Striatum and the neurophysiology of movement

Neuroscience research related to the striatum and basal ganglia.

Thursday, April 10, 2008

Cadherins

The striatum is a complex structure. The origin of this complexity is its homogeneity. Structurally, the striatum can be compared to a noodle soup, mostly เส้นหมี่ full of medium-spiny neurones with a round soma resembling ลูกชิ้น and occasionally here and there, a เกี้ยวทอด, a giant cholinergic neurone.

The striatum lacks of obvious inner structure. There are no cytoarchitectonics differences that might help to design some sort of Broadmann areas. There is no evident anatomical unit like the Purkinje cell-climbing fibre of the cerebellum, of the CA1-CA3 pyramidal cells of the hippocampus. Nevertheless, the striatum ought to have some organisation. After all, the frontal cortex projects to the rostral striatum, sensorimotor cortex to the dorsolateral portion, and the parietal cortex to the caudal tail. This anatomical division is an expression of the non-motor functions of the striatum.

The patchy nature of the striatum is the closest approximation to a global structure. Here, the striatum is considered as a Swiss cheese, in which the matrix will be the cheesy part, and the striosoma will be represented by the holes. The matrix of the striatum can be revealed by somatostatin, acetycholinesterase, enkephalin, of calbinding stainings. The islands that form the striosoma can be visualised with opiate receptors, substance P, or tyrosine hydroxylase stainings. The current thinking (Gerfen, 1992) holds that the medium-spiny neurones of the matrix projects to the globus palidus lateralis forming the indirect pathway. The medium-spiny projection neurones of the striosoma, on the other hand, project to the globus palidus medialis, forming the direct pathway.

Another approach to define molecular territories in the striatum is to examine the molecular texture of the neurons. Extracellular-matrix molecules (here matrix means the outside of the cells no relation to the striatal matrix) that act as a glue sticking cells together. Examples of such molecules are cadherins, or calcium-dependent cell adhesion molecules. Hertel et al. (2008) studied the striatal expression of 12 cadherins; four true cadherins (Cdh4, Cdh7, Cdh8, and Cdh11), and eight protocadherins (Pcdh1, Pcdh7, Pcdh8, Pcdh9, Pcdh10, Pcdh11, Pcdh17, and Pcdh19). Except for Cd11 and Pcdh1 (that are exclusive to the striosome), all other cadherins are expressed in the matrix. Some cadherins had weak expression (Pcdh8), other were expressed everywhere (Cdh11), while some have high expression rostrally decreasing caudally (Pcdh7, Pcdh17, Pcdh11), while other have exactly the opposite pattern (Pcdh19). Thus, cadherins may define territories in the basal ganglia in the same way that ephrins do in the lateral geniculate nucleus guiding the axons coming from the appropriate regions of the retina. In the striatum there are also ephrins that play a role in delineating the matrix-striosome compartments.

Tuesday, April 01, 2008

Dendrites caught releasing dopamine

Synaptic transmission is the process by which a nerve cell releases a neurotransmitter substance to cause the excitation of a nearby neuron. Sir Bernard Katz described the details of this process in the neuromuscular synapse long time ago. When it seems that there is nothing new about a process recounted in thousand of textbooks, surprising results come from examining dopaminergic cells in the substantia nigra pars compacta (SNc).

The SNc is not part the striatum; it is located in the midbrain, more caudally. It provides the dopaminergic inputs that modulate the corticostriatal synapse by mechanism that are not completely clear. Results from the group of Laurent Venance in France (Vandercasteele et al., 2008) show surprising finding in the way that dopaminergic cells contact each other. They examined synaptic transmission between dopaminergic cells. This may sound strange, but it happen that dopaminergic cells not only modulate the corticostriatal synapse, but in doing so, they talk to each other. Recording from two cells shows that action potentials in one cell produce a hyperpolarising response in the other cell. The obvious explanation would be that they release GABA. However, when bicuculline was added, the response did not change. The authors added many other things to the pairs. Once they added the D2-receptor blocker raclopride, then the depolarisation vanished. So the transmission is clearly dopaminergic.

The mechanism of action seems to be inhibition of the hyperpolarisation-activated current Ih (also called HCN, the same current that makes the pacemaker in heart cells). The transmission between SNc neurones disappears after adding ZD7288, the classical Ih blocker. In addition, they show that membrane conductance decreases during transmission, and depolarisation of the post-synaptic cell (that would close the HCN channels) also decreases and eventually eliminates the transmission. These new findings support curious early observations (Chéramy et al., 1981, Chéramy et al., 1983) that SNc dendrites can release dopamine.