Topic: ATP

Programmed axon death is a widespread and completely preventable mechanism in injury and disease. Mouse and Drosophila studies define a molecular pathway involving activation of SARM1 NA Dase and its prevention by NAD synthesising enzyme NMNAT2 . Loss of axonal NMNAT2 causes its substrate, NMN , to accumulate and activate SARM1 , 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

Neurons spike spontaneously in many experimental settings. Such firing patterns are often characterized by prolonged periods of silence followed by an unknown trigger of spontaneous activity that propagates throughout the slice. These were dubbed `neural avalanches' as they resemble avalanches in which accumulated snow rapidly flows down a mountain slope. Expanding this analogy -- if the network connectivity is equivalent to the mountain slope, what is the 'snow' that accumulates prior to a neural avalanche? Here, we 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

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