Sleep-like behavior is a fundamental property of the tripartite synapse

Abstract

The tripartite synapse, consisting of the presynaptic neuron, post-synaptic neuron, and an astrocyte, is considered to be the main locus of signaling between neurons in the brain.1,2 Neurotransmission is energetically very expensive3,4, and the primary neurotransmitter utilized for signaling is glutamate. It has been found that glutamate is also used as a substrate for energy generation.5,6 However, it is unclear what the relationship is between energy generation and availability of neurotransmitter during glutamatergic neurotransmission. Here we show that availability of energy, represented by adenosine triphosphate (ATP), and glutamate for neurotransmission are intimately related, and in fact determine the ability to signal at the tripartite synapse. Using a novel neurochemical mathematical model of the tripartite synapse, we found that glutamate concentrations for neurotransmission and ATP concentrations were interdependent, and their interplay controlled the firing pattern of the presynaptic terminal, as defined by synaptic vesicle release. Furthermore, we found that depending on the parameters chosen in the model, the tripartite synapse demonstrated behavior with limit cycles, alternating between high- and low-frequency firing rates. Our results show that complex behavior with high- and low-activity states, qualitatively meeting the characteristics of sleep7 emerges directly from the nature of the tripartite synapse, with glutamate and ATP concentrations serving as the signals for state changes. We anticipate that our model will serve as a starting point to further elucidate the energetics of neuronal and brain functioning, and eventually shed light on the fundamental question of the nature and necessity of sleep.

Prospects and Potentiality of Lentil in Nepal: Food Security and Trade Perspective

“…The emphasis on pulses and farmer subsidies by the Indian government have enhanced production. Bangladesh has also made lentils a prioritized crop, increasing both cultivation area and yield (Joshi, 2020). Over the last 10 years, global demand for lentil has grown at a healthy annual rate of 6.2 percent, and it is projected that export earnings from lentil in Nepal may double or treble if appropriate measures are adopted to increase production area, productivity, and market integration (USAID, 2013;ITC, 2007).…”