Spatial Learning Activates Neural Cell Adhesion Molecule Polysialylation in a Corticohippocampal Pathway Within the Medial Temporal Lobe

O’Connell, Ann A.; Fox, Gerard B.; Barry, Thomas; Murphy, Keith J.; Fichera, Giacomo; Foley, Andrew; Kelly, John F.; Regan, Ciaran M.

doi:10.1046/j.1471-4159.1997.68062538.x

Cited by 72 publications

(55 citation statements)

References 22 publications

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“…phy Foley et al, 2003a,b). This timing is coherent with the role of PSA-NCAM in activity-induced synaptogenesis (Theodosis et al, 1999;Dityatev et al, 2004) and the time dynamics of synaptic changes that transiently occur in the DG during late stages of consolidation in other shock-related contextual tasks (O'Connell et al, 1997;O'Malley et al, 1998). (3) The increase was directly related to training and was not a mere activation induced by testing animals for retrieval.…”

Section: Discussionsupporting

confidence: 66%

Upregulation of Polysialylated Neural Cell Adhesion Molecule in the Dorsal Hippocampus after Contextual Fear Conditioning Is Involved in Long-Term Memory Formation

López-Fernández¹,

Montaron²,

Varea³

et al. 2007

J. Neurosci.

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The role of the hippocampus in pavlovian fear conditioning is controversial. Although lesion and pharmacological inactivation studies have suggested a key role for the dorsal hippocampus in contextual fear conditioning, the involvement of the ventral part is still uncertain. Likewise, the debate is open with regard to the putative implication of each hippocampal subdivision in fear conditioning to a discrete conditioned stimulus. We explored the potential existence of dissociations occurring in the dorsal versus ventral hippocampus at the cellular level while dealing with either contextual or cued fear conditioning and focused in a molecular "signature" linked to structural plasticity, the polysialylated form of the neural cell adhesion molecule (PSA-NCAM). We found an upregulation of PSA-NCAM expression in the dorsal (but not ventral) dentate gyrus at 24 h after contextual (but not tone) fear conditioning. Specific removal of PSA through microinfusion of the enzyme endoneuraminidase-N in the dorsal (but not ventral) hippocampus reduced freezing responses to the conditioned context. Therefore, we present evidence for a specific role of PSA-NCAM in the dorsal hippocampus in the plasticity processes occurring during consolidation of the context representation after "standard" contextual fear conditioning. Interestingly, we also found that exposing animals just to the context induced an activation of PSA-NCAM in both dorsal and ventral dentate gyrus. Altogether, these findings highlighting the distinctive occurrence of these neuroplastic processes in the dorsal hippocampus during the standard contextual fear-conditioning task enlighten the ongoing debate about the involvement of these hippocampal subdivisions in pavlovian fear conditioning.

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Section: Discussionsupporting

confidence: 66%

Upregulation of Polysialylated Neural Cell Adhesion Molecule in the Dorsal Hippocampus after Contextual Fear Conditioning Is Involved in Long-Term Memory Formation

López-Fernández¹,

Montaron²,

Varea³

et al. 2007

J. Neurosci.

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“…For instance, excess of PSA has been shown to interfere with induction of LTP (Muller et al, 2000; present study) and brain-derived neurotrophic factor signaling (Muller et al, 2000). PSA and PSA-NCAM-Fc may also function as competitive antagonists abolishing PSA-NCAMdriven synaptogenesis at postsynaptic sites at which PSA-NCAM expression is upregulated by a learning event (Fox et al, 1995;Murphy et al, 1996;O'Connell et al, 1997;Sandi et al, 2003). Different molecular mechanisms may also be involved during the consolidation phase of fear conditioning, because posttraining injection of PSA-NCAM-Fc, but not PSA, impairs consolidation of contextual memory.…”

Section: Discussionmentioning

confidence: 73%

“…Previous experiments using injection of NCAM antibodies and a synthetic peptide (C3d) that affects homophilic interaction with NCAM revealed the existence of a short post-training time window in which consolidation can be disrupted via alterations in NCAM functions (Doyle et al, 1992;Cambon et al, 2003). In addition, during memory consolidation, a transient, time-dependent learning-induced increase in expression and polysialylation of NCAM has been observed in the hippocampus, and entorhinal and perirhinal cortices throughout different behavioral paradigms and species (Doyle et al, 1992;Scholey et al, 1993;Fox et al, 1995;Arami et al, 1996;Murphy et al, 1996;O'Connell et al, 1997;Sandi et al, 2003). Taking these data together with our results, there is a time window at 6 h post-training that depends on PSA-NCAM, rather than on the individual components, PSA or NCAM.…”

Section: Discussionmentioning

confidence: 99%

Polysialylated Neural Cell Adhesion Molecule Is Involved in Induction of Long-Term Potentiation and Memory Acquisition and Consolidation in a Fear-Conditioning Paradigm

