Striatal neurones

The cell types of the striatum are well known (Kawaguchi, 1997), although not easy to identify in a brain slice. There are principal neurones (projection neurones), and interneurones as well. The projection neurones are all GABAergic, i.e., they use GABA as a neurotransmitter, and are the most abundant cell type. There are two kind of projection neurones; those that express Enkephalin (an endogenous opioid), and those that express substance-P, together with GABA. Morphologically, both classes are medium-size spiny neurones. It seems that they cannot be distinguished according to the morphology of the soma or dendrites.

In the striatum, one finds both GABAergic and cholinergic interneurones. One class of GABAergic interneurones expresses the calcium-binding protein Parvalbumin. These cells are very similar to the hippocampal basket cells, and can fire action potentials at a very high frequency (~50 Hz). Sometimes, they have a small soma with a pear shape (pyriform). The other class of GABAergic interneurones express somatostatin, nitric oxide (NO), and neuropeptide Y. The cholinergic interneurones are easier to identify, but difficult to find. They have very large somata, sometimes 30 µm long, and often fusiform. They show a large sag in response to a hyperpolarising current, which is due to a hyperpolarising-activated cation current (I_h). This current is often found in cells that oscillate (the I_h current is also found in heart cells). Cholinergic interneurones comprise about 2% of striatal neurones.

Striatal neuron filled with biocytin. (Picture by the author)

Degeneration of dopaminergic neurones

Parkinson's disease consists in the degeneration of dopaminergic neurones from the substantia nigra pars compacta. Knowing why dopaminergic neurones degenerate would be an important step toward the cure. Two recent articles provide some clues (Avshalumov et al., 2005; Liss et al., 2005).
The article by Liss et al., point out that in Parkinson's disease other dopaminergic neurones, such as those from the ventral tegmental area (VTA) are spared, and they examined the differences between the two populations accordingly. They noticed that the VTA neurones have a smaller ATP-dependent K current (Kir-6.2), and the calcium-binding protein calbinding was more frequently found there. The mouth-watering result is that removal of the Kir-6.2 turns the dopaminergic cells insensitive to MPTP (a substance that induces cell death that resembles Parkinson's disease). The obvious conclusion is that K-ATP is required for cell death. Then, they tried to find differences in the K-ATP channel in the two cell types (VTA and substantia nigra), but found nothing substantial. So, they concluded that "cell-specific differences in the channel regulation are expected." But we do not know what these differences are.
The second article by Ashalumlov et al., makes complementary observations. The authors recorded from dopaminergic neurones using a dye that is sensitive to hydrogen peroxide (H₂O₂). The H₂O₂ has gained a reputation for producing oxidative damage in cells. But here it activates the K-ATP channel. Using their technique, they could see the increase in H₂O₂ as the living neuron fires a train of action potentials. If they let the H₂O₂ accumulate by blocking the peroxidase enzyme, some cells hyperpolarise due to the activation of a K-ATP channel. And they found that only the cells expressing the regulatory SUR1 subunit did so.
What we learn from these two articles is that oxidative stress lead to the production of H₂O₂, which activates the K-ATP dependent channel producing cell death. One could speculate that the cells that die are those unable to hyperpolarise (i.e., those expressing SUR2), and the dopaminergic cell will keep producing H₂O₂ to dangerous level without being able to activate the K-ATP. Of course, this idea should wait for experimental verification. Stay tuned.

What is the striatum?

The striatum forms part of the basal ganglia, the portion of the brain involved in the control of voluntary movement, and participates in emotional, motivational, associative, and cognitive aspects of movement as well (Herrero et al., 2002). The basal ganglia belong to the extrapyramidal system as there is no direct connection to the spinal cord. The basal ganglia also control facial muscles and voluntary saccadic eye movements (Hikosaka, et al., 2000). The basal ganglia are important also because they are affected by Parkinson’s disease, which is now recognised to occur worldwide (Zhang and Roman, 1993, Zhang et al., 2005).
Anatomically, the basal ganglia comprise a set of synaptically connected structures, whose main input from the cortex is the corpus striatum, which corresponds to the nuclei caudatus and putamen in humans. The striatum, located inside the capsula interna, anterior to the thalamus, projects to the medial and lateral portions of the globus palidus, located medially with respect to the striatum. The nucleus subthalamicus, located ventrally with respect to the thalamus underneath the area tegmentalis, receives inputs from the lateral portion of the globus palidus, and projects to the substantia nigra pars reticulata, forming the indirect pathway. The projection from the striatum to the medial portion of the globus palidus constitutes the direct pathway. An important portion of the basal ganglia is the substantia nigra pars compacta that projects to the striatum.
The main input to the basal ganglia is the cerebral cortex, which projects to the striatum. The main output is to the thalamus. It is now accepted that the maps in the basal ganglia are topographycally organised. The striatum, for example, contains two partially overlapping body maps arising from the primary motor cortex and supplementary motor cortex respectively (Romanelli et al., 2005). This separation is not only anatomical, but also functional. Among the two outputs of the basal ganglia to the thalamus, the GPi conveys sensory-motor information, and the SNr conveys associative and cognitive information.