tripartite synapse

Evidence for the role of astrocytes in the integration and processing of synaptic integration presents itself in a number of ways:

• Astrocytes are excitable cells: In response to stimuli from any of the three components of the tripartite synapse, astrocytes are capable of producing transient changes in their intracellular calcium concentrations through release of calcium stores from the endoplasmic reticulum{{cite journal|last1=Perea|first1=Gertrudis|title=Glial calcium signaling and neuron–glia communication|journal=Cell Calcium|date=September 2005|volume=38|issue=3–4|pages=375–382|doi=10.1016/j.ceca.2005.06.015|hdl=10261/154079|hdl-access=free}}
• Astrocytes communicate bidirectionally with neurons: Through changes in their calcium concentration excitability, astrocytes are able to detect neurotransmitters and other signals released from neurons at the synapse and can release their own neurotransmitters or gliotransmitters{{cite book|last1=Volterra|first1=A|title=The Tripartite Synapse: Glia in Synaptic Transmission|publisher=Oxford University Press|location=Chapter 13: Release of transmitters from glial cells.|pages=164–184}} that are, in turn, capable of modifying the electrophysiological excitability of neurons.{{cite journal|last1=Newman|first1=E.A.|title=New roles for astrocytes: regulation of synaptic transmission|journal=Trends in Neurosciences|date=2003|volume=26|issue=10 |pages=536–542|doi=10.1016/s0166-2236(03)00237-6|pmid=14522146}}
• Astrocytes are capable of responding selectively to stimuli: Astrocytes of the hippocampal stratum oriens form tripartite synapses with axonal projections from the alveus. The alveus projections can form either glutamatergic or cholinergic synapses with the stratum oriens, but the astrocytes of this region respond with changes in calcium concentration only to cholinergic activation of alveus projections.{{cite journal|last1=Araque|first1=Alfonso|title=Synaptically released acetylcholine evokes Ca2+ elevations in astrocytes in hippocampal slices|journal=The Journal of Neuroscience|date=1 April 2002|volume=22|issue=7|pages=2443–2450|doi=10.1523/JNEUROSCI.22-07-02443.2002 |pmid=11923408|pmc=6758296 }} This is not merely due to a sensitivity of these astrocytes exclusive to acetylcholine, as they will also respond to glutamatergic synaptic activity originating from a different brain region, the Schaffer collateral.
• Astrocytes integrate and modulate information from their synaptic inputs: Astrocytic calcium concentration changes in response to simultaneous stimulation by two neurotransmitter types is not always a linear summation (a linear summation being an increase in intracellular calcium concentration in the astrocyte in response to two simultaneous stimuli that would be the equivalent of adding the calcium concentration changes that would occur in response to each stimulation individually) of the effects of each individual input but varies by the transmitter combinations as well as frequency of stimulation. The hippocampal stratum oriens astrocytes, which respond to synaptic activity from glutamatergic neurons originating in the Schaffer collateral and cholinergic neurons originating in the alveus, produce changes in their intracellular calcium concentrations that is non-linear with the strength of synaptic input.{{cite journal|last1=Perea|first1=Gertrudis|title=Properties of Synaptically Evoked Astrocyte Calcium Signal Reveal Synaptic Information Processing by Astrocytes|journal=The Journal of Neuroscience|date=16 March 2005|volume=25|issue=9|pages=2192–2203| pmc=6726085|doi=10.1523/jneurosci.3965-04.2005|pmid=15745945|doi-access=free}} Additionally, these same stimuli are capable of producing either a potentiated calcium concentration response at low frequencies of stimulation or a depressed calcium concentration response at high frequencies of stimulation.

In a 2013 published research study titled Glutamate-Dependent Neuroglial Calcium Signaling Differ Between Young and Adult Brain, it was found that the tripartite synapse is not found in the adult brain. Earlier published research had discussed how astrocytes had metabotropic glutamate receptor 5 (mGluR5)–dependent increases in cytosolic calcium ions (Ca2+). However, astrocytic expression of mGluR5 was lost by the third postnatal week in mice and was not present in human cortical astrocytes. The results of the study indicate that neuroglial signaling the adult brain may be fundamentally different than the young brain.Glutamate-Dependent Neuroglial Calcium Signaling Differs Between Young and Adult Brain | Science

Maiken Nedergaard, M.D., D.M.Sc., lead author of the study and co-director of the University of Rochester Medical Center (URMC) Center for Translational Neuromedicine stated:

If this concept was correct, it should have given rise to a clinical trial by now. It has not, which tells us that with so many labs work on this for 20 years that there must be something wrong.

Our findings demonstrate that the tripartite synaptic model is incorrect. This concept does not represent the process for transmitting signals between neurons in the brain beyond the developmental stage.

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[https://www.youtube.com/watch?v=N3QxHf-4fUU&t=54s Study shows that current model for brain signaling is flawed (youtube.com)]

Category:Neural synapse

Category:Neuroanatomy

Category:Neurochemistry

Category:Neurology