Memory Consolidation Induces a Transient and Time‐Dependent Increase in the Frequency of Neural Cell Adhesion Molecule Polysialylated Cells in the Adult Rat Hippocampus

Abstract

Animals trained in a passive avoidance task exhibit a transient time‐dependent increase in hippocampal neural cell adhesion molecule (NCAM) polysialylation at 12–24 h following the initial learning trial. Using immunocytochemical techniques with a monoclonal antibody that specifically recognises NCAM‐polysialic acid homopolymers, a distinct population of granule‐like cells, at the border of the granule cell layer and the hilus in the dentate gyrus of the adult rat hippocampus, has been demonstrated to exhibit time‐dependent change in frequency at 10–12 h following the initial learning of a one‐trial, step‐through, passive avoidance response. These changes were paradigm specific as they failed to occur in those animals rendered amnesic with scopolamine. These polysialylated dentate neurons are not de novo granule cell precursors as administration of 5‐bromo‐2′‐deoxyuridine every 2 h from the point of learning to the 12‐h posttraining time showed no significant difference between trained and passive animals in the small number of heterogeneously distributed, labelled cells. These findings directly identify a morphological substrate of memory, implied by previous correlative and interventive studies on NCAM function.

Chronic Exposure of Rats to Cognition Enhancing Drugs Produces a Neuroplastic Response Identical to that Obtained by Complex Environment Rearing

“…We evaluated this possibility by determining the magnitude of the learning-induced transient activation of NCAM PSA expression seen 12 h following training in both passive avoidance and water maze paradigms. Vehicle-treated animals exhibited learning-induced NCAM PSA activation following both tasks, the magnitude of which matched those observed previously (Fox et al, 1995;Murphy et al, 1996). Independent of task, animals receiving chronic nefiracetam, tacrine, or deprenyl exhibited no significant difference in the 12 h post-training frequency of NCAM PSA positive neurons as compared to the vehicle-treated control (Figure 4).…”

“…As the frequency of the dentate polysialylated neurons declines markedly with age in both rodent and human populations (Fox et al, 1995;Abrous et al, 1997;Ní Dhúill et al, 1999), the effects of a chronic drug regimen or a complex environment may relate to an attenuation in the decline of this cell population. Indeed, polysialylated cell frequency declines earlier in animals reared in social groups as compared to a complex environment (unpublished observations).…”

“…On postnatal day 80, animals were trained in a one-trial, step-through, light-dark passive avoidance paradigm (Fox et al, 1995). The smaller, illuminated compartment was separated from a larger compartment by a shutter that contained a small entrance.…”

“…Glycosylation of NCAM with extended chains of a2,8-linked polysialic acid (PSA) is also necessary for memory consolidation as their cleavage with endoneuraminidase prevents LTP and spatial learning (Becker et al, 1996;Muller et al, 1996;Kleene and Schachner, 2004). Within the hippocampus, a transient increase in polysialylation of neurons located at the dentate infragranular zone at 10-12 h following learning is necessary for memory consolidation (Fox et al, 1995;Murphy et al, 1996;Foley et al, 2003;Sandi et al, 2003). This neuroplastic mechanism is required for dendritic remodelling (Nothias et al, 1997;Hoyk et al, 2001) and is likely to be an important factor in the elaboration and integration of circuitry associated with the consolidation of novel behavioral repertoires (Wang et al, 2000).…”

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

“…Polysialylation of NCAMs has been implicated in hippocampus-dependent memory storage (Fox et al, 1995;Foley et al, 2003;Florian et al, 2006;Venero et al, 2006;Lopez-Fernandez et al, 2007;Markram et al, 2007). Long-term potentiation (LTP) and long-term depression (LTD) are widely accepted models of plasticity involved in memory processes.…”