The objectives of this project are to determine (1) the regional distribution of cholinergic, GABAergic and glutamatergic parameters within the striatum (caudate nucleus), and (2) the relationship among these neuronal systems in this region of the brain, especially with respect to the striatal cholinergic interneurons. Distribution studies will be performed using striatal samples obtained from frontal serial sections of the brain. The rostrocaudal distribution of cholinergic interneurons will be assessed from determinations of choline acetyltransferase activity, choline uptake, acetylcholinesterase activity and muscarinic receptor binding. The regional distribution of GABAergic neurons will be evaluated from data obtained on GABA uptake, glutamic acid decarboxylase activity, endogenous levels of GABA and GABA receptor binding. To study the distribution of glutamatergic terminals within the striatum, and more specifically, those glutamatergic terminals with cells of origin in the frontal cortex, glutamate uptake will be determined in control and cortical ablated animals. High affinity glutamate uptake will serve as an index of glutamatergic innervation and the technique of cortical ablation will be employed as a means of interrupting cortical afferents to the striatum. Choline uptake has the capacity to change with alterations in neuronal activity. Thus, choline uptake will be determined in synaptosomes following intrastriatal injection of appropriate agonists and antagonists, in order to determine the effect of GABAergic and glutamatergic neuronal inputs on the activity of striatal cholinergic neurons. If striatal GABAergic neurons exert an inhibitory effect on cholinergic interneurons in the striatum, then intrastriatal injection of GABA agonists and antagonists should result in decreased and increased choline uptake, respectively. Similarly, if glutamatergic neurons of cortical origin exert a tonic excitatory influence on striatal cholinergic interneurons, removal of this input (cortical ablation) should result in a decrease in choline uptake, and it may be possible to reverse this effect by intrastriatal injection of glutamate or kainic acid, a glutamate agonist.