Search bioRxiv⌕ Search
Home/Archive/bioRxiv

bioRxiv · 10.1101/2022.11.10.516040

Dopamine facilitates the response to glutamatergic inputs in a computational model of astrocytes

Bezerra, T. O.·Roque, A. C.
View original source ↗Export metadata ↓

Abstract

Astrocytes are active cells that respond to neurotransmitters with elevations in their intracellular calcium concentration (calcium signals). In a tripartite synapse involving two neurons coupled by a glutamatergic synapse and one astrocyte, glutamate released by the presynaptic neuron can generate calcium signals in the astrocyte, which in turn trigger the release of neuroactive molecules (gliotransmitters) by the astrocyte that bind to receptors in the pre- and postsynaptic neuron membranes and modulate synaptic transmission. Astrocytic calcium signals can also be evoked by dopamine released in distant sites. Little is known about how dopamine modulates glutamatergic-evoked astrocyte activity. To investigate this question, we constructed compartmental astrocyte models with three different morphologies: linear (soma plus a single branch); branched (soma plus two branches); and bifurcated (soma plus a single branch that bifurcates into two branchlets). Compartments were modeled by conductance-based equations for membrane voltage and transport of ions, glutamate and dopamine between extra- and intracellular spaces. Glutamatergic and dopaminergic stimuli were modeled as Poisson processes with variable frequencies, and astrocyte responses were measured by number and location of evoked calcium signals. For cells with linear morphology, whole-cell dopaminergic stimulation reduced the glutamatergic stimulation frequency of distal compartments needed to generate calcium signals. For both the branched and bifurcated morphologies, whole-cell dopaminergic stimulation together with glutamatergic stimulation of one of the processes reduced the glutamatergic stimulation frequency necessary to trigger a calcium signal in the other process. The same glutamatergic stimulation protocols without dopamine stimulation required higher glutamatergic input frequencies to evoke calcium signals. Our results suggest that dopamine facilitates the occurrence of glutamatergic-evoked calcium signals, and that dopamine-glutamate interaction can control the distribution of calcium signals along the astrocyte extension. Author summaryAstrocytes are brain cells that are not electrically excitable as neurons but display chemical excitability in the form of transient rises in the intracellular calcium concentration (calcium signals) evoked by neurotransmitters. A tripartite synapse consists of pre- and postsynaptic terminals ensheathed by astrocyte processes. Neurotransmitters released by the presynaptic neuron can generate calcium signals in the astrocyte, which in turn trigger the release of neuroactive molecules (gliotransmitters) by the astrocyte that bind to receptors in the pre- and postsynaptic membranes and modulate synaptic transmission. Two neurotransmitters that can evoke astrocytic calcium signals are glutamate, the major neurotransmitter of excitatory synapses, and dopamine, an important modulatory neurotransmitter that can diffuse to wider regions than the synaptic release site. Little is known about how dopamine modulates glutamatergic-evoked astrocyte activity, and here we investigate this question using computational modeling. We constructed compartmental astrocyte models with three different morphologies: linear, with a single branch emanating from soma; branched, with two branches emanating from soma; and bifurcated, with a branch emanating from soma that bifurcates into two branchlets. Compartments were modeled by conductance-based equations for membrane voltage and transport of ions (sodium, potassium and calcium), glutamate and dopamine between extra- and intracellular spaces. Glutamatergic and dopaminergic stimuli were modeled as Poisson processes with variable frequencies. Astrocyte models with the three morphologies were submitted to similar stimulation protocols to compare their responses, which were measured in terms of the frequency and location of evoked calcium signals. For cells with linear morphology, dopaminergic stimulation of the entire cell (to simulate the diffuse action of dopamine) reduced the glutamatergic stimulation frequency of distal compartments (which simulates glutamatergic input from presynaptic neuron) needed to generate calcium signals. For both the branched and bifurcated morphologies, dopaminergic stimulation of the whole cell together with glutamatergic stimulation of the distal portions of one of the processes reduced the glutamate stimulation frequency necessary to trigger a calcium signal in the distal portions of the other process. Repetitions of the glutamatergic stimulation protocols without whole cell dopaminergic stimulation showed that higher glutamatergic input frequencies were needed to evoke calcium signals. Our results suggest that dopamine facilitates the occurrence of calcium signals evoked by glutamatergic inputs, and that interaction between dopamine and glutamate can control the distribution of calcium signals along the astrocyte extension.

