A local glutamate-glutamine cycle sustains synaptic excitatory transmitter release. 2014

Hiroaki Tani, and Chris G Dulla, and Zoya Farzampour, and Amaro Taylor-Weiner, and John R Huguenard, and Richard J Reimer
Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA. Electronic address: hirotaniwork@gmail.com.

Biochemical studies suggest that excitatory neurons are metabolically coupled with astrocytes to generate glutamate for release. However, the extent to which glutamatergic neurotransmission depends on this process remains controversial because direct electrophysiological evidence is lacking. The distance between cell bodies and axon terminals predicts that glutamine-glutamate cycle is synaptically localized. Hence, we investigated isolated nerve terminals in brain slices by transecting hippocampal Schaffer collaterals and cortical layer I axons. Stimulating with alternating periods of high frequency (20 Hz) and rest (0.2 Hz), we identified an activity-dependent reduction in synaptic efficacy that correlated with reduced glutamate release. This was enhanced by inhibition of astrocytic glutamine synthetase and reversed or prevented by exogenous glutamine. Importantly, this activity dependence was also revealed with an in-vivo-derived natural stimulus both at network and cellular levels. These data provide direct electrophysiological evidence that an astrocyte-dependent glutamate-glutamine cycle is required to maintain active neurotransmission at excitatory terminals.

UI MeSH Term Description Entries
D009435 Synaptic Transmission The communication from a NEURON to a target (neuron, muscle, or secretory cell) across a SYNAPSE. In chemical synaptic transmission, the presynaptic neuron releases a NEUROTRANSMITTER that diffuses across the synaptic cleft and binds to specific synaptic receptors, activating them. The activated receptors modulate specific ion channels and/or second-messenger systems in the postsynaptic cell. In electrical synaptic transmission, electrical signals are communicated as an ionic current flow across ELECTRICAL SYNAPSES. Neural Transmission,Neurotransmission,Transmission, Neural,Transmission, Synaptic
D009474 Neurons The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM. Nerve Cells,Cell, Nerve,Cells, Nerve,Nerve Cell,Neuron
D004558 Electric Stimulation Use of electric potential or currents to elicit biological responses. Stimulation, Electric,Electrical Stimulation,Electric Stimulations,Electrical Stimulations,Stimulation, Electrical,Stimulations, Electric,Stimulations, Electrical
D005971 Glutamates Derivatives of GLUTAMIC ACID. Included under this heading are a broad variety of acid forms, salts, esters, and amides that contain the 2-aminopentanedioic acid structure. Glutamic Acid Derivatives,Glutamic Acids,Glutaminic Acids
D005973 Glutamine A non-essential amino acid present abundantly throughout the body and is involved in many metabolic processes. It is synthesized from GLUTAMIC ACID and AMMONIA. It is the principal carrier of NITROGEN in the body and is an important energy source for many cells. D-Glutamine,L-Glutamine,D Glutamine,L Glutamine
D006624 Hippocampus A curved elevation of GRAY MATTER extending the entire length of the floor of the TEMPORAL HORN of the LATERAL VENTRICLE (see also TEMPORAL LOBE). The hippocampus proper, subiculum, and DENTATE GYRUS constitute the hippocampal formation. Sometimes authors include the ENTORHINAL CORTEX in the hippocampal formation. Ammon Horn,Cornu Ammonis,Hippocampal Formation,Subiculum,Ammon's Horn,Hippocampus Proper,Ammons Horn,Formation, Hippocampal,Formations, Hippocampal,Hippocampal Formations,Hippocampus Propers,Horn, Ammon,Horn, Ammon's,Proper, Hippocampus,Propers, Hippocampus,Subiculums
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001253 Astrocytes A class of large neuroglial (macroglial) cells in the central nervous system - the largest and most numerous neuroglial cells in the brain and spinal cord. Astrocytes (from "star" cells) are irregularly shaped with many long processes, including those with "end feet" which form the glial (limiting) membrane and directly and indirectly contribute to the BLOOD-BRAIN BARRIER. They regulate the extracellular ionic and chemical environment, and "reactive astrocytes" (along with MICROGLIA) respond to injury. Astroglia,Astroglia Cells,Astroglial Cells,Astrocyte,Astroglia Cell,Astroglial Cell,Astroglias,Cell, Astroglia,Cell, Astroglial
D013569 Synapses Specialized junctions at which a neuron communicates with a target cell. At classical synapses, a neuron's presynaptic terminal releases a chemical transmitter stored in synaptic vesicles which diffuses across a narrow synaptic cleft and activates receptors on the postsynaptic membrane of the target cell. The target may be a dendrite, cell body, or axon of another neuron, or a specialized region of a muscle or secretory cell. Neurons may also communicate via direct electrical coupling with ELECTRICAL SYNAPSES. Several other non-synaptic chemical or electric signal transmitting processes occur via extracellular mediated interactions. Synapse
D017207 Rats, Sprague-Dawley A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company. Holtzman Rat,Rats, Holtzman,Sprague-Dawley Rat,Rats, Sprague Dawley,Holtzman Rats,Rat, Holtzman,Rat, Sprague-Dawley,Sprague Dawley Rat,Sprague Dawley Rats,Sprague-Dawley Rats

Related Publications

Hiroaki Tani, and Chris G Dulla, and Zoya Farzampour, and Amaro Taylor-Weiner, and John R Huguenard, and Richard J Reimer
August 2007, The Journal of neuroscience : the official journal of the Society for Neuroscience,
Hiroaki Tani, and Chris G Dulla, and Zoya Farzampour, and Amaro Taylor-Weiner, and John R Huguenard, and Richard J Reimer
August 2006, The Journal of neuroscience : the official journal of the Society for Neuroscience,
Hiroaki Tani, and Chris G Dulla, and Zoya Farzampour, and Amaro Taylor-Weiner, and John R Huguenard, and Richard J Reimer
March 1995, Neuroendocrinology,
Hiroaki Tani, and Chris G Dulla, and Zoya Farzampour, and Amaro Taylor-Weiner, and John R Huguenard, and Richard J Reimer
November 2018, Journal of neuroendocrinology,
Hiroaki Tani, and Chris G Dulla, and Zoya Farzampour, and Amaro Taylor-Weiner, and John R Huguenard, and Richard J Reimer
December 1994, The Journal of physiology,
Hiroaki Tani, and Chris G Dulla, and Zoya Farzampour, and Amaro Taylor-Weiner, and John R Huguenard, and Richard J Reimer
May 1994, Proceedings of the National Academy of Sciences of the United States of America,
Hiroaki Tani, and Chris G Dulla, and Zoya Farzampour, and Amaro Taylor-Weiner, and John R Huguenard, and Richard J Reimer
November 1990, Science (New York, N.Y.),
Hiroaki Tani, and Chris G Dulla, and Zoya Farzampour, and Amaro Taylor-Weiner, and John R Huguenard, and Richard J Reimer
November 1996, Journal of neurophysiology,
Hiroaki Tani, and Chris G Dulla, and Zoya Farzampour, and Amaro Taylor-Weiner, and John R Huguenard, and Richard J Reimer
January 1993, Developmental neuroscience,
Hiroaki Tani, and Chris G Dulla, and Zoya Farzampour, and Amaro Taylor-Weiner, and John R Huguenard, and Richard J Reimer
January 1987, Annual review of neuroscience,
Copied contents to your clipboard!