已有的研究资料提示在去神经靶区域ＰＳＡ的重新表达可能有利于移植神经元轴突的生长并与宿主重建突触联系。     

Cytoplasmic domain of NCAM140 interacts with ubiquitin-fold modifier-conjugating enzyme-1 (Ufc1)

The neural cell adhesion molecule NCAM is implicated in different neurodevelopmental processes and in synaptic plasticity in adult brain. The cytoplasmic domain of NCAM interacts with several cytoskeletal proteins and signaling molecules. To identify novel interaction partners of the cytosolic domain of NCAM a protein macroarray has been performed. We identified the ubiquitin-fold modifier-conjugating enzyme-1 (Ufc1) as an interaction partner of NCAM140. Ufc1 is one of the enzymes involved in modification of proteins with the ubiquitin-like molecule ubiquitin-fold modifier-1 (Ufm1). We also observed a partial co-localization of NCAM140 with Ufc1 and Ufm1 and increased endocytosis of NCAM140 in the presence of Ufm1 suggesting a possible ufmylation of NCAM140 and a potential novel function of Ufm1 for cell surface proteins.     

NCAM Function in the Adult Brain: Lessons from Mimetic Peptides and Therapeutic Potential

Neural cell adhesion molecules (NCAMs) are complexes of transmembranal proteins critical for cell–cell interactions. Initially recognized as key players in the orchestration of developmental processes involving cell migration, cell survival, axon guidance, and synaptic targeting, they have been shown to retain these functions in the mature adult brain, in relation to plastic processes and cognitive abilities. NCAMs are able to interact among themselves (homophilic binding) as well as with other molecules (heterophilic binding). Furthermore, they are the sole molecule of the central nervous system undergoing polysialylation. Most interestingly polysialylated and non-polysialylated NCAMs display opposite properties. The precise contributions each of these characteristics brings in the regulations of synaptic and cellular plasticity in relation to cognitive processes in the adult brain are not yet fully understood. With the aim of deciphering the specific involvement of each interaction, recent developments led to the generation of NCAM mimetic peptides that recapitulate identified binding properties of NCAM. The present review focuses on the information such advances have provided in the understanding of NCAM contribution to cognitive function.     

Sequences at the interface of the fifth immunoglobulin domain and first fibronectin type III repeat of the neural cell adhesion molecule are critical for its polysialylation

Polysialic acid is an anti-adhesive glycan that modifies a select group of mammalian proteins. The primary substrate of the polysialyltransferases (polySTs) is the neural cell adhesion molecule (NCAM). Polysialic acid negatively regulates cell adhesion, is required for proper brain development, and is expressed in specific areas of the adult brain where it promotes on-going cell migration and synaptic plasticity. The first fibronectin type III repeat (FN1) of NCAM is required for polysialylation of the N-glycans on the adjacent immunoglobulin-like domain (Ig5), and acidic residues on the surface of FN1 play a role in polyST recognition. Recent work demonstrated that the FN1 domain from the unpolysialylated olfactory cell adhesion molecule (OCAM) was able to partially replace NCAM FN1 (Foley, D. A., Swartzentruber, K. G., Thompson, M. G., Mendiratta, S. S., and Colley, K. J. (2010) J. Biol. Chem. 285, 35056-35067). Here we demonstrate that individually replacing three identical regions shared by NCAM and OCAM FN1, (500)PSSP(503) (PSSP), (526)GGVPI(530) (GGVPI), and (580)NGKG(583) (NGKG), dramatically reduces NCAM polysialylation. In addition, we show that the polyST, ST8SiaIV/PST, specifically binds NCAM and that this binding requires the FN1 domain. Replacing the FN1 PSSP sequences and the acidic patch residues decreases NCAM-polyST binding, whereas replacing the GGVPI and NGKG sequences has no effect. The location of GGVPI and NGKG in loops that flank the Ig5-FN1 linker and the proximity of PSSP to this linker suggest that GGVPI and NGKG sequences may be critical for stabilizing the Ig5-FN1 linker, whereas PSSP may play a dual role maintaining the Ig5-FN1 interface and a polyST recognition site.     

