Neuroscience
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The space of possible neural models is enormous and under-explored. Single cell computational neuroscience models account for a range of dynamical properties of membrane potential, but typically do not address network function. In contrast, most models focused on network function address the dimensions of excitatory weight matrices and firing thresholds without addressing the complexities of metabotropic receptor effects on intrinsic properties. ⋯ Possible frameworks include maps of parameter spaces, or efforts to categorize the fundamental elements and molecules of neural circuit function. Here we review dimensions that are under-explored in network models that include the metabotropic modulation of synaptic plasticity and presynaptic inhibition, spike frequency adaptation due to calcium-dependent potassium currents, and afterdepolarization due to calcium-sensitive non-specific cation currents and hyperpolarization activated cation currents. Neuroscience research should more effectively explore possible functional models incorporating under-explored dimensions of neural function.
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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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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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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.