101 research outputs found
Multiple forms of working memory emerge from synapse-astrocyte interactions in a neuron-glia network model
Persistent activity in populations of neurons, time-varying activity across a neural population, or activity-silent mechanisms carried out by hidden internal states of the neural population have been proposed as different mechanisms of working memory (WM). Whether these mechanisms could be mutually exclusive or occur in the same neuronal circuit remains, however, elusive, and so do their biophysical underpinnings. While WM is traditionally regarded to depend purely on neuronal mechanisms, cortical networks also include astrocytes that can modulate neural activity. We propose and investigate a network model that includes both neurons and glia and show that glia-synapse interactions can lead to multiple stable states of synaptic transmission. Depending on parameters, these interactions can lead in turn to distinct patterns of network activity that can serve as substrates for WM
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
Coexistence of amplitude and frequency modulations in intracellular calcium dynamics
The complex dynamics of intracellular calcium regulates cellular responses to
information encoded in extracellular signals. Here, we study the encoding of
these external signals in the context of the Li-Rinzel model. We show that by
control of biophysical parameters the information can be encoded in amplitude
modulation, frequency modulation or mixed (AM and FM) modulation. We briefly
discuss the possible implications of this new role of information encoding for
astrocytes.Comment: 4 pages, 4 figure
Systematic sequencing of mRNA from the Antarctic krill (Euphausia superba) and first tissue specific transcriptional signature
BACKGROUND: Little is known about the genome sequences of Euphausiacea (krill) although these crustaceans are abundant components of the pelagic ecosystems in all oceans and used for aquaculture and pharmaceutical industry. This study reports the results of an expressed sequence tag (EST) sequencing project from different tissues of Euphausia superba (the Antarctic krill).
RESULTS: We have constructed and sequenced five cDNA libraries from different Antarctic krill tissues: head, abdomen, thoracopods and photophores. We have identified 1.770 high-quality ESTs which were assembled into 216 overlapping clusters and 801 singletons resulting in a total of 1.017 non-redundant sequences. Quantitative RT-PCR analysis was performed to quantify and validate the expression levels of ten genes presenting different EST countings in krill tissues. In addition, bioinformatic screening of the non-redundant E. superba sequences identified 69 microsatellite containing ESTs. Clusters, consensuses and related similarity and gene ontology searches were organized in a dedicated E. superba database http://krill.cribi.unipd.it.
CONCLUSION: We defined the first tissue transcriptional signatures of E. superba based on functional categorization among the examined tissues. The analyses of annotated transcripts showed a higher similarity with genes from insects with respect to Malacostraca possibly as an effect of the limited number of Malacostraca sequences in the public databases. Our catalogue provides for the first time a genomic tool to investigate the biology of the Antarctic krill
A roadmap to integrate astrocytes into Systems Neuroscience
Systems Neuroscience is still mainly a neuronal field, despite the plethora of evidence supporting the fact that astrocytes modulate local neural circuits, networks, and complex behaviors. In this article, we sought to identify which types of studies are necessary to establish whether astrocytes, beyond their well-documented homeostatic and metabolic functions, perform computations implementing mathematical algorithms that sub-serve coding and higher-brain functions. First, we reviewed Systems-like studies that include astrocytes in order to identify computational operations that these cells may perform, using Ca transients as their encoding language. The analysis suggests that astrocytes may carry out canonical computations in time scales of sub-seconds to seconds in sensory processing, neuromodulation, brain state, memory formation, fear, and complex homeostatic reflexes. Next, we propose a list of actions to gain insight into the outstanding question of which variables are encoded by such computations. The application of statistical analyses based on machine learning, such as dimensionality reduction and decoding in the context of complex behaviors, combined with connectomics of astrocyte-neuronal circuits, are, in our view, fundamental undertakings. We also discuss technical and analytical approaches to study neuronal and astrocytic populations simultaneously, and the inclusion of astrocytes in advanced modeling of neural circuits, as well as in theories currently under exploration, such as predictive coding and energy-efficient coding. Clarifying the relationship between astrocytic Ca and brain coding may represent a leap forward towards novel approaches in the study of astrocytes in health and disease.Junior Leader Fellowhip Program by 'la Caixa' Banking Foundation, LCF/BQ/LI18/11630006
BFU2017-85936-P
BFU2016-75107-P
BFU2016-79735-P
FLAGERA-PCIN-2015-162-C02-02
HHMI 55008742
FPU13/05377
NIH R01NS099254
NSF 1604544
Agència de Gestio d’Ajuts Universitaris i de Recerca, 2017 SGR54
Sequence learning in Associative Neuronal-Astrocytic Network
The neuronal paradigm of studying the brain has left us with limitations in
both our understanding of how neurons process information to achieve biological
intelligence and how such knowledge may be translated into artificial
intelligence and its most brain-derived branch, neuromorphic computing.