Explore related subjects

neurosciencePreprint

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Bezerra, T. O., Roque, A. C.. 2022-11-11. Dopamine facilitates the response to glutamatergic inputs in a computational model of astrocytes. https://doi.org/10.1101/2022.11.10.516040

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

Connexin 40 deficiency alters the temporal profile of postictal oxygen dynamics following focal seizures.

Epilepsy is increasingly recognized as a disorder involving both neuronal and vascular dysfunction. While connexin signaling has been implicated in epileptogenesis, the contribution of vascular connexins to seizure associated cerebrovascular pathology remains poorly understood. Connexin40 (Cx40) is an endothelial gap junction protein that plays a crucial role in vascular communication and blood-flow regulation. Seizures induce dynamic changes in cerebral perfusion and oxygenation, including prolonged postictal hypoperfusion/hypoxia. To determine whether Cx40 influences postictal hypoxia following focal seizures, we examined seizure characteristics and postictal oxygen dynamics in Cx40 knockout (Cx40-/-) mice using an established focal hippocampal seizure model. Electrically kindled seizures were elicited in wild-type and Cx40-/- mice, and local hippocampal tissue oxygenation was continuously monitored before and after seizure induction. Seizure duration did not differ between genotypes, indicating comparable seizure severity. Interestingly, Cx40 deletion altered the temporal pattern of postictal oxygen recovery, producing greater early hypoxia and a delayed secondary rebound in pO2 despite similar peak oxygen levels and overall hypoxic burden. These findings demonstrate that loss of Cx40 selectively alters the temporal profile of postictal oxygen dynamics without affecting seizure duration. Taken together, the results suggest that endothelial gap junctional communication contributes to postictal vascular recovery and identify Cx40 as a potential modulator of seizure associated neurovascular dysfunction.

neuroscience↗
bioRxiv2026

Attention Across Scales: From Individual Variation to Social Hierarchies and Brain Networks in Semi-Free-Ranging Macaques

Attention is a fundamental brain function supporting perception, decision-making, and social behavior, and its dysfunction profoundly impairs daily life. It is both dynamic and stable, varying across observations and individuals, changing across the lifespan, and being shaped by social and environmental experience. Yet capturing this complexity remains a central challenge in neuroscience. Here, we integrated longitudinal behavioral assessments of semi-free-ranging macaques living in naturalistic social groups with resting-state fMRI. We quantified performance across days, ages, and social hierarchies and related it to intrinsic brain organization. Distinct attentional phenotypes emerged, including individuals with reduced attentional control. Performance followed an inverted-U lifespan trajectory, improving from childhood to adulthood before declining. Social status modulated attentional performance. Critically, nonlinear lifespan trajectories and associations with individual attentional differences were most clearly expressed in frontoparietal connectivity. Together, these findings reveal how sustained attention is organized across scales, providing a biological framework for its individual diversity, social modulation, and neural basis.

neuroscience↗
bioRxiv2026

Decoding natural scenes from patterned optogenetic responses in mouse visual cortex

A central challenge in developing visual cortical prostheses is to determine how visual stimuli should be transformed into effective patterns of cortical stimulation. Although advances in stimulation technologies, including optogenetics, provide increasingly precise control over cortical activity, it remains unclear whether artificially evoked activity can reproduce the information content of naturally evoked visual representations. Here we establish a quantitative framework for evaluating visual encoding strategies by decoding cortical responses evoked by natural vision and patterned optogenetic stimulation. We developed a novel dual-modal paradigm in awake mice to bridge the gap between endogenous photostimulation and artificial network driving. By co-expressing the high-performance calcium indicator GCaMP6s and the red-shifted, ultra-sensitive opsin rsChRmine-oScarlet in the primary visual cortex (V1), we successfully translated dynamic natural movie frames into patterned, spatiotemporal optogenetic stimulation. Quantitative comparisons of macro-scale dynamics demonstrated that this patterned optogenetic injection evokes cortical states highly comparable and representationally aligned with those driven by actual visual photostimulation. To systematically evaluate the fidelity of these responses, we developed STAR, a deep learning model featuring spatial and temporal attention mechanisms, and successfully reconstructed the frames of natural movies from V1 signals under both experimental modalities. Collectively, our results demonstrate that complex sensory information can be both naturally encoded and synthetically injected into V1 circuits with high decoding fidelity. This work provides an empirical and computational proof-of-concept for intelligent, closed-loop biomimetic encoders, establishing a robust framework for next-generation cortical visual neuroprostheses and bidirectional brain-machine interfaces.

neuroscience↗