Proteolytic modification of neural cell adhesion molecule (NCAM) by the intracellular proteinase calpain

The neural cell adhesion molecule, NCAM, is concentrated in synaptic regions and thus may contribute to the formation and maintenance of connections between brain cells. We present evidence that the cytoplasmic domain of NCAM can be experimentally modified by the intracellular calcium-dependent proteinase, calpain. This degradation could provide a mechanism for rapidly uncoupling and reorganizing synaptic contacts.     

Neural cell adhesion molecule (NCAM-/-) null mice show impaired sensitization of the startle response

The neural cell adhesion molecule (NCAM) plays important roles in development of the nervous system and in synaptic plasticity and memory formation in the adult. The present study sought to further investigate the role of NCAM in learning by testing habituation and footshock sensitization learning of the startle response (SR) in NCAM null mutant (NCAM-/-) and wildtype littermate (NCAM+/+) mice. Whereas habituation is a form of non-associative learning, footshock sensitization is induced by rapid contextual fear conditioning. Habituation was tested by repetitive presentation of acoustic and tactile startle stimuli. Although NCAM-/- mice showed differences in sensitivity in both stimulus modalities, habituation learning was intact in NCAM-/- mice, suggesting that NCAM does not play a role in the mechanisms underlying synaptic plasticity in the startle pathway. Footshock sensitization was elicited by presentation of electric footshocks between two series of acoustic stimuli. In contrast to habituation, footshock sensitization learning was attenuated in NCAM-/- mice: the acoustic SR increase after the footshocks was lower in the mutant than in wildtype mice, indicating that NCAM plays an important role in the relevant brain areas, such as amygdala and/or the hippocampus.     

Expression of neuronal plasticity markers in hypoglycemia induced brain injury

The expression of neuroplasticity markers was analyzed in four brain regions, namely cerebral hemispheres (CH), cerebellum (CB), brain stem (BS) and diencephalon (DC) from insulin-induced hypoglycemic young adult rats. Significant decrease in neural cell adhesion molecule (NCAM) isoforms and growth-associated protein-43 (GAP-43) was observed following hypoglycemic injury from majority of brain regions studied. The glial fibrillary acidic protein (GFAP) level increased significantly in cerebral hemispheres and diencephalon regions, whereas, synaptophysin level increased in cerebellum, brain stem and diencephalon regions. The selective downregulation of the neuronal plasticity marker proteins (GAP-43 and NCAM), and enhanced expression of GFAP and synaptophysin suggests that in acute hypoglycemia, mechanisms other than energy failure may also contribute to neuronal cell damage in the brain.     

NCAM Mimetic Peptides: Potential Therapeutic Target for Neurological Disorders

The neural cell adhesion molecule (NCAM) plays a pivotal role in the development and maintenance of the nervous system via homophilic (NCAM–NCAM) and heterophilic (NCAM-other molecules) interactions. Many synthetic peptides have been engineered to mimic these interactions and induce NCAM-downstream signaling pathways. Such NCAM mimetics have displayed neuritogenic and neuroprotective properties, as well as synaptic modulation in vitro and in vivo. Furthermore, they have been used successfully in preclinical studies to treat neurological disorders including stroke, traumatic brain injury and Alzheimer’s disease. This review focuses on recent progress in the development of NCAM mimetic peptides, in particular, on establishing C3, plannexin, and FGL as therapeutic candidates for neurological disorders.     

