Elsevier

Pharmacological Research

Volume 50, Issue 2, August 2004, Pages 111-122
Pharmacological Research

Emerging targets for the pharmacology of learning and memory

https://doi.org/10.1016/j.phrs.2004.01.003Get rights and content

Abstract

Learning and memory are dynamic processes associated with modifications in morphology, biochemistry and physiology of the nervous system, that can be analysed at different levels of biological organization. Within this context, changes correlated with cognitive processes are identifiable at distinct cellular and molecular loci of the nervous system. Synaptic plasticity represents an experience-dependent alteration of neuronal properties that subserve learning and memory, and for which a neuronal network can be considered as a candidate for being part of an engram. Multiple molecular systems at various levels of the signal transduction cascade, such as those involving receptors, second messengers and gene expression, may be linked to synaptic remodelling during cognitive processes. After a brief overview of the various facets of memory and the higher levels of cerebral organization (with special attention to the hippocampus), this review is devoted to the presentation of some novel potential therapeutic targets within the signal transduction cascade that might be considered for rational pharmacological intervention to improve learning and memory in both diseased and healthy individuals.

Section snippets

The various facets of memory

The majority of organisms exhibit cognitive functions that we identify as learning and memory. Studies of animal models and patients with circumscribed memory impairment have contributed to our understanding of cognitive processes, suggesting that memory is not a single entity, but there are different kinds of memory involving distinct neuronal systems in the brain [1]. The most persistent form of information storage is genetic, one that is constituted by innate, prefixed responses provided to

In search of a memory site

As mentioned, memory can be divided into various components and forms on the basis of the content (i.e. semantic or episodic), the type (i.e. associative), the level of processing (i.e. encoding, retrieval) and the duration (i.e. short-term and long-term) [11]. But how can we define learning and memory? Learning can be considered a process that allows us to acquire new information about the world and “which manifests itself by adaptative changes in individual behaviour as a result of

The role of the hippocampus in cognitive processes

Fundamental information on the role of a specific area of the brain in learning and memory derived from the most studied amnesic patient, H.M., who underwent bilateral removal of his medial temporal lobe that includes the hippocampus and the amygdala. The operation alleviated H.M.’s epilepsy, but also resulted in anterograde amnesia and partial loss of memory for events which occurred in the decade preceding the operation. Memory of more remote events was not affected; working memory did not

Learning and memory as multilevel phenomena: a foreshortening on cellular and molecular mechanisms of cognitive processes

In view of previous considerations, learning and memory can be analysed at different levels of biological organization. After a brief overview regarding the different forms of memory, and a few considerations on some circuits involved (in particular the hippocampus), the next part of this review will deal with some cellular and molecular levels of cognitive processes. Because learning and memory are dynamic processes, although not instantaneous changes, Burgoyne and Rose proposed that any cell,

New emerging targets for pharmacologic therapy of memory impairment

In this context, we will now consider some of the multiple possibilities of intervention to affect signal transduction cascades, with the aim to enlighten new pharmacological approaches to address memory deficits. In addition to a brief mention of glutamate, the review will be focused on some of the emerging extracellular and intracellular signals involved in memory trace formation such as angiotensin, carbonic anhydrase and APP. Attention will also be paid to the control of gene expression in

Conclusions

One of the most important efforts of the last decade in research is to gain a better insight on the mechanisms involved in cognitive function. Understanding the biochemical basis of learning and memory processes can certainly help to elucidate how to restore normal brain functioning. For years pharmacological research has been looking for novel routes and therapeutic approaches to address the problem of memory impairment. The biochemical entities participating in signal transduction cascades

Acknowledgements

The authors wish to thank Madelon Cook (Blanchette Rockefeller Neurosciences Institute, Rockville, MD, USA) for her help in carefully reviewing the text.

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