Abstract
The excitatory synaptic transmission is mediated by glutamate (GLU) in neuronal networks of the mammalian brain. In addition to the synaptic GLU, extra-synaptic GLU is known to modulate the neuronal activity. In neuronal networks, GLU uptake is an important role of neurons and glial cells for lowering the concentration of extracellular GLU and to avoid the excitotoxicity. Monitoring the spatial distribution of intracellular GLU is important to study the uptake of GLU, but the approach has been hampered by the absence of appropriate GLU analogs that report the localization of GLU. Deuterium-labeled glutamate (GLU-D) is a promising tracer for monitoring the intracellular concentration of glutamate, but physiological properties of GLU-D have not been studied. Here we study the effects of extracellular GLU-D for the neuronal activity by using primary cultured rat hippocampal neurons that form neuronal networks on microelectrode array. The frequency of firing in the spontaneous activity of neurons increased with the increasing concentration of extracellular GLU-D. The frequency of synchronized burst activity in neurons increased similarly as we observed in the spontaneous activity. These changes of the neuronal activity with extracellular GLU-D were suppressed by antagonists of glutamate receptors. These results suggest that GLU-D can be used as an analog of GLU with equivalent effects for facilitating the neuronal activity. We anticipate GLU-D developing as a promising analog of GLU for studying the dynamics of glutamate during neuronal activity.
Highlights
The neuronal network in dissociated culture of neurons has been used as a model system for studying the neuronal network in the brain [1,2,3,4], as the system shows the mechanisms that are essential for learning, memory, and cognition [5,6,7,8]
In order to examine the spontaneous activity of neurons in neuronal networks, a microelectrode array (MEA) has been used, which is composed of a grid-shape arrangement of multiple planar microelectrodes fabricated on a substrate
By using MEA, previous studies have shown that the spontaneous firing rates of cultured neurons reflected the neuronal activity that was altered by the concentration change of extracellular glucose [23]
Summary
The neuronal network in dissociated culture of neurons has been used as a model system for studying the neuronal network in the brain [1,2,3,4], as the system shows the mechanisms that are essential for learning, memory, and cognition [5,6,7,8]. Spontaneous firing of action potentials in neurons can be observed in cultured networks [9,10,11,12,13], and that has been reported to be one of the bases for the brain functions [14,15,16]. By using MEA, previous studies have shown that the spontaneous firing rates of cultured neurons reflected the neuronal activity that was altered by the concentration change of extracellular glucose [23]. Array-wide synchrony of spontaneous neuronal activity can be analyzed with MEA by simultaneously monitoring the extracellular potentials of synaptically connected multiple neurons [17,18,19]. MEA is a useful tool to monitor the activity of neuronal networks that is altered by the conditions of extracellular environment
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