Increase in proportion of hippocampal spine synapses expressing neural cell adhesion molecule NCAM180 following long-term potentiation

Neural recognition molecules such as the neural cell adhesion molecule (NCAM) have been implicated in synaptic plasticity, including long-term potentiation (LTP), sensitization, and learning and memory. The major isoform of NCAM carrying the longest cytoplasmic domain of all NCAM isoforms (NCAM180) is predominantly localized in postsynaptic membranes and postsynaptic densities of hippocampal neurons, with only a proportion of synapses carrying detectable levels of NCAM180. To investigate whether this differential expression of NCAM180 may correlate with distinct states of synaptic activity, LTP was induced by high-frequency stimulation of the perforant path and the percentage of NCAM180 immunopositive spine synapses determined in the outer third of the dentate molecular layer of the dentate gyrus by immunoelectron microscopy. Twenty-four hours following induction of LTP by high-frequency stimulation, the percentage of spine synapses expressing NCAM180 increases from 37% (passive control) to 70%. This increase was inhibited by the noncompetitive N-methyl-D -aspartate receptor antagonist MK801. Following repeated LTP induction at 10 consecutive days with one tetanization each day, 60% of all spine synapses were NCAM180 immunoreactive. Compared to passive control animals, the percentage of NCAM180 expressing synapses in low-frequency stimulated animals decreased from 37% to 28%. Spine synapses in the inner part of the dentate molecular layer not contacted by the afferents of the perforant path did not change the percentage of NCAM180-expressing synapses. The results obtained by the postembedding immunogold staining technique confirmed the difference in NCAM180 expression of spine synapses between passive control and potentiated animals. These observations suggest a role for NCAM180 in synaptic remodeling accompanying LTP. © 1998 John Wiley & Sons, Inc. J Neurobiol 37: 359–372, 1998     

A synthetic peptide ligand of neural cell adhesion molecule (NCAM), C3d,promotes neuritogenesis and synaptogenesis and modulates presynaptic function in primary cultures of rat hippocampal neurons

The neural cell adhesion molecule (NCAM) plays a key role in morphogenesis of the nervous system and in remodeling of neuronal connections accompanying regenerative and cognitive processes. Recently, a new synthetic ligand of NCAM, the C3-peptide, which binds to the NCAM IgI module, has been identified by means of combinatorial chemistry (R?nn, L. C. B, Olsen, M., Ostergaard, S., Kiselyov, V., Berezin, V., Mortensen, M. T., Lerche, M. H., Jensen, P. H., Soroka, V., Saffell, J. L., Doherty, P., Poulsen, F. M., Bock, E., Holm, A., and Saffells, J. L. (1999) Nat. Biotechnol. 17, 1000-1005). In vitro, the dendrimeric form of C3, termed C3d, disrupts NCAM-mediated cell adhesion, induces neurite outgrowth, and triggers intracellular signaling cascades similar to those activated by homophilic NCAM binding. The peptide may therefore be expected to regulate regeneration and synaptic plasticity. Here we demonstrate that in primary cultures of hippocampal neurons: 1) C3d induces a sustained neuritogenic response, the neuritogenic activity of the compound being dependent on the dose, starting time, and duration of peptide application; 2) the peptide triggers the neuritogenic response by forming an adhesive substratum necessary for NCAM-mediated neurite formation and elongation; 3) C3d promotes synapse formation; and 4) C3d modulates the presynaptic function, causing a transient increase of the function at low (2 and 5 microm) doses and a reduction when applied at a higher concentration (10 microm). The effect of the peptide is dependent on the activation of the fibroblast growth factor receptor. We suggest that C3d may constitute a useful lead for the development of compounds for treatment of various neurodegenerative disorders.     

