etters t o t h e Model for basal ganglia disorders SIR: The recent review on 'The functional anatomy of basal ganglia disorders '1 raised several interesting if not controversial points. The first is that although the article acknowledges its bias towards the motor functions of the basal ganglia, the anatomical description is incomplete and misleading. The neostriatum receives input not only from the thalamus, raphe nucleus and neocortex but also has an input from limbic structures such as the amygdala 2'3. Furthermore, the output of the basal ganglia via the thalamus and brainstem is as much to non-motor as motor areas and these include the prefrontal cortex, posterior parietal cortex and raphe nucleus 4-6. The importance of such relationships does emphasize the non-motor, possibly cognitive, functions of the basal ganglia 7. Second, there is some doubt about the inhibitory input from the basal ganglia to the thalamus 8-1° especially if one considers the organization of the thalamus. The thalamus is said to have the same organization regardless of nucleus (and this includes the intralaminar nucleus) 4, and to receive universally prethalamic afferents that are excitatory to relay cells. The inhibitory output from the globus pallidus and substantia nigra to it is thus at variance with this observation (see also Ref. 10). However, it is possible that this inhibitory output can be transformed into an excitatory one to the relay cells by one of two (or possibly both) mechanisms. First, the inhibitory input may selectively synapse on the GABAergic local circuit neurones, which in turn make inhibitory synapses on the thalamocortical relay cells, although the evidence is that all thalamic afferents synapse onto both cell types 4. Second, the inhibitory input may hyperpolarize the relay cell into the range of membrane potential where it responds to small excitatory inputs with rapid high-frequency bursts of discharges 11.12. The importance of TINS, Vol. 13, No. 3, 1990

this is that the basal ganglia effects on the thalamus would be better accommodated by the earlier model of Young and Penney 13, rather than the one presented. A third issue involves the controversy of the effect of the dopaminergic input to the neostriatum, in terms of whether it is excitatory or inhibitory to the output neurones of this structure. Although in the model the predominant effect appears to be inhibitory, there is a body of evidence, and this includes transplantation experiments, that dopamine is excitatory to the output neurones 14. Furthermore, the assumption that the subthalamic nucleus is all-important in the pathogenesis of movement disorders of the basal ganglia, means that the striatonigral projection appears to be largely unimportant. Finally, in Fig. 2 of the article the important excitatory motor cortical input to the subthalamic nucleus is not shown. This input may be as important, if not more so, than the disinhibition from the neostriatum in producing some of the clinical effects of the diseases discussed. Despite these criti-

cisms, however, their model is of interest and does provide a possible mechanism of pathogenesis of basal ganglia movement disorders. Roger Barker 18SchubertRoad,LondonSW15, UK.

References

1 Albin, R. L., Young, A. B. and Penney, J. B. (1989) Trends Neurosci. 12, 366-375 2 Kelley, A. E., Domesick, V. B. and Nauta, W. (1982) Neuroscience 7, 615-630 3 Russchen,F. T., Bakst, I., Amaral, D. and Price,J. L. (1985) Brain Res. 329, 241-257 4 Jones, E. G. (1985) in The Thalamus Plenum Press 5 Kievit, J. and Kuypers, H. G. J. M. (1977) Exp. Brain Res. 29, 299-322 6 Barnes,C. D., Fung, S. L. and Adams, W. L. (1979) Pain 6, 207-215 7 Barker, R. A. (1988) J. Theoret. Biol. 131,499-507 8 Purpura, D. P. (1975) PharmacoL Ther. B 1, 17-26 9 Dormont, J. F. and Ohje, T. (1971) Exp. Brain Res. 12, 254-264 10 Isacson,O., Brudin, P., Kelly, P. A. T., Gage, F. H. and Bjorklund, A. (1984) Nature 311,458-460 11 Jahnsen, H. and Llinas, R. R. (1984) J. PhysioL (London) 349, 205-247 12 Pape, H-C. and McCormick, D. A. (1989) Nature 340, 715-718 13 Penney,J. B. and Young, A. B. (1983) Annu. Rev. Neurosci. 6, 73-94 14 Sirinathsinghji, D. J. S. et el. (1988) Neuroscience 24, 803-811

Role of the mesostriatal dopamine pathway

amine receptors and their mechanisms of action, the excitatory and inhibitory effects of dopSIR: amine (DA) on different popuThe mesostriatal dopamine path- lations of striatal cells have to be way links the substantia nigra explained at the cellular level. (pars compacta) to the striatum The mesostriatal cells form and is important in regulating symmetrical synapses on the striatal function as shown by the predominant output cell of the example of Parkinson's disease striatum, the medium-sized spiny where this pathway is damaged. cell 2'3. Synapses are onto cell There has been much discussion bodies, dendritic shafts and denabout the role of this pathway dritic spines. Where a spine reand whether it is excitatory or ceives a mesostriatal synapse, inhibitory to striatal cell activity. there will also be a second input In their recent article Albin et el. with an asymmetrical synapse conclude that it is excitatory on nearer the spine head from exsome striatal cells [the principal citatory glutamatergic corticooutput cells that project to the striatal fibres. Some cortical fibres medial globus pallidus and sub- synapse onto spine heads that do stantia nigra (pars reticulata) and not have a mesostriatal input. carry information to the thala- These observations would be mus] and inhibitory on other out- consistent with inhibitory effects put cells (cells projecting to the of DA at the synaptic level but the lateral globus pallidus and thence functional effects on striatal cell to the subthalamic nucleus) 1. For activity may be different dependthose of us interested in dop- ing on the subcellular localization. 93