Mglu-r1-hebbain-learning

A train of thoughts runs on a well orchestrated subway

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Networks in the brain resemble the london underground, filled with interconnected circuits. In case of the brain, trains are replaced by electrical signals, tracks by neurons, and stations by synapses. Is it not remarkable that the term “train of thoughts” was introduced as early as in 1651 by Thomas Hobbes in his Leviathan, long before we knew anything about neurons or synapses, or electric signals? Much like stations with more incoming trains are made bigger, synapses with frequently incoming trains of electric signals are made stronger. This plasticity of synapses – termed Long term potentiation (LTP) – is achieved by time-synchronized activity between a specific presynaptic and a specific postsynaptic neuron – a process called spike timing-dependent plasticity. The synced activity nudges both neurons into making all kinds of molecular and receptor changes, and finally ending up with strong synapses. And the currency of this interaction is Calcium ions. A recent paper has delved into the role of calcium ions in this process and come up with some new insights.use of The authors used  patch clamp recordings and two photon microscopy has delved into the role of calcium ions in this process and come up with some new insights into  the complex symphony of receptors in the dendritic spine – an outgrowth on the neuron that literally forms the synapse – of neurons in the hippocampus.

LTP is not about the sheer number of calcium ions rushing in, but rather about a  well coordinated traffic system that allows calcium to get green lights at the right channels at the right times.

Earlier studies have shown that LTP is characterized by increased inflow of calcium ions in the postsynaptic neuron, which tip this neuron towards excitation. But this study finds LTP induction to be independent of the amount of calcium ions or amplitude of calcium currents coming in via NMDARs – glutamate receptors that allows positive ions like sodium and calcium to flow through the membrane. However, Tigaret et al. show that LTP requires sequential activation of NMDAR followed by another calcium gate called VSCC (voltage-sensitive calcium channel). Furthermore, LTP needs a roadblock being set up for SK channels, which tend to otherwise jam up the NMDAR expressway for calcium. The authors further identify the stationmaster that regulates these SK channels – a protein that goes by the name mGLUR1  (because perisynaptic group 1 metabotropic receptors just scares people away!).

Thus, LTP induction appears to be associated with patterned activation of specific calcium channels on the synapses, with NMDARs and VSCCs aiding in inflow of calcium transients while mGLUR1 maintaining activation of NMDARs by blocking SK receptors.  So it seems, LTP is not about the sheer number of calcium ions rushing in, but rather about a  well coordinated traffic system that allows calcium to get green lights at the right channels at the right times. While the quest to elucidate the molecular mechanisms involved in LTP will go on, let us be glad for the remarkable subway in our heads and get the our train of thoughts running wild.

 

Original article: http://www.nature.com/ncomms/2016/160113/ncomms10289/full/ncomms10289.html

Artwork: Utkarsha Singh