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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Mismatch negativity (MMN) is an electrophysiological signature that occurs in response to unexpected stimuli. It is often referred to as a measure of memory-based change detection, because the elicitation of a prediction error response relies on the formation of a prediction, which in turn, is dependent upon intact memory of previous auditory stimulation. ⋯ The most prominent pharmacological finding for MMN strengthens the link between MMN and synaptic plasticity, as glutamate N-methyl-d-aspartate receptor (NMDA-R) antagonists reduce the MMN response. However, recent data has begun to demonstrate that the link between NMDA-R function and MMN is not as clear as once thought, with low dose and low affinity NMDA-R antagonists observed to facilitate MMN.
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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.