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More than 30 years have elapsed since the publication of the first reports of long-term potentiation by Bliss and Lomo (1973) and Bliss and Gardner-Medwin (1973). These two reports ushered in an exciting new era in which measurable persistent changes in synaptic strength were posited as substrates for learning and memory. Since that time, the study of long-term mechanisms of synaptic plasticity have arguably been one of the most intensely and perhaps the most rewarding fields of the neurosciences, casting important light on the nature of synaptic transmission and the events associated with the strengthening or weakening of synapses. Indeed, although once principally studied at excitatory glutamatergic synapses within the hippocampus and cortical formations, mechanisms of synaptic plasticity are observed at a myriad of synaptic connections throughout the mammalian central nervous system. Moreover, although many of these synapses share common mechanisms of plasticity, the last decade has seen an explosion in our understanding of plasticities peculiar to one synapse or another. This chapter does not attempt to cover all of these divergent mechanisms but instead focuses on those mechanisms of long-term potentiation (LTP) and depression (LTD) most commonly found within the hippocampal formation. A large portion of this review covers N-methyl-\fontsize77\selectfont D-aspartate-receptor-dependent LTP and LTD, the two most commonly studied forms of cortical plasticity; however, it also addresses plasticity mechanisms at other hippocampal synapses that have not enjoyed the same intensity of investigation but are worthy of attention. [ABSTRACT FROM AUTHOR]

Kainate receptors are glutamate-gated ion channels whose functional roles in the brain have been only poorly understood until recently. A picture has developed over the last decade of kainate receptors as subtle actors in neurotransmission; they modulate excitatory and inhibitory transmission and neuronal excitability and generate small but prolonged depolarizations at a subset of postsynaptic sites. This chapter reviews a variety of aspects of kainate receptor function, including their structure, biophysical function, and activities in (and out) of synapses in the mammalian brain. [ABSTRACT FROM AUTHOR]

α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMP ARs) are glutamate-gated ion channels. They are the neurotransmitter receptors that mediate the great majority of fast excitatory synaptic transmission in the mammalian brain and are found throughout the animal kingdom in organisms as diverse as rodents, honeybees, nematode worms, and humans. They are absolutely critical for brain function; for example, infusion of a selective AMPAR antagonist into the rat hippocampus in vivo completely silences excitatory transmission in that region (1). AMPARs are also required for adaptive changes in the brain, mediating the expression of forms of long-term and short-term synaptic plasticity that are believed to underlie learning and memory, development, and certain neurologic diseases (2-5). Thus, AMPARs play a central role in brain function, and consequently there is great interest in the development of novel therapies directed at modulating AMPAR function for treatment of neurologic disorders, such as Alzheimer disease and stroke. [ABSTRACT FROM AUTHOR]

Polyamines in naturally occurring compounds are biologically active molecules that do not display a great diversity but are very abundant in almost all organisms. Their functions comprise antibiotics, immunosuppressants, toxins, and many others. In most biologically active compounds the polyamine chain is coupled to other functionalities making the polyamine an excellent template for solid phase chemistry and combinatorial approaches. This review comprises common techniques for the synthesis of polyamines and polyamine derivatives on solid support. It includes the description of basic synthesis requirements such as of suitable resins, new linkers, reaction conditions for generation of biologically active polyamines and polyamines in natural products as well as the description of protection groups. Moreover, it will focus on the modular coupling of the amine building blocks using different synthesis strategies. Thus, the advantages of performing reactions on polymer-supported substrates in terms of avoiding side reactions and facilitating product/metal separation are highlighted. [ABSTRACT FROM AUTHOR]