Now I study oligodendrocyte development, and if you ask me they are a truly unappreciated cell type. Here is yet one more piece of evidence: synapses have been detected between neurons and oligodendrocytes in CA1 of the hippocampus AND these synapses can undergo a kind of LTP.

Glial cells in the central nervous system (CNS) constitute a heterogeneous population of cell types. Macroglia-like NG2 cells express the chondriotin sulfate proteoglycan NG2 and have been described as oligodendrocyte precursor cells (OPCs) or given other names. NG2 cells in the CA1 area of the hippocampus receive direct glutamatergic and {gamma}-aminobutyric acid (GABA)-ergic synaptic inputs from neurons. The structure of the neuron-glia synapses found in NG2 cells differs from that of neuronal synapses by having a less well-defined postsynaptic density and smaller presynaptic boutons that contain fewer vesicles. With the exception of developing neuromuscular junctions, long-term potentiation (LTP) has been observed only at synapses between neurons. Thus it is of interest to examine whether the neuron-NG2 cell synapses have adequate expression and localization of components required for both the induction and expression of LTP.

Whole-cell recordings were made from NG2 cells in the CA1 region of rat hippocampal slices. Glial cell membrane currents induced by the stimulation of Schaffer collaterals (SCs) were used to monitor rapid neuron-glial signaling. The identity of astrocytes and NG2 cells was determined by both electrophysiological recording and immunostaining. Staining with antibodies to glial fibrillary acidic protein (GFAP) and NG2 revealed two distinct nonoverlapping cell populations. NG2 cells were identified by having a relatively high input resistance (131.7 ± 5.4 megohms, n = 160 cells), large transient A-type currents (IA) and delayed rectifier K+ currents (IK), and small tetrodotoxin (TTX)-sensitive Na+ currents that failed to generate typical action potentials. We found no detectable voltage-dependent Ca2+ currents in these cells. When cells with the above characteristics were marked by intracellular loading with biocytin or lucifer yellow and subsequently immunostained with an antibody against NG2, all of the cells (14 out of 14) were found to be NG2-positive. (Citations removed.)

They go on to characterize these cells electrophysiologically and pharmacologically. Here is a trace from one of the cells after tetanic stimulation:

See how the response rises. That is glial long term potentiation (gLTP).

This paper has a bunch of details, so I don't have time to go into everything but there are a couple of interesting things about these glial synapses.

Below shows the Ca influx into an oligodendrocyte (NG-2 positive) cell treated by glutamate, as measured by the Ca-sensitive dye Rhod2:

If you look at the traces, this Ca influx is suppressed entirely by DNQX (a non-NMDA channel blocker), showing that the source of the Ca is different that the typical source in neurons. They go on to show that the source of the calcium is Ca-permeable AMPA receptors.

They also show that the gLTP requires this Ca influx, just like neurons.

Crazy town. They don't really show any purpose for this, but I am sure there is something. Here is their speculation:

The conversion of CaPARs [Ca-permeable AMPA receptors] into Ca2+-impermeable receptors at Bergmann glial cells, by transfection with the GluR2 subunit, results in the retraction of glial processes that ensheath synapses and multiple innervations of Purkinje cells by climbing fibers. Pathological insults such as ischemia also down-regulate GluR2 expression in OPCs and neurons, leading to the expression of CaPARs and enhanced glutamate toxicity after ischemia. Thus, an adequate level of activity by CaPARs is important for maintaining normal synaptic structure and function. Glutamate receptor activation is linked to the proliferation and differentiation of OPCs, and NG2 cells can differentiate into neurons both in vitro and in vivo. The expression of gLTP and the elevation of CaPARs in SC-NG2 synapses may thus contribute to activity-dependent neuronal regulation of NG2 cell differentiation. Like astrocytes, NG2 cells may also secrete neuroactive factors to regulate neuronal functions. Rapid neuron-NG2 cell signaling may allow rapid feedback regulation of neuronal functions by Ca2+-dependent secretion of neuroactive factors, and the strength of such feedback regulation will increase after the induction of gLTP. (Emphasis mine. Citations removed.)

I have only one philosophical principle: The world is always more complicated than you think.

Thanks world for proving me right yet again.

Hat-tip: Faculty of 1000.