T t

Central nucleus no effect

Basolateral nucleus Inhibition of glucocortrcoid-induced memory enhancement

Figure 5. Role of amygdala nuclei in the memory-facilitating effect of glucocorticoids. Cartoon showing neural circuits involved in the communication among different amygdala nuclei. When the central nucleus is lesioned in rats before being exposed to a training session in the passive avoidance task, the enhancement ofmemory induced by a posttraining glucocorticoid injection is preserved. However, when it is the basolateral nucleus which is lesioned, the facilitation of memory induced by glucocorticoids is prevented. Therefore, the basolateral nucleus has been proposed to play a critical role on the memory-facilitating effects of glucocorticoids. Based on data taken from ref. 55.

biochemical experiments showed that the intracerebral injection of a corticosterone dose that facilitated the storage of the avoidance response, enhanced protein fucosylation in a brain region largely implicated in learning and memory in the chick.70 Subsequent psychopharma-cological studies showed that the administration of the fucosyl-glycoprotein synthesis inhibitor, 2-deoxygalactose (2-DG), prevented the facilitating effect of corticosterone on retention when injected 5.5 — 7.5 h posttraining, but was ineffective if injected at earlier or later time points,65 therefore implicating glycoprotein fucosylation in the cognitive actions of the steroid. Interestingly, studies performed in rats also showed that corticosterone administration [at a dose that induces circulating stress levels of this steroid and facilitates consolidation of water maze learning (see above)] resulted in decreased glycoprotein expression in the hippocampus when evaluated 3 h post-injection, an effect which was suggested to be related to synaptic restructuring mechanisms.79

Among the different synaptic membrane glycoproteins, the cell adhesion molecules (CAMs) of the immunoglobulin superfamily (including the neural CAM -NCAM- and L1) have received particular attention in the search for the cellular and molecular mechanism of memory (see Fig. 6 and Regan, this book). CAMs are cell surface macromolecules that participate in target recognition and synapse stabilisation.46 They have been largely implicated in cell-cell interactions during development of the nervous system16 and in activity-dependent synaptic plasticity in adulthood,17, 6 including the synaptic changes underlying learning and memory

Figure 6. Schematic representation of the cell adhesion molecules of the immunoglobulin superfamily, NCAM and L1. These molecules are formed by five immunoglobulin domains and several fibronectin domains. NCAM is expressed in several isoforms which differ in their molecular weights and mode of attachment to the cytoplasmic membrane.

Figure 6. Schematic representation of the cell adhesion molecules of the immunoglobulin superfamily, NCAM and L1. These molecules are formed by five immunoglobulin domains and several fibronectin domains. NCAM is expressed in several isoforms which differ in their molecular weights and mode of attachment to the cytoplasmic membrane.

processes.75 Furthermore, the post-translational modification of NCAM that consists in the addition of a-2,8-linked polysialic acid (PSA) homopolymers to its fifth immunoglobulin-like domain, by attenuating interactions mediated by NCAM and other related molecules,61 provides another mechanism for structural plasticity. In fact, PSA-NCAM has also been implicated in memory formation15,19,47 and synaptic plasticity.2,45

Interestingly, these CAMs seem to be implicated in corticosteroid actions in cognitive processes. Thus, corticosterone facilitation of memory formation in the day-old chick was shown to be inhibited by intracerebral administration of NCAM antibodies 5.5 h posttraining.70 In rats, an acute corticosterone injection, although not affecting NCAM levels in the hippocampus, significantly enhanced NCAM expression in frontal cortical areas when evaluated 8 and 24 h post-injection.63

Interestingly, different effects were found when rats were submitted to a training experience involving different stressor intensities (and, as noted above, inducing different posttraining corticosterone levels), as shown for the contextual fear conditioning paradigm. As opposed to the lack of effect induced by the single injection of corticosterone in the hippocampus, rats trained in this fear conditioning task (at either 0.2, 0.4, or 1 mA shock intensity) showed a marked regulation of hippocampal CAMs which was dependent upon time and stressor intensity.41 At 12 h post-training, conditioned animals displayed reduced NCAM, but increased L1, expression. The group trained at the highest shock intensity (1 mA) also presented decreased PSA-NCAM expression. However, at 24 h posttraining, the 1 mA group exhibited increased NCAM and L1 expression, but decreased expression of PSA-NCAM levels. The pattern of CAMs expression found in the 1 mA group (which is the one that shows higher posttraining corticosterone levels and develops the stronger and longer lasting levels of fear conditioning) supports the view that, after a first phase of synaptic de-adherence during consolidation, NCAM and L1 might participate in the stabilization of selected synapses underlying the establishment of long-term memory for contextual fear conditioning. They also suggest that glucocorticoids might play a role in the observed regulation of CAMs.

Was this article helpful?

0 0
Unraveling Alzheimers Disease

Unraveling Alzheimers Disease

I leave absolutely nothing out! Everything that I learned about Alzheimer’s I share with you. This is the most comprehensive report on Alzheimer’s you will ever read. No stone is left unturned in this comprehensive report.

Get My Free Ebook


Post a comment