Tag Archives: dopamine D1 receptor

Do glia think?

Do glia think Dr. Gonatas?  This was part of an exchange between G. Milton Shy, head of neurology at Penn, and Nick Gonatas a brilliant neuropathologist who worked with Shy as the two of them described new disease after new disease in the 60s ( myotubular (centronuclear) myopathy, nemaline myopathy, mitochondrial myopathy and oculopharyngeal muscular dystrophy).

Gonatas was claiming that a small glial tumor caused a marked behavioral disturbance, and Shy was demurring.  Just after I graduated, the Texas Tower shooting brought the question back up in force — https://en.wikipedia.org/wiki/University_of_Texas_tower_shooting.

A recent paper [ Neuron vol. 105 pp. 954 – 956, 1036 – 1047 ’20] gives good evidence that glia are more than the janitors and the maintenance crew of the brain.

Glia cover most synapses (so neurotransmitter there doesn’t leak out, I thought) giving rise to the term tripartite synapse (presynaptic terminal + postsynaptic membrane + glial covering).

Here’s what they studied.  The cerebral cortex projects some of its axons (which use glutamic acid as a neurotransmitter) to a much studied nucleus in animals (the nucleus accumbens).  This is synapse #1. The same nucleus gets a projection of axons from the brainstem ventral tegmental area (VTA) which uses dopamine as a neurotransmitter.  However, the astrocytes (a type of glia) covering synapse #1 have the D1 dopamine receptor (there are 5 different dopamine receptors) on them.  It isn’t clear if the dopamine neurons actually synapse (synapse #2) on the astrocytes, or whether the dopamine  just leaks out of the synaptic cleft to the covering glia.

Optogenetic stimulation of the VTA dopamine neurons results in an elevation of calcium in the astrocytes (a sign of stimulation). Chemogenetic activation of these astrocytes depresses the presynaptic  terminals of the neurons projecting the nucleus accumbens  from the cerebral cortex .  How does this work?  Stimulated astrocytes release ATP or its produce adenosine.  This binds to the A1 purinergic receptor on the presynaptic terminal of the cortical projection.

So what?

The following sure sounds like the astrocyte here is critical to brain function.  Activation of the astrocyte D1 receptor contributes to the locomotor hyperactivity seen after an injection of amphetamine.

Dopamine is intimately involved in reward, psychosis, learning and other processes (antipsychotics and drugs for hyperactivity manipulate it).  That the humble astrocyte is involved in dopamine action takes it out of the maintenance crew and puts it in to management.

A final note about Dr. Shy.  He was a brilliant and compelling teacher, and instead of the usual 1% of a medical school class going into neurology, some 5% of ours did.  In 1967 he ascended to the chair of the pinnacle of American Neurology at the time, Columbia University.  Sadly, he died the month he assumed the chair.  Scuttlebut has it that he misdiagnosed his own heart attack as ‘indigestion’ and was found dead in his chair.