Category Archives: glia cells

Another change in the picture

As I have pointed out in previous postings, there are important new discoveries about the brain every month or so. This time we have a whole new signaling pathway in the brain. This involves new knowledge of biochemistry, physiology and anatomy. This is not a minor addition to knowledge of the brain.

ScienceDaily reports (here) on the paper: (Sakry, Neitz, Singh, Frischknecht, Marongiu, Binamé, Perera, Endres, Lutz, Radyushkin, Trotter, Mittmann; Oligodendrocyte Precursor Cells Modulate the Neuronal Network by Activity-Dependent Ectodomain Cleavage of Glial NG2; PLoS Biology, 2014; 12 (11)).

There are a number of glia cell types. Oligodendrocytes are the glia that myelinate axons by wrapping around them, insulating and speeding transmission along the axons. They develop from a precursor cell – but this precursor is a wide spread, stable and significant (5-8%) cell type in the brain. The OPC (oligodendrocyte progenitor cells) were shown, a few years ago, to form synapses with neurons and to receive signals from neurons through these synapses, but this was thought to be a one-way communication.

“We have now discovered that the precursor cells do not only receive information via the synapses, but in their turn use these to transmit signals to adjacent nerve cells. They are thus an essential component of the network,” explained Professor Jacqueline Trotter… Classically, neurons have been considered as the major players in the brain. Over the past few years, however, increasing evidence has come to light that glial cells may play an equally important role. “Glial cells are enormously important for our brains and we have now elucidated in detail a novel important role for glia in signal transmission,” explained Professor Thomas Mittmann…

A signal from the neuron results in reactions in the OPC that releases a fragment of a protein (NG2) into the local environment where it affects neighbouring neurons’ synapses altering their electrical activity. “The role of NG2 in this process became apparent when the researchers removed the protein: neuronal synaptic function is altered, modifying learning and disrupting the processing of sensory input that manifests in the form of behavioral changes in test animals.

The way brain networks function is much more complex than our models and less understood than we assumed. I believe there will be many more surprises.

Astrocyte role in gamma waves

The study of the brain has been very neuron centered. Glial cells outnumber neuron by about 10 to 1 in the cortex and are known to be important to brain function but it is not clear just what they do other than some housekeeping tasks and shepherding neurons to their final locations during development. Astrocyte roles appear to be important but unknown.

Now Lee et al, (see citation below) have published an excellent paper showing one role connected with gamma oscillations. The work was very impressive, but too specialized to describe here – it is summarized in the abstract below. The paper really ‘nailed down’ one role of the astrocytes.

In hippocampus slices they showed that astrocyte intercellular calcium rises before the start of gamma oscillations . This rise does not trigger the gamma but is required for the waves to have duration. They were able to block glutamate release of astrocytes without affecting neuron activity and showed that this glutamate release was the mechanism for maintaining gamma duration. They developed a strain of mouse where astrocyte glutamate release could be switched on and off, and again they showed that neuron behavior was not affected. When the glutamate release from astrocytes was blocked, the gamma power spectrum decreased in the 20 to 40 Hz range. The power spectrum decrease happened only during waking and not in REM or non-REM sleep. The behavior of the mice was examined. There was no difference in maze navigation or in fear conditioning, but novel object recognition was defective when the mice were turned ‘off’ and normal when they were ‘on’. So gamma oscillation in the hippocampus is required for novel object recognition and this ability depends on glutamate release from astrocytes.

They explain in their discussion why there would be a difference in the three behavior tests. “Although both the Y-maze task and the NOR test rely on the rodent’s innate exploratory behavior in the absence of externally applied positive or negative reinforcement, defects were selectively observed in the case of the NOR test. This is particularly relevant because the Y-maze task evaluates a simpler form of memory processing, i.e., short-term spatial working memory, whereas NOR involves a higher memory load engaging long-term storage, retrieval, and restorage of memory processing. During the test phase of the NOR test, a novel object needs to be detected and encoded, whereas the memory trace of a familiar object needs to be updated and reconsolidated after long delays. In contrast, fear conditioning might constitute a strong and highly specific form of learning involving a sympathetic reflex reaction with suppression of voluntary movements (freezing), in which subtle changes in memory content might not be detectable. Moreover, there is strong evidence that suggests fear-conditioned learning encodes a long-term memory process involving the amygdala and the hippocampus, whereas the NOR paradigm engages different structures: the hippocampus and adjacent cortical areas including entorhinal, perirhinal, and parahippocampal cortex.”

Here is the abstract:

Glial cells are an integral part of functional communication in the brain. Here we show that astrocytes contribute to the fast dynamics of neural circuits that underlie normal cognitive behaviors. In particular, we found that the selective expression of tetanus neurotoxin (TeNT) in astrocytes significantly reduced the duration of carbachol-induced gamma oscillations in hippocampal slices. These data prompted us to develop a novel transgenic mouse model, specifically with inducible tetanus toxin expression in astrocytes. In this in vivo model, we found evidence of a marked decrease in electroencephalographic (EEG) power in the gamma frequency range in awake-behaving mice, whereas neuronal synaptic activity remained intact. The reduction in cortical gamma oscillations was accompanied by impaired behavioral performance in the novel object recognition test, whereas other forms of memory, including working memory and fear conditioning, remained unchanged. These results support a key role for gamma oscillations in recognition memory. Both EEG alterations and behavioral deficits in novel object recognition were reversed by suppression of tetanus toxin expression. These data reveal an unexpected role for astrocytes as essential contributors to information processing and cognitive behavior.

Perhaps astrocytes are involved in the production of other brain waves in other locations too.
ResearchBlogging.org

Lee, H., Ghetti, A., Pinto-Duarte, A., Wang, X., Dziewczapolski, G., Galimi, F., Huitron-Resendiz, S., Pina-Crespo, J., Roberts, A., Verma, I., Sejnowski, T., & Heinemann, S. (2014). Astrocytes contribute to gamma oscillations and recognition memory Proceedings of the National Academy of Sciences, 111 (32) DOI: 10.1073/pnas.1410893111

I'm on ScienceSeeker-Microscope