The capacity to predict future events permits a creature to detect, model, and manipulate the causal structure of its interactions with its environment. Behavioral experiments suggest that learning is driven by changes in the expectations about future salient events such as rewards and punishments. Physiological work has recently complemented these studies by identifying dopaminergic neurons in the primate whose fluctuating output apparently signals changes or errors in the predictions of future salient and rewarding events. Taken together, these findings can be understood through quantitative theories of adaptive optimizing control.

/pdf/a-neural-substrate-of-prediction-and-reward-2tj1zqgoih.pdf

A Neural Substrate of Prediction and Reward

Schultz, Wolfram. Predictive reward signal of dopamine neurons. J. Neurophysiol. 80: 1–27, 1998. The effects of lesions, receptor blocking, electrical self-stimulation, and drugs of abuse suggest t...

/pdf/predictive-reward-signal-of-dopamine-neurons-3f94myirza.pdf

Predictive Reward Signal of Dopamine Neurons

http://www.columbia.edu/itc/gsas/g9600/2003/JavitchReadings/Schultz(Sulzer).pdf

Getting Formal with Dopamine and Reward

The basal ganglia: focused selection and inhibition of competing motor programs.

Functional anatomy of the basal ganglia. I. The cortico-basal ganglia-thalamo-cortical loop

The subcortical projections of the centromedian (CM) and the parafascicular (Pf) thalamic nuclei were examined in the squirrel monkey (Saimiri sciureus) by using the lectin Phaseolus vulgaris-leucoagglutinin (PHA-L) as an anterograde tracer. Both CM and Pf project massively to the striatum where they arborize in a complementary fashion. On the one hand, CM innervates most of the putamen caudal to the anterior commissure, a dorsolateral rim of the putamen rostral to the anterior commissure, discrete areas of the head of the caudate nucleus close to the internal capsule, and a lateral sector of the body of the caudate nucleus. On the other hand, Pf provides a heavy input to the head, body, and tail of the caudate nucleus, and to the rostral putamen, excluding the areas innervated by CM. In addition, Pf projects more discretely to the nucleus accumbens and the olfactory tubercle. Therefore, the projections from both CM and Pf cover the entire striatum, with those from CM arborizing into the "sensorimotor" striatal territory and the ones from Pf innervating the "associative-limbic" striatal territory. Furthermore, CM and Pf project to extrastriatal subcortical structures, such as the globus pallidus, the subthalamic nucleus, and the substantia nigra, where they also terminate in a complementary fashion. Topographically and cytologically, Pf is closely related to the subparafascicular nucleus (sPf). The Pf-sPf complex projects to the hypothalamus, the substantia innominata, the peripeduncular nucleus, and the amygdala. It also gives rise to descending efferents arborizing in various brainstem structures, including the inferior olivary complex. Additional studies with retrograde double-labeling methods show that distinct cell groups within CM project to the motor cortex and the striatum. Likewise, separate neuronal populations within the CM-Pf-sPf complex give rise to striatal and brainstem projections, the former arising from CM and Pf and the latter mainly from sPf. The complementary nature of CM and Pf projections to the striatum and other basal ganglia components suggests that this thalamic complex participates in a highly ordered manner in the parallel processing of the information that flows through the basal ganglia.

Efferent connections of the centromedian and parafascicular thalamic nuclei in the squirrel monkey: a PHA-L study of subcortical projections.

The cerebral cortex and the intralaminar thalamic nuclei are the major sources of excitatory glutamatergic afferents to the striatum, whereas the midbrain catecholaminergic neurones provide a dense intrastriatal plexus of dopamine-containing terminals. Evidence from various sources suggests that there is a functional interaction between the glutamate- and dopamine-containing terminals in the striatum. The aim of the present study was to determine the synaptic relationships between cortical or thalamic inputs and the dopaminergic afferents in the sensorimotor territory of the monkey striatum. To address this issue, anterograde tracing in combination with immunocytochemistry for tyrosine hydroxylase (TH) was carried out by light and electron microscopy. Squirrel monkeys received injections of biocytin in the primary motor and somatosensory cortical areas or injections of either Phaseolus vulgaris-leucoagglutinin (PHA-L) or biocytin in the centromedian nucleus (CM) of the thalamus. Sections that included the striatum were processed to visualize the anterograde tracers alone or in combination with TH immunoreactivity. The anterogradely labelled fibres from the cerebral cortex and CM display a band-like pattern and are exclusively confined to the postcommissural region of the putamen, whereas TH-immunoreactive axon terminals are homogeneously distributed throughout the entire extent of the striatum. Electron microscopic analysis revealed that the anterogradely labelled terminals from the cerebral cortex form asymmetric synapses almost exclusively with the heads of dendritic spines. The thalamic terminals also form asymmetric synapses, but in contrast to cortical fibres, predominantly with dendrites (67.4%) and less frequently with spines (32.6%). The TH-immunoreactive boutons are heterogeneous in morphology. The most common type (84% of the total population) forms symmetric synapses; of these the majority is in contact with dendritic shafts (72.1%), less with spines (22.5%) and few with perikarya (5.4%). In sections processed to reveal anterogradely labelled cortical fibres and TH-immunoreactive structures, individual spines of striatal neurones were found to receive convergent synaptic inputs from both cortical and TH-immunoreactive boutons. In contrast, anterogradely labelled thalamic terminals and TH-immunoreactive boutons were never seen to form convergent synaptic contacts on the same postsynaptic structure. These findings suggest that the dopaminergic afferents are located to subserve a more specific modulation of afferent cortical input than afferent thalamic input in the sensorimotor territory of the striatum in primates.

Synaptic relationships between dopaminergic afferents and cortical or thalamic input in the sensorimotor territory of the striatum in monkey.

The organization of the thalamostriatal projections arising from the centromedian (CM) and parafascicular (Pf) thalamic nuclei in the squirrel monkey (Saimiri sciureus) was studied at both light and electron microscopic levels. Following selective injections of the anterograde axonal tracer Phaseolus vulgaris-leucoagglutinin (PHA-L) into the CM or Pf, patterns of terminal arborization within the striatum were compared to the biochemical heterogeneity of the striatum as revealed by immunohistochemical staining for the calcium-binding protein calbindin D-28k (CaBP), and histochemical staining for the enzymes acetylcholinesