The neostriatum beyond the motor function: experimental and clinical evidence.

Early suggestions about the function of the neostriatum (NS) postulated that this structure was more related to cognitive activities than to motor functions (for a review see Refs 56, 67). Since, in the past, the cerebral ventricles were thought to be the seat of ‘‘psychic spirits’’ such as imagination and memory, also the NS, which is close to the ventricles, was implicated in these cognitive functions. The first accurate anatomical description of the NS was published in 1664. Willis suggested that all incoming sensations were received by the NS. In the nineteenth century, the development of experimental research based on empirical observations of animal behaviour after various striatal manipulations supported the modulatory role of the NS in motor functions. In fact, attention was primarily focussed on the most identifiable motor symptoms while scant attention was paid to more subtle and complex changes in behaviour (for a historical review see Ref. 29). At the beginning of this century, the clinicopathological findings of Wilson strongly confirmed these concepts. He utilized the term ‘‘extrapyramidal motor system’’, previously used by Probst, to describe a structure composed of descending non-pyramidal afferents, their source and how they were variously implicated in the control of movements. The NS was considered a main constituent in this system. From the beginning of this century, this concept has been strongly reinforced by findings on the involvement of the NS in classical movement disorders like Parkinson’s disease (PD) and Huntington’s disease (HD). Only in the middle of the present century, new studies converged to revitalize interest in the cognitive functions of the NS. An important contribution in this regard was Rosvold and Delgado’s study demonstrating that manipulations of the NS caused an impairment in tasks requiring a memory component for their execution. A similar behavioural alteration was also obtained by the ablation of the prefrontal cortex, further suggesting the strong functional link between cortex and NS. From this study interest in the cognitive and behavioural functions of the NS slowly developed and today it is an important and widely accepted topic of research for neuroscientists, neurologists and psychiatrists (for recent reviews see Refs 85, 164, 177). In fact, an interesting aspect of the more recent evolution of both neurobiological studies and clinical neuropsychiatry is related to a better understanding of the physiological role of the basal ganglia and other subcortical structures in mental processes. The demonstration of long-term changes in corticostriatal synaptic transmission after repeated stimulation has provided a possible cellular substrate for the physiological processes underlying memory and learning in the NS. Advances in neuroimaging, neurophysiopathology and molecular neurobiology have revealed consistent changes in the NS in major psychiatric illnesses. Studies on the psychiatric manifestations of neurologic diseases have produced an interesting convergence of data regarding the role of the NS in behavioural symptoms. Finally, increased knowledge of electrophysiological and pharmaco‡To whom correspondence should be addressed. Abbreviations: Ach, acetylcholine; AchE, acetylcholinesterase; AMPA, alpha-amino-3-hydroxy-5-methyl-isoxazole4-propionate; CT, computed tomography; DA, dopamine; EPSP, excitatory postsynaptic potential; GPe, external globus pallidus; GPi, internal glubus pallidus; HD, Huntington’s disease; 5-HT, serotonin; HVA, high voltage-activated; IP3, inositol-1,4,5-trisphosphate; LTD, long-term depression; LTP, long-term potentiation; mGluR, metabotropic glutamate receptor; MR, magnetic resonance; NL, neuroleptic; NMDA, N-methyl-aspartate; NS, neostriatum; OCD, obsessive-compulsive disorder; 6-OHDA, 6-hydroxydopamine; PD, Parkinson’s disease; PET, positron emission tomography; SNc, substantia nigra pars compacta; SNr, substantia nigra pars reticulata; t-ACPD, trans-1-aminocyclopentane-1,3dicarboxylate. Pergamon Neuroscience Vol. 78, No. 1, pp. 39–60, 1997 Copyright ? 1997 IBRO. Published by Elsevier Science Ltd Printed in Great Britain. All rights reserved 0306–4522/97 $17.00+0.00 PII: S0306-4522(96)00556-8