Immunoelectron microscopic localization of the neural recognition molecules L1, NCAM, and its isoform NCAM180, the NCAM-associated polysialic acid, beta1 integrin and the extracellular matrix molecule tenascin-R in synapses of the adult rat hippocampus

We have investigated the possibility that morphologically different excitatory glutamatergic synapses of the "trisynaptic circuit" in the adult rodent hippocampus, which display different types of long-term potentiation (LTP), may express the immunoglobulin superfamily recognition molecules L1 and NCAM, the extracellular matrix molecule tenascin-R, and the extracellular matrix receptor constituent beta1 integrin in a differential manner. The neural cell adhesion molecules L1, NCAM (all three major isoforms), NCAM180 (the largest major isoform with the longest cytoplasmic domain), beta1 integrin, polysialic acid (PSA) associated with NCAM, and tenascin-R were localized by pre-embedding immunostaining procedures in the CA3/CA4 region (mossy fiber synapses) and in the dentate gyrus (spine synapses) of the adult rat hippocampus. Synaptic membranes of mossy fiber synapses where LTP is expressed presynaptically did not show detectable levels of immunoreactivity for any of the molecules/epitopes studied. L1, NCAM, and PSA, but not NCAM180 or beta1 integrin, were detectable on axonal membranes of fasciculating mossy fibers. In contrast to mossy fiber synapses, spine synapses in the outer third of the molecular layer of the dentate gyrus, which display postsynaptic expression mechanisms of LTP, were both immunopositive and immunonegative for NCAM, NCAM180, beta1 integrin, and PSA. Those spine synapses postsynaptically immunoreactive for NCAM or PSA also showed immunoreactivity on their presynaptic membranes. NCAM180 was not detectable presynaptically in spine synapses. L1 could not be found in spine synapses either pre- or postsynaptically. Also, the extracellular matrix molecule tenascin-R was not detectable in synaptic clefts of all synapses tested, but was amply present between fasciculating axons, axon-astrocyte contact areas, and astrocytic gap junctions. Differences in expression of the membrane-bound adhesion molecules at both types of synapses may reflect the different mechanisms for induction and/or maintenance of synaptic plasticity.     

Immunoelectron microscopic localization of the neural recognition molecules L1, NCAM,and its isoform NCAM180, the NCAM‐associated polysialic acid,beta1 integrin and the extracellular matrix molecule tenascin‐R in synapses of the adult rat hippocampus

We have investigated the possibility that morphologically different excitatory glutamatergic synapses of the “trisynaptic circuit” in the adult rodent hippocampus, which display different types of long‐term potentiation (LTP), may express the immunoglobulin superfamily recognition molecules L1 and NCAM, the extracellular matrix molecule tenascin‐R, and the extracellular matrix receptor constituent beta1 integrin in a differential manner. The neural cell adhesion molecules L1, NCAM (all three major isoforms), NCAM180 (the largest major isoform with the longest cytoplasmic domain), beta1 integrin, polysialic acid (PSA) associated with NCAM, and tenascin‐R were localized by pre‐embedding immunostaining procedures in the CA3/CA4 region (mossy fiber synapses) and in the dentate gyrus (spine synapses) of the adult rat hippocampus. Synaptic membranes of mossy fiber synapses where LTP is expressed presynaptically did not show detectable levels of immunoreactivity for any of the molecules/epitopes studied. L1, NCAM, and PSA, but not NCAM180 or beta1 integrin, were detectable on axonal membranes of fasciculating mossy fibers. In contrast to mossy fiber synapses, spine synapses in the outer third of the molecular layer of the dentate gyrus, which display postsynaptic expression mechanisms of LTP, were both immunopositive and immunonegative for NCAM, NCAM180, beta1 integrin, and PSA. Those spine synapses postsynaptically immunoreactive for NCAM or PSA also showed immunoreactivity on their presynaptic membranes. NCAM180 was not detectable presynaptically in spine synapses. L1 could not be found in spine synapses either pre‐ or postsynaptically. Also, the extracellular matrix molecule tenascin‐R was not detectable in synaptic clefts of all synapses tested, but was amply present between fasciculating axons, axon‐astrocyte contact areas, and astrocytic gap junctions. Differences in expression of the membrane‐bound adhesion molecules at both types of synapses may reflect the different mechanisms for induction and/or maintenance of synaptic plasticity. © 2001 John Wiley & Sons, Inc. J Neurobiol 49: 142–158, 2001