First, a breakdown of the sensory

filter could lead to an increased stimulation of primary sensory cortical areas. Such a defective filter would implicate abnormalities in the thalamic relay nuclei. Second, dysfunction of the MD nucleus could lead to impairments of cortical association areas, especially the DLPFC. Direct evidence for an involvement of the thalamus in the pathophysiology of schizophrenia is still limited. The most convincing evidence comes from morphometric studies, pointing to a volume reduction of the thalamus, especially the MD nucleus,50,133 which Inhibitors,research,lifescience,medical has been attributed to cell loss.133 A postmortem study reported a decrease in parvalbumin-positive neurons in the anteroventral nucleus, which would result in a loss of thalamocortical projections to the prefrontal cortex.134 Recently, some135,136 but not all,137,138 neuroimaging studies have revealed smaller thalamic volume. In addition, thalamic metabolism and blood flow were found to be impaired at rest and Inhibitors,research,lifescience,medical during the performance of cognitive tasks.136,138,139 Of interest, the decrease in metabolism during the performance of a serial verbal learning test involved primarily the region of the mediodorsal thalamic nucleus.138 Basal ganglia The basal ganglia include the ventral striatum, the dorsal ZD1839 clinical trial striatum (caudate and putamcn),

and the globus pallidus. The dorsal striatum (caudate, Inhibitors,research,lifescience,medical putamen) receives input from motor cortex and projects to the globus pallidus. The globus pallidus relays the neostriatal input to the thalamus. The thalamus, in turn, projects back to the cortical areas that gave rise to the corticostriatal projections, thereby closing the cortico-striato-pallido-thalamo-cortical loop. This loop is involved in the generation and control Inhibitors,research,lifescience,medical of motor behavior. In contrast, Inhibitors,research,lifescience,medical the ventral striatum (the nucleus accumbens) is connected with the amygdala, hippocampus, and hypothalamus, and is therefore considered part of limbic system. Reward and expectancy behavior, and their

derailment during drug addiction, involve the recruitment of the nucleus accumbens. All basal ganglia structures are modulated by neurotransmitter-specific projection systems, in particular by dopaminergic neurons. Dopaminergic neurons of the SN project to the neostriatum (nigrostriatal fibers) and dopaminergic neurons of the VTA project to the nucleus accumbens (mesolimbic fibers) and cortex (mesocortical fibers). The two major DA receptors in the dorsal striatum are the D1 and D2 receptors. The nucleus accumbens expresses PAK6 primarily the D3 receptor. The basal ganglia have been a focus of interest in psychosis research for three reasons: as potential sites of neuroleptic drug action at D2 receptors, as a potential site for the generation of abnormal motor behavior during psychosis (eg, catatonia), and as a site for pathology in the limbic system.140-143 Dopaminergic afférents The most extensive search has been at the level of dopamine receptors.