Roles of Presynaptic NMDA Receptors in Neurotransmission and Plasticity

Presynaptic NMDA receptors (preNMDARs) play pivotal roles in excitatory neurotransmission and synaptic plasticity. They facilitate presynaptic neurotransmitter release and modulate mechanisms controlling synaptic maturation and plasticity during formative periods of brain development. There is an increasing understanding of the roles of preNMDARs in experience-dependent synaptic and circuit-specific computation. In this review, we summarize the latest understanding of compartment-specific expression and function of preNMDARs, and how they contribute to synapse-specific and circuit-level information processing

Modeling the formation process of grouping stimuli sets through cortical columns and microcircuits to feature neurons

A computational model of a self-structuring neuronal net is presented in which repetitively applied pattern sets induce the formation of cortical columns and microcircuits which decode distinct patterns after a learning phase. In a case study, it is demonstrated how specific neurons in a feature classifier layer become orientation selective if they receive bar patterns of different slopes from an input layer. The input layer is mapped and intertwined by self-evolving neuronal microcircuits to the feature classifier layer. In this topical overview, several models are discussed which indicate that the net formation converges in its functionality to a mathematical transform which maps the input pattern space to a feature representing output space. The self-learning of the mathematical transform is discussed and its implications are interpreted. Model assumptions are deduced which serve as a guide to apply model derived repetitive stimuli pattern sets to in vitro cultures of neuron ensembles to condition them to learn and execute a mathematical transform

Astrocytes: Orchestrating synaptic plasticity?

Synaptic plasticity is the capacity of a preexisting connection between two neurons to change in strength as a function of neural activity. Because synaptic plasticity is the major candidate mechanism for learning and memory, the elucidation of its constituting mechanisms is of crucial importance in many aspects of normal and pathological brain function. In particular, a prominent aspect that remains debated is how the plasticity mechanisms, that encompass a broad spectrum of temporal and spatial scales, come to play together in a concerted fashion. Here we review and discuss evidence that pinpoints to a possible non-neuronal, glial candidate for such orchestration: the regulation of synaptic plasticity by astrocytes

Astrocytes: orchestrating synaptic plasticity?

Synaptic plasticity is the capacity of a preexisting connection between two neurons to change in strength as a function of neural activity. Because synaptic plasticity is the major candidate mechanism for learning and memory, the elucidation of its constituting mechanisms is of crucial importance in many aspects of normal and pathological brain function. In particular, a prominent aspect that remains debated is how the plasticity mechanisms, that encompass a broad spectrum of temporal and spatial scales, come to play together in a concerted fashion. Here we review and discuss evidence that pinpoints to a possible non-neuronal, glial candidate for such orchestration: the regulation of synaptic plasticity by astrocytes.Comment: 63 pages, 4 figure

Parallel computing for brain simulation

[Abstract] Background: The human brain is the most complex system in the known universe, it is therefore one of the greatest mysteries. It provides human beings with extraordinary abilities. However, until now it has not been understood yet how and why most of these abilities are produced. Aims: For decades, researchers have been trying to make computers reproduce these abilities, focusing on both understanding the nervous system and, on processing data in a more efficient way than before. Their aim is to make computers process information similarly to the brain. Important technological developments and vast multidisciplinary projects have allowed creating the first simulation with a number of neurons similar to that of a human brain. Conclusion: This paper presents an up-to-date review about the main research projects that are trying to simulate and/or emulate the human brain. They employ different types of computational models using parallel computing: digital models, analog models and hybrid models. This review includes the current applications of these works, as well as future trends. It is focused on various works that look for advanced progress in Neuroscience and still others which seek new discoveries in Computer Science (neuromorphic hardware, machine learning techniques). Their most outstanding characteristics are summarized and the latest advances and future plans are presented. In addition, this review points out the importance of considering not only neurons: Computational models of the brain should also include glial cells, given the proven importance of astrocytes in information processing.Galicia. Consellería de Cultura, Educación e Ordenación Universitaria; GRC2014/049Galicia. Consellería de Cultura, Educación e Ordenación Universitaria; R2014/039Instituto de Salud Carlos III; PI13/0028

Astrocyte–Neuron Networks: A Multilane Highway of Signaling for Homeostatic Brain Function

Research on glial cells over the past 30 years has confirmed the critical role of astrocytes in pathophysiological brain states. However, most of our knowledge about astrocyte physiology and of the interactions between astrocytes and neurons is based on the premises that astrocytes constitute a homogeneous cell type, without considering the particular properties of the circuits or brain nuclei in which the astrocytes are located. Therefore, we argue that more-sophisticated experiments are required to elucidate the specific features of astrocytes in different brain regions, and even within different layers of a particular circuit. Thus, in addition to considering the diverse mechanisms used by astrocytes to communicate with neurons and synaptic partners, it is necessary to take into account the cellular heterogeneity that likely contributes to the outcomes of astrocyte–neuron signaling. In this review article, we briefly summarize the current data regarding the anatomical, molecular and functional properties of astrocyte–neuron communication, as well as the heterogeneity within this communication