Overturning our fundamental assumptions of how the brain works, the recent
exploration of astrocytes is revealing that these long-neglected brain cells
dynamically regulate learning by interacting with neuronal activity at the
synaptic level. Following recent experimental evidence, we designed an
associative, Hopfield-type, neuronal-astrocytic network and analyzed the
dynamics of the interaction between neurons and astrocytes. We show that
astrocytes were sufficient to trigger transitions between learned memories in
the neuronal component of the network. Further, we mathematically derived the
timing of the transitions that was governed by the dynamics of the
calcium-dependent slow-currents in the astrocytic processes. Overall, we
provide a brain-morphic mechanism for sequence learning that is inspired by,
and aligns with, recent experimental findings. To evaluate our model, we
emulated astrocytic atrophy and showed that memory recall becomes significantly
impaired after a critical point of affected astrocytes was reached. This
brain-inspired and brain-validated approach supports our ongoing efforts to
incorporate non-neuronal computing elements in neuromorphic information
processing.Comment: 8 pages, 5 figure
High IGFBP2 expression correlates with tumor severity in pediatric rhabdomyosarcoma
Rhabdomyosarcoma (RMS) is the most common childhood sarcoma and is identified as either the embryonal or alveolar (ARMS) subtype. In approximately 75% of cases, ARMSs are characterized by specific chromosomal translocations that involve PAX and FKHR genes. ARMS gene expression signatures vary, depending on the presence or absence of the translocations. Insulin-like growth factor-binding protein 2 (IGFBP2) is strongly overexpressed in translocation-negative RMS. Because IGFBP2 is associated with tumorigenesis, we investigated its functional role in RMS. An analysis of IGFBP2 distribution in RMS cell lines revealed a strong accumulation in the Golgi complex, in which morphological characteristics appeared peculiarly modified. After silencing IGFBP2 expression, our microarray analysis revealed mostly cell cycle and actin cytoskeleton gene modulations. In parallel, IGFBP2-silenced cells showed reduced cell cycle and rates of invasion and decreased seeding in the lungs after tail vein injections in immunodeficient mice. An analysis of IGFBP2 mRNA and protein localization in human tumors showed abnormal protein accumulation in the Golgi complex, mostly in PAX/FKHR-negative RMS. Moreover, an analysis of patients with RMS revealed the presence of conspicuous circulating levels of IGFBP2 proteins in children with highly aggressive RMS tumors. Taken together, our data provide evidence that IGFBP2 contributes to tumor progression and that it could be used as a marker to better classify clinical and biological risks in RMS
Nonlinear gap junctions enable long-distance propagation of pulsating calcium waves in astrocyte networks
A new paradigm has recently emerged in brain science whereby communications
between glial cells and neuron-glia interactions should be considered together
with neurons and their networks to understand higher brain functions. In
particular, astrocytes, the main type of glial cells in the cortex, have been
shown to communicate with neurons and with each other. They are thought to form
a gap-junction-coupled syncytium supporting cell-cell communication via
propagating Ca2+ waves. An identified mode of propagation is based on
cytoplasm-to-cytoplasm transport of inositol trisphosphate (IP3) through gap
junctions that locally trigger Ca2+ pulses via IP3-dependent Ca2+-induced Ca2+
release. It is, however, currently unknown whether this intracellular route is
able to support the propagation of long-distance regenerative Ca2+ waves or is
restricted to short-distance signaling. Furthermore, the influence of the
intracellular signaling dynamics on intercellular propagation remains to be
understood. In this work, we propose a model of the gap-junctional route for
intercellular Ca2+ wave propagation in astrocytes showing that: (1)
long-distance regenerative signaling requires nonlinear coupling in the gap
junctions, and (2) even with nonlinear gap junctions, long-distance
regenerative signaling is favored when the internal Ca2+ dynamics implements
frequency modulation-encoding oscillations with pulsating dynamics, while
amplitude modulation-encoding dynamics tends to restrict the propagation range.
As a result, spatially heterogeneous molecular properties and/or weak couplings
are shown to give rise to rich spatiotemporal dynamics that support complex
propagation behaviors. These results shed new light on the mechanisms
implicated in the propagation of Ca2+ waves across astrocytes and precise the
conditions under which glial cells may participate in information processing in
the brain.Comment: Article: 30 pages, 7 figures. Supplementary Material: 11 pages, 6
figure
A tale of two stories: astrocyte regulation of synaptic depression and facilitation
Short-term presynaptic plasticity designates variations of the amplitude of
synaptic information transfer whereby the amount of neurotransmitter released
upon presynaptic stimulation changes over seconds as a function of the neuronal
firing activity. While a consensus has emerged that changes of the synapse
strength are crucial to neuronal computations, their modes of expression in
vivo remain unclear. Recent experimental studies have reported that glial
cells, particularly astrocytes in the hippocampus, are able to modulate
short-term plasticity but the underlying mechanism is poorly understood. Here,
we investigate the characteristics of short-term plasticity modulation by
astrocytes using a biophysically realistic computational model. Mean-field
analysis of the model unravels that astrocytes may mediate counterintuitive
effects. Depending on the expressed presynaptic signaling pathways, astrocytes
may globally inhibit or potentiate the synapse: the amount of released
neurotransmitter in the presence of the astrocyte is transiently smaller or
larger than in its absence. But this global effect usually coexists with the
opposite local effect on paired pulses: with release-decreasing astrocytes most
paired pulses become facilitated, while paired-pulse depression becomes
prominent under release-increasing astrocytes. Moreover, we show that the
frequency of astrocytic intracellular Ca2+ oscillations controls the effects of
the astrocyte on short-term synaptic plasticity. Our model explains several
experimental observations yet unsolved, and uncovers astrocytic
gliotransmission as a possible transient switch between short-term paired-pulse
depression and facilitation. This possibility has deep implications on the
processing of neuronal spikes and resulting information transfer at synapses.Comment: 93 pages, manuscript+supplementary text, 10 main figures, 11
supplementary figures, 1 tabl
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