38 research outputs found
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 Ca2+ transients as their encoding language. The analysis suggests that astrocytes may carry out canonical computations in a time scale of subseconds 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, is, 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 Ca2+ and brain coding may represent a leap forward toward novel approaches in the study of astrocytes in health and disease
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
On the determinants of calcium wave propagation distance in astrocyte networks: nonlinear gap junctions and oscillatory modes
A new paradigm has recently emerged in brain science whereby glial cells should be considered on a par with neurons to understand higher brain functions. In particular, astrocytes, the main type of glial cells in the cortex, are thought to form a gap-junction-coupled syncytium supporting cell-cell communication via propagating calcium (Ca2+) waves. The propagation properties of these waves and their relations to intracellular signalling dynamics are however poorly understood. Here, we propose a novel model of the gap-junctional route for intercellular Ca2+ wave propagation in astrocytes that yields two major predictions. First, we show that long-distance regenerative signalling requires gap junctions with nonlinear transport properties. Second, we show that even with nonlinear gap junctions, long-distance regenerative signalling is favoured when 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 give rise to rich spatiotemporal dynamics and support complex propagation behaviours. These results suggest that the large variability of the wave propagation range that is consistently reported by experimental studies, is a result of the association of nonlinear gap junctions with heterogeneous astrocyte populations and/or low coupling
Distinctive biophysical features of human cell-types: insights from studies of neurosurgically resected brain tissue
Electrophysiological characterization of live human tissue from epilepsy patients has been performed for many decades. Although initially these studies sought to understand the biophysical and synaptic changes associated with human epilepsy, recently, it has become the mainstay for exploring the distinctive biophysical and synaptic features of human cell-types. Both epochs of these human cellular electrophysiological explorations have faced criticism. Early studies revealed that cortical pyramidal neurons obtained from individuals with epilepsy appeared to function “normally” in comparison to neurons from non-epilepsy controls or neurons from other species and thus there was little to gain from the study of human neurons from epilepsy patients. On the other hand, contemporary studies are often questioned for the “normalcy” of the recorded neurons since they are derived from epilepsy patients. In this review, we discuss our current understanding of the distinct biophysical features of human cortical neurons and glia obtained from tissue removed from patients with epilepsy and tumors. We then explore the concept of within cell-type diversity and its loss (i.e., “neural homogenization”). We introduce neural homogenization to help reconcile the epileptogenicity of seemingly “normal” human cortical cells and circuits. We propose that there should be continued efforts to study cortical tissue from epilepsy patients in the quest to understand what makes human cell-types “human”
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
Glutamate regulation of calcium and IP3 oscillating and pulsating dynamics in astrocytes
Recent years have witnessed an increasing interest in neuron-glia
communication. This interest stems from the realization that glia participates
in cognitive functions and information processing and is involved in many brain
disorders and neurodegenerative diseases. An important process in neuron-glia
communications is astrocyte encoding of synaptic information transfer: the
modulation of intracellular calcium dynamics in astrocytes in response to
synaptic activity. Here, we derive and investigate a concise mathematical model
for glutamate-induced astrocytic intracellular Ca2+ dynamics that captures the
essential biochemical features of the regulatory pathway of inositol
1,4,5-trisphosphate (IP3). Starting from the well-known two-state Li-Rinzel
model for calcium-induced-calcium release, we incorporate the regulation of the
IP3 production and phosphorylation. Doing so we extended it to a three-state
model (referred as the G-ChI model), that could account for Ca2+ oscillations
triggered by endogenous IP3 metabolism as well as by IP3 production by external
glutamate signals. Compared to previous similar models, our three-state models
include a more realistic description of the IP3 production and degradation
pathways, lumping together their essential nonlinearities within a concise
formulation. Using bifurcation analysis and time simulations, we demonstrate
the existence of new putative dynamical features. The cross-couplings between
IP3 and Ca2+ pathways endows the system with self-consistent oscillator
properties and favor mixed frequency-amplitude encoding modes over pure
amplitude modulation ones. These and additional results of our model are in
general agreement with available experimental data and may have important
implications on the role of astrocytes in the synaptic transfer of information.Comment: 42 pages, 16 figures, 1 table. Figure filenames mirror figure order
in the paper. Ending "S" in figure filenames stands for "Supplementary
Figure". This article was selected by the Faculty of 1000 Biology: "Genevieve
Dupont: Faculty of 1000 Biology, 4 Sep 2009" at
http://www.f1000biology.com/article/id/1163674/evaluatio