Neuroscience
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In this review we will discuss the effect of two neuromodulatory transmitters, acetylcholine (ACh) and adenosine, on the synaptic release probability and short-term synaptic plasticity. ACh and adenosine differ fundamentally in the way they are released into the extracellular space. ⋯ In contrast, adenosine is released from both neurons and glia via nucleoside transporters or diffusion over the cell membrane in a non-vesicular, non-synaptic fashion; its receptors are exclusively G-protein coupled receptors. We show that ACh and adenosine effects are highly specific for an identified synaptic connection and depend mostly on the presynaptic but also on the postsynaptic receptor type and discuss the functional implications of these differences.
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Variations of synaptic strength are thought to underlie forms of learning and can functionally reshape neural circuits. Metabotropic glutamate receptors play key roles in regulating the strength of chemical synapses. ⋯ Activity-driven interactions between metabotropic glutamate receptors and neuronal gap junctions can lead to long-term changes in the strength of electrical synapses. Further, the regulatory action of metabotropic glutamate receptors on neuronal gap junctions is not restricted to adulthood but is also of critical relevance during brain development and contributes to the pathological mechanisms that follow brain injury.
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The brain is inherently asymmetrical. How that attribute, manifest both structurally (volumetric, cytological, molecular) as well as functionally, relates to cognitive function, is not fully understood. Since the early descriptions of Paul Broca and Marc Dax it has been known that the processing of language in the brain is fundamentally asymmetrical. ⋯ Indeed, in terms of cognitive function, successful aging is often associated with a reduction of asymmetrical activity. The goal of this review is to survey and critically appraise the current literature addressing brain laterality, both morphological and functional, with particular emphasis on the asymmetrical plasticity associated with environmental factors and training. The plastic recruitment of contralateral areas associated with aging and unilateral lesions will be discussed in the context of the loss of asymmetry as a compensatory mechanism, and specific instances of maladaptive plasticity will be explored.
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Besides their primary function mediating the repolarization phase of action potentials, potassium channels exquisitely and ubiquitously regulate the resting membrane potential of neurons and therefore have a key role establishing their intrinsic excitability. This group of proteins is composed of a very diverse collection of voltage-dependent and -independent ion channels, whose specific distribution is finely tuned at the level of the synapse. Both at the presynaptic and postsynaptic membranes, different types of potassium channels are subjected to modulation by second messenger signaling cascades triggered by metabotropic receptors, which in this way serve as a link between neurotransmitter actions and changes in the neuron membrane excitability. ⋯ On the other hand, these channels maintain the presynaptic membrane potential under control, therefore influencing the probability of neurotransmitter release underlying different forms of short-term plasticity. In the present review, we examine in detail the role of metabotropic receptors translating their activation by different neurotransmitters into a final effect modulating several types of potassium channels. Furthermore, we evaluate the consequences that this interplay has on the induction and maintenance of different forms of synaptic plasticity.
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NMDA receptors (NMDARs) play a critical role in excitatory synaptic transmission, plasticity and in several forms of learning and memory. In addition, NMDAR dysfunction is believed to underlie a number of neuropsychiatric conditions. ⋯ Ligands that bind to GPCRs, such as neurotransmitters and neuromodulators, activate intracellular pathways that modulate NMDAR expression, subcellular localization and/or functional properties in a short- or a long-term manner across many synapses throughout the central nervous system. In this review article we summarize current knowledge on the molecular and cellular mechanisms underlying NMDAR modulation by GPCRs, and we discuss the implications of this modulation spanning from synaptic transmission and plasticity to circuit function and brain disease.