ATP

Hippocampal granule cell (GC) models exhibit degeneracy with different ion channel parameters resulting in comparable functional behaviour [1,2]. However, it is unknown how the degenerate models are further constrained by energetic considerations and known computational functions of GCs. Here, we use Pareto optimality to investigate this question. The Pareto perspective is particularly useful for multi-objective optimisation with multiple trade-offs [3]. We assume that evolution constrains and simplifies the ion channel parameter space by favouring Pareto optimal neurons, which cannot improve

ATP/Adenosine, a type of neurotransmitter, has recently attracted attention as damage-associated molecular patterns (DAMPs) and has been reported to play an important role in the induction of inflammation via inflammasome. On the other hand, there have been few reports on in vivo measurements of ATP and adenosine in the synaptic cleft and/or extracellular spaces.Generally, in vivo measurement of neurotransmitter content in the synaptic cleft and/or extracellular spaces has been performed mainly by invasive methods such as micro dialysis. However, recently, GPCR-activation-based (GRAB) sensor w

…astrocytic AQP4 induces the release of ATP and subsequent increase of extracellular adenosine. Since antagonistic interactions between adenosine and dopamine have been shown by biochemical and pharmacological studies, the present study investigated the possibility that the AQP4-dependent adenosine increase interacts with dopamine neurotransmission, focusing on the effects of cocaine. The stimulus effect of acute cocaine treatment was abolished in AQP4 ko mice, while mice treated with caffeine for one week showed the increase of the stim

…During ALS, ATP released by neurons and glial cells modulates the neuroglial interplay via activation of P2X receptors. Among these, P2X4 receptor, which is a non-selective cationic channel, has been recently involved in ALS pathogenesis. We found that both the absence of P2X4 or the increase of surface P2X4 using P2X4KO or non-internalized P2X4KI mice respectively, have a beneficial outcome in the SOD1 mice. This paradoxical output suggests a complex cell-role of P2X4 in

…various cellular metabolites, such as ATP or cAMP. Due to the spectral characteristics of these tools, different assemblies of optical hardware are usually needed to reveal the full potential of various biosensors. In a

Neural cells and tissue injury lead to abundant release of ATP from the cell. Additionally, ATP could be cut loose through the activated Pannexin 1 hemichannels. Extracellular ATP could activate P2X7R, P2 ligand-gated ion channels, activating the inflammasome in microglia and astrocytes. P2X7R and Panx1 could create forward feedback loop, that potentiates and drives the chronicity of previously initiated neuroinflammation. Both P2X7R and Panx1 are upregulated in multiple neurodegenerative diseases, hypoxia, injuries, depression, epilepsy, and pain. Targeting one or both P2X7R and Panx1 has bec

Obesity and metabolic diseases are a top priority challenge for health systems. Monitoring changes in the body’s energy levels is a task of the hypothalamus which integrates the actions of peripheral hormones and nutrients with neural information. Among the cells involved, tanycytes play a key role. They are glial cells that line the third ventricle and mediate information about changes in the circulation to various hypothalamic nuclei. They regulate important neuroendocrine functions such as food intake and energy balance. Although tanycytes are known to integrate external and internal signal

Purinergic P2X receptors (P2XR) are activated by ATP, with 7 different subunits capable of forming homo- or heterotrimeric channels. Widely expressed in the nervous system, P2XR have been implicated in neurological diseases, such as Alzheimer's disease, where overexpression of P2X2, P2X4 and P2X7 is observed. Despite decades of research into their function and structure, few P2XR structures and specific negative modulators have been described. Human P2X2 (hP2X2) and P2X4 (hP2X4) structures are not available, posing challenges for designing more effective and specific modulators.In this study,

Neurons rely on mitochondria for an efficient supply of ATP and other metabolites. However, while neurons are highly elongated, mitochondria are discrete and limited in number. Due to the slow rates of diffusion over long distances it follows that neurons would benefit from an ability to control the distribution of mitochondria to sites of high metabolic activity, such as synapses. It is assumed that neurons’ possess this capacity, but ultrastructural data over substantial portions of a neuron’s extent that would allow for tests of such hypotheses are scarce. Here, we mined the Caenorhabditis

…resulting in the production of ATP and lactate. Brain lactate is mainly produced by astrocytes through a process called aerobic glycolysis, while neurons, being high oxidative cells, preferentially use mitochondrial respiration to produce ATP. In this frame, astrocytes provide lactate to neurons, in a process called astrocytes to neurons lactate shuttle. Lactate is not only important as a metabolic support i

…, driving loss of NAD and changes in ATP , ROS and calcium. Animal models caused by genetic mutation, toxins, viruses or metabolic defects can be alleviated by blocking programmed axon death, for example models of CMT1B , chemotherapy-induced peripheral neuropathy (CIPN

…propose that it is the accumulation of ATP in neuronal mitochondria, and that

Coordinated activity across networks of neurons is a hallmark of both resting and active behavioral states in many species, including worms, flies, fish, mice and humans. These global patterns alter energy metabolism in the brain over seconds to hours, making oxygen consumption and glucose uptake widely used proxies of neural activity. However, whether changes in neural activity are causally related to changes in metabolic flux in intact circuits on the sub-second timescales associated with behavior, is unclear. Moreover, it is unclear whether differences between rest and action are associated

Spontaneous firing, observed in many neurons, is often attributed to ion channel or network level noise. Cortical cells during slow wave sleep exhibit transitions between so called Up and Down states. In this sleep state, with limited sensory stimuli, neurons fire in the Up state. Spontaneous firing is also observed in slices of cholinergic interneurons, cerebellar Purkinje cells and even brainstem inspiratory neurons. In such in vitro preparations, where the functional relevance is long lost, neurons continue to display a rich repertoire of firing properties. It is perplexing that these neuro