Nuclear morphology of medium spiny neurons in the striatum

The major input of the basal ganglia, the striatum, contains ~ 6 cell types, primarily: 1) medium spiny neurons ( ~ 96%), 2) Deiter’s neurons (2%), 3) cholinergic interneurons (1%; tonically active but usually stop firing in response to reward). Medium spiny neurons are particularly interesting little buggers.

All medium spiny neurons in the striatum express at least one of DR1 and DR2 receptors, and a minority express both. They receive dopamine-based (“dopaminergic”) input from the substantia nigra that modulates the neurons’ responses to glutamate-based excitatory input from the cortex, hippocampus, amygdala, and etc.

Medium spiny neurons themselves use GABA as their neurotransmitter and thus have an inhibitory effect on the neurons in the globus pallidus that their axons project to.

Dopamine input increases the intrinsic excitability of medium spiny neurons in part by decreasing the inactivation rate of their inhibitory A-type potassium channels. Azdad et al (here) show how rats with pharmacologically-depleted dopamine also have decreased spine density in their medium spiny neurons:

two-photon confocal microscopy in 280 µm thick stratial slices; doi:10.1371/journal.pone.0006908

So, this is possibly a homeostatic regulation system whereby dopamine-based changes in the morphology of medium spiny neurons is accommodated for by channel-based increases in excitability.

Identifying this type of neuron in section slices accurately is a major challenge of circuitry analysis. Matamales et al (here) have shown that one way to identify the types of cells in the striatum is by staining their nuclei with a dsDNA intercalating fluorescent molecule (TO-PRO-3). This allows nuclear diameter, nuclear shape, and heterochromatin distribution to be visualized.

As opposed to traditional antibodies specific to one type of molecule (red in the following figure), the nuclear DNA morphology-based system is useful for classifying cells using just one type of marker:

mouse striatal slices labeled and visualized w confocal microscopy ; doi:10.1371/journal.pone.0004770

The authors note that “similar nuclear appearances were observed for principal neurons in other brain regions such as pyramidal neurons of the cerebral cortex,” suggesting that their method might be broadly useful in other brain regions, too.

Finally, here is a 3d reconstruction of a medium spiny neuron from a mouse collected using multiphoton imaging:

gray = regions of dendrite too thin to trace ; cell centered database image basename ACC1

One day there will probably be a massive database with probabilistic reconstructions of many of these types of neurons arrayed in some sort of physiologically relevant order. How the world will change…

References

Martone, M. E., Gupta, A., Wong, M., Qian, X., Sosinsky, G., Ludaescher, B., and Ellisman, M. H. A cell centered database for electron tomographic data. J. Struct. Biology 138: 145-155, 2002.

Azdad K, Chàvez M, Bischop PD, Wetzelaer P, Marescau B, et al. (2009) Homeostatic Plasticity of Striatal Neurons Intrinsic Excitability following Dopamine Depletion. PLoS ONE 4(9): e6908. doi:10.1371/journal.pone.0006908

Matamales M, Bertran-Gonzalez J, Salomon L, Degos B, Deniau J-M, et al. (2009) Striatal Medium-Sized Spiny Neurons: Identification by Nuclear Staining and Study of Neuronal Subpopulations in BAC Transgenic Mice. PLoS ONE 4(3): e4770. doi:10.1371/journal.pone.0004770