Neuroscience
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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.
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Extensive research over the past decades has characterized multiple forms of synaptic plasticity, identifying them as key processes that allow the brain to operate in a dynamic manner. Within the wide variety of synaptic plasticity modulators, kainate receptors are receiving increasing attention, given their diversity of signaling mechanisms and cellular expression profile. Here, we summarize the experimental evidence about the involvement of kainate receptor signaling in the regulation of short- and long-term plasticity, from the perspective of the regulation of neurotransmitter release. In light of this evidence, we propose that kainate receptors may be considered homeostatic modulators of neurotransmitter release, able to bidirectionally regulate plasticity depending on the functional history of the synapse.
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Acetylcholine acting via metabotropic receptors plays a key role in learning and memory by regulating synaptic plasticity and circuit activity. However, a recent overall view of the effects of muscarinic acetylcholine receptors (mAChRs) on excitatory and inhibitory long-term synaptic plasticity and on circuit activity is lacking. This review focusses on specific aspects of the regulation of synaptic plasticity and circuit activity by mAChRs in the hippocampus and cortex. ⋯ This iLTD is caused by an endocannabinoid-mediated presynaptic inhibition that reduces the GABA release probability at the terminals of inhibitory interneurons. This bidirectional long-term plasticity of inhibition may dynamically regulate the excitatory/inhibitory balance depending on the quiescent or active state of the postsynaptic pyramidal neurons. Therefore, acetylcholine can induce varied effects on neuronal activity and circuit behavior that can enhance sensory detection and processing through the modification of circuit activity leading to learning, memory and behavior.
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Long-term changes in synaptic transmission between neurons in the brain are considered the cellular basis of learning and memory. Over the last few decades, many studies have revealed that the precise order and timing of activity between pre- and post-synaptic cells ("spike-timing-dependent plasticity; STDP") is crucial for the sign and magnitude of long-term changes at many central synapses. Acetylcholine (ACh) via the recruitment of diverse muscarinic receptors is known to influence STDP in a variety of ways, enabling flexibility and adaptability in brain network activity during complex behaviors. In this review, we will summarize and discuss different mechanistic aspects of muscarinic modulation of timing-dependent plasticity at both excitatory and inhibitory synapses in the hippocampus to shape learning and memory.