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- Agnati, LF, et al.
(författare)
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Functional roles of three cues that provide nonsynaptic modes of communication in the brain: electromagnetic field, oxygen, and carbon dioxide
- 2018
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Ingår i: Journal of neurophysiology. - : American Physiological Society. - 1522-1598 .- 0022-3077. ; 119:1, s. 356-368
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Tidskriftsartikel (refereegranskat)abstract
- The integrative actions of the brain depend on the exchange of information among its computational elements. Hence, this phenomenon plays the key role in driving the complex dynamics of the central nervous system, in which true computations interact with noncomputational dynamical processes to generate brain representations of the body and of the body in the external world, and hence the finalistic behavior of the organism. In this context, it should be pointed out that, besides the intercellular interactions mediated by classical electrochemical signals, other types of interactions, namely, “cues” and “coercions,” also appear to be exploited by the system to achieve its function. The present review focuses mainly on cues present in the environment and on those produced by cells of the body, which “pervade” the brain and contribute to its dynamics. These cues can also be metabolic substrates, and, in most cases, they are of fundamental importance to brain function and the survival of the entire organism. Three of these highly pervasive cues will be analyzed in greater detail, namely, oxygen, carbon dioxide, and electromagnetic fields (EMF). Special emphasis will be placed on EMF, since several authors have suggested that these highly pervasive energy fluctuations may play an important role in the global integrative actions of the brain; hence, EMF signaling may transcend classical connectionist models of brain function. Thus the new concept of “broadcasted neuroconnectomics” has been introduced, which transcends the current connectomics view of the brain.
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| 3. |
- Agnati, LF, et al.
(författare)
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Role of iso-receptors in receptor-receptor interactions with a focus on dopamine iso-receptor complexes
- 2016
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Ingår i: Reviews in the neurosciences. - : Walter de Gruyter GmbH. - 2191-0200 .- 0334-1763. ; 27:1, s. 1-25
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Tidskriftsartikel (refereegranskat)abstract
- Intercellular and intracellular communication processes consist of signals and recognition/decoding apparatuses of these signals. In humans, the G protein-coupled receptor (GPCR) family represents the largest family of cell surface receptors. More than 30 years ago, it has been proposed that GPCR could form dimers or higher-order oligomers (receptor mosaics [RMs] at the plasma membrane level and receptor-receptor interactions [RRIs] have been proposed as a new integrative mechanism for chemical signals impinging on cell plasma membranes). The basic phenomena involved in RRIs are allostery and cooperativity of membrane receptors, and the present paper provides basic information concerning their relevance for the integrative functions of RMs. In this context, the possible role of iso-receptor RM is discussed (with a special focus on dopamine receptor subtypes and on some of the RMs they form with other dopamine iso-receptors), and it is proposed that two types of cooperativity, namely, homotropic and heterotropic cooperativity, could allow distinguishing two types of functionally different RMs. From a general point of view, the presence of iso-receptors and their topological organization within RMs allow the use of a reduced number of signals for the intercellular communication processes, since the target cells can recognize and decode the same signal in different ways. This theoretical aspect is further analyzed here by means of an analogy with artificial information systems. Thus, it is suggested that the ‘multiplexer’ and ‘demultiplexer’ concepts could, at least in part, model the role of RMs formed by iso-receptors in the information handling by the cell.
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| 5. |
- Agnati, LF, et al.
(författare)
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The multi-facet aspects of cell sentience and their relevance for the integrative brain actions: role of membrane protein energy landscape
- 2016
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Ingår i: Reviews in the neurosciences. - : Walter de Gruyter GmbH. - 2191-0200 .- 0334-1763. ; 27:4, s. 347-363
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Tidskriftsartikel (refereegranskat)abstract
- Several ion channels can be randomly and spontaneously in an open state, allowing the exchange of ion fluxes between extracellular and intracellular environments. We propose that the random changes in the state of ion channels could be also due to proteins exploring their energy landscapes. Indeed, proteins can modify their steric conformation under the effects of the physicochemical parameters of the environments with which they are in contact, namely, the extracellular, intramembrane and intracellular environments. In particular, it is proposed that the random walk of proteins in their energy landscape is towards attractors that can favor the open or close condition of the ion channels and/or intrinsic activity of G-protein-coupled receptors. The main aspect of the present proposal is that some relevant physicochemical parameters of the environments (e.g. molecular composition, temperature, electrical fields) with which some signaling-involved plasma membrane proteins are in contact alter their conformations. In turn, these changes can modify their information handling via a modulatory action on their random walk towards suitable attractors of their energy landscape. Thus, spontaneous and/or signal-triggered electrical activities of neurons occur that can have emergent properties capable of influencing the integrative actions of brain networks. Against this background, Cook’s hypothesis on ‘cell sentience’ is developed by proposing that physicochemical parameters of the environments with which the plasma-membrane proteins of complex cellular networks are in contact fulfill a fundamental role in their spontaneous and/or signal-triggered activity. Furthermore, it is proposed that a specialized organelle, the primary cilium, which is present in most cells (also neurons and astrocytes), could be of peculiar importance to pick up chemical signals such as ions and transmitters and to detect physical signals such as pressure waves, thermal gradients, and local field potentials.
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| 10. |
- Borroto-Escuela, DO, et al.
(författare)
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The role of transmitter diffusion and flow versus extracellular vesicles in volume transmission in the brain neural-glial networks
- 2015
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Ingår i: Philosophical transactions of the Royal Society of London. Series B, Biological sciences. - : The Royal Society. - 1471-2970. ; 370:1672
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Tidskriftsartikel (refereegranskat)abstract
- Two major types of intercellular communication are found in the central nervous system (CNS), namely wiring transmission (point-to-point communication, the prototype being synaptic transmission with axons and terminals) and volume transmission (VT; communication in the extracellular fluid and in the cerebrospinal fluid (CSF)) involving large numbers of cells in the CNS. Volume and synaptic transmission become integrated inter alia through the ability of their chemical signals to activate different types of receptor protomers in heteroreceptor complexes located synaptically or extrasynaptically in the plasma membrane. The demonstration of extracellular dopamine (DA) and serotonin (5-HT) fluorescence around the DA and 5-HT nerve cell bodies with the Falck–Hillarp formaldehyde fluorescence method after treatment with amphetamine and chlorimipramine, respectively, gave the first indications of the existence of VT in the brain, at least at the soma level. There exist different forms of VT. Early studies on VT only involved spread including diffusion and flow of soluble biological signals, especially transmitters and modulators, a communication called extrasynaptic (short distance) and long distance (paraaxonal and paravascular and CSF pathways) VT. Also, the extracellular vesicle type of VT was demonstrated. The exosomes (endosome-derived vesicles) appear to be the major vesicular carriers for VT but the larger microvesicles also participate. Both mainly originate at the soma–dendritic level. They can transfer lipids and proteins, including receptors, Rab GTPases, tetraspanins, cholesterol, sphingolipids and ceramide. Within them there are also subsets of mRNAs and non-coding regulatory microRNAs. At the soma–dendritic membrane, sets of dynamic postsynaptic heteroreceptor complexes (built up of different types of physically interacting receptors and proteins) involving inter alia G protein-coupled receptors including autoreceptors, ion channel receptors and receptor tyrosine kinases are hypothesized to be the molecular basis for learning and memory. At nerve terminals, the presynaptic heteroreceptor complexes are postulated to undergo plastic changes to maintain the pattern of multiple transmitter release reflecting the firing pattern to be learned by the heteroreceptor complexes in the postsynaptic membrane.
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