Senkov¹,

Sun²,

Weinhold³

et al. 2006

J. Neurosci.

132

104

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Polysialic acid (PSA) regulates functions of the neural cell adhesion molecule (NCAM) during development and in neuroplasticity in the adult; the underlying mechanisms at different phases of learning and memory consolidation are, however, unknown. To investigate the contributions of PSA versus the extracellular domain of the NCAM glycoprotein backbone to synaptic plasticity, we applied NCAM, PSA-NCAM, and PSA to acute slices of the hippocampal CA1 region of NCAM-deficient mice and measured their effects on long-term potentiation (LTP). Remarkably, only PSA and PSA-NCAM, but not NCAM restored normal LTP. Application of these molecules to the dorsal hippocampus of wild-type mice showed that PSA-NCAM and PSA, but not NCAM, injected before fear conditioning, impaired formation of hippocampus-dependent contextual memory. Consolidation of contextual memory was affected by PSA-NCAM only when injected during its late, but not early phases. None of the tested compounds disturbed extrahippocampal-cued memory. Mice lacking the polysialyltransferase (ST8SialV/PST) responsible for attachment of PSA to NCAM in adulthood showed a mild deficit only in hippocampal contextual learning, when compared with NCAM-deficient mice that were disturbed in both contextual and cued memories. Contextual and tone memory in NCAM-deficient mice could be partially restored by injection of PSA-NCAM, but not of NCAM, into the hippocampus, suggesting that the impact of PSA-NCAM in synaptic plasticity and learning is not mediated by modulation of NCAM–NCAM homophilic interactions. In conclusion, our data support the view that polysialylated NCAM is involved in both formation and late consolidation of contextual memory.

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“…Changes in PSA expression associated with learning and memory consolidation have been observed in the dentate gyrus of the hippocampus (Doyle, Nolan, Bell, & Regan, 1992a;Merino, Cordero, & Sandi, 2000;Murphy, O'Connell, & Regan, 1996;Murphy & Regan, 1998;Sandi et al, 2003), in subregions of the amygdala complex (Markram, Lopez Fernandez, Abrous, & Sandi, 2007b), and the entrohinal/perihinal cortices (Fox et al, 2000;O'Connell et al, 1997). Enzymatic removal of PSA, by PSA-specific endoneuraminidase (endo-N), results in complete loss of LTP and LTD induction in vitro (Muller et al, 1996), and in vivo to impaired learning and memory formation (Becker et al, 1996;Lopez-Fernandez et al, 2007;Venero et al, 2006).…”

Section: Ncam Polysialylation (Psa-ncam)mentioning

confidence: 99%

Learning under stress: A role for the neural cell adhesion molecule NCAM

Bisaz

Conboy

Sandi

2009

Neurobiology of Learning and Memory

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a b s t r a c tStress is known to be a potent modulator of brain function and cognition. While prolonged and/or excessive stress generally exerts negative effects on learning and memory processes, acute stress can have differential effects on memory function depending on a number of factors (such as stress duration, stress intensity, timing and the source of the stress, as well as the learning type under study). Here, we have focused on the effects of 'acute' stress, and examined the literature attending to whether the ''source of stress" is 'intrinsic' (i.e., when stress is originated by the cognitive task) or 'extrinsic' (i.e., when stress is induced by elements not related to the cognitive task). We have questioned here whether the neural cell adhesion molecule of the immunoglobulin superfamily (NCAM) contributes to the neurobiological mechanisms that translate the effects of these two different stress sources into the different behavioral and cognitive outcomes. NCAM is a cell adhesion macromolecule known to play a critical role in development and plasticity of the nervous system. NCAM and its post-translational modified form PSA-NCAM are critically involved in mechanisms of learning and memory and their expression levels are known to be highly susceptible to modulation by stress. Whereas available data are insufficient to conclude as to whether NCAM mediates extrinsic stress effects on learning and memory processes, we present systematic evidence supporting a key mediating role for both NCAM and PSA-NCAM in the facilitation of memory consolidation induced by intrinsic stress. Furthermore, NCAM is suggested to participate in some of the bidirectional effects of stress on memory processes, with its enhanced synaptic expression involved in facilitating stress actions while its reduced expression being related to impairing effects of stress on memory function.

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Spatial Learning Activates Neural Cell Adhesion Molecule Polysialylation in a Corticohippocampal Pathway Within the Medial Temporal Lobe

Cited by 72 publications

References 22 publications

Upregulation of Polysialylated Neural Cell Adhesion Molecule in the Dorsal Hippocampus after Contextual Fear Conditioning Is Involved in Long-Term Memory Formation

Upregulation of Polysialylated Neural Cell Adhesion Molecule in the Dorsal Hippocampus after Contextual Fear Conditioning Is Involved in Long-Term Memory Formation

Polysialylated Neural Cell Adhesion Molecule Is Involved in Induction of Long-Term Potentiation and Memory Acquisition and Consolidation in a Fear-Conditioning Paradigm

Learning under stress: A role for the neural cell adhesion molecule NCAM

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