Ο ρόλος των αστροκυττάρων στις διεργασίες της μάθησης και της μνήμης

Διπλωματική εργασία--Πανεπιστήμιο Μακεδονίας, Θεσσαλονίκη, 2019Ο νευρικός ιστός αποτελείται από νευρικά κύτταρα (νευρώνες) και νευρογλοιακά κύτταρα (νευρογλοία). Τα νευρογλοιακά κύτταρα παρεμβάλλονται μεταξύ των νευρώνων, εκτός από τις θέσεις των συνάψεων. Ενώ γνωρίζουμε αρκετά πράγματα για τους νευρώνες, ο ρόλος των νευρογλοιακών κυττάρων στις λειτουργίες του εγκεφάλου δεν έχει αναλυθεί επαρκώς. Ωστόσο, τις τελευταίες δεκαετίες, ερευνητικά δεδομένα καταδεικνύουν τον καθοριστικό ρόλο τους στις διεργασίες της μάθησης και της μνήμης, μέσω της επιρροής που ασκούν στη συναπτική διαβίβαση και στον σχηματισμό συνάψεων. Στόχος της διπλωματικής αυτής εργασίας είναι: α) Η περιγραφή της δομής και της λειτουργίας των νευρογλοιακών κυττάρων και η ανάδειξη του πρωταγωνιστικού ρόλου τουςστο ΚΝΣ, και β) Η διερεύνηση του ρόλου των αστροκυττάρων στις λειτουργίες της μάθησης και της μνήμης. Τα σύγχρονα ευρήματα υποδηλώνουν ότι: 1. Τα αστροκύτταρα επηρεάζουν την επαγωγή της LTP/LTD, διευκολύνοντας ή παρεμποδίζοντας την εκτέλεση γνωστικών ή μνημονικών λειτουργιών. 2. Η απώλεια δικτύων αστροκυττάρων σε συγκεκριμένες περιοχές στον ανθρώπινο εγκέφαλο μπορεί να οδηγήσει σε γνωστικές και μνημονικές δυσλειτουργίες. Και 3. Το συγκύτιο των αστροκυττάρων είναι δυνατόν να συμμετέχει στην αποθήκευση των αναμνήσεων, μέσω της δραστηριότητας των ιοντικών διαύλων των αστροκυττάρων.The neural tissue is composed of nerve cells (neurons) and neuroglial cells (neuroglia). Neuroglial cells surround neurons, with the exception of synapses. While we know quite a few things about neurons, the role of glial cells in brain functioning has not been sufficiently analyzed. However, over the last few decades, a number of research’s findings show that astroglial cells play a key role in synaptic transmission and formation of synapses; consequently, learning and memory processes are directly influenced. The objective of this diploma thesis are: A) to make a thorough presentation of the structure and function of neuroglial cells, with emphasis to astrocytes b) to review the role of astrocytes in learning and memory. Modern findings suggest that: 1. Astrocytes affect the induction of LTP / LTD by facilitating or inhibiting the performance of cognitive or memory functions; 2. Loss of astrocyte networks in specific areas in the human brain can lead to cognitive and memory disorders and 3. The astrocytes’ syncutium can participate in the storage of memories through the activity of the astrocytic ion channels

Analysis of network models with neuron-astrocyte interactions

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The Role of System XC- in Cognition: The Importance of Neuron-Astrocyte Signaling

The biological basis of human intelligence is largely a mystery, but likely required evolutionary adaptations to achieve the information processing capacity needed to expand the complexity of cognition among species. The link between evolutionary expansion of signaling complexity in the brain and cognition has largely focused on neuronal mechanisms, in part because information processing has historically been attributed to these cells. However, astrocytes are emerging as a second type of brain cell that is capable of processing information due to their capacity to release glutamate and, thereby, regulate neural circuits. Hence, a modern question is whether astrocytes contributed to the signaling complexity required for sophisticated forms of cognition. The glutamate release mechanism system xc- (Sxc) is the ideal mechanism to investigate this question because it is evolutionarily novel to vertebrate species and it is expressed by astrocytes. The central hypothesis tested herein is that Sxc increased the complexity of glutamate signaling and is required for behavior requiring complex cognition. To test, a genetically modified rat with Sxc activity eliminated was generated (MSxc rats). Phenotyping revealed that loss of Sxc activity produced changes in behavior that reflect diminished cognition or top-down processing including impaired reversal learning, set-shifting, and attentional allocation. Remarkably, loss of Sxc did not impact central regulation of metabolism, Pavlovian conditioning, instrumental conditioning, locomotor activity, and novel-object recognition. Additionally, Sxc is integral to the regulation of neural networks. In the nucleus accumbens, we found that a loss of Sxc altered synaptic strength in a circuit specific manner. Further, we found that Sxc-mediated glutamate release is regulated by presynaptic (the neuropeptide PACAP), postsynaptic (endocannabinoid) and hormonal (glucocorticoids) signaling mechanisms. Further interrogation of Sxc regulation by PACAP revealed that this neuropeptide acts on both neurons and astrocytes to facilitate bidirectional neuron-astrocyte signaling between Sxc and extrasynaptic NMDA receptors. The in vivo relevance of this mechanism is established by our findings that PACAP microinjected into the nucleus accumbens attenuates cocaine-primed reinstatement, and the regulation of this behavior requires both Sxc and NMDA receptors. These findings support the possibility that future therapeutics could restore cognition by targeting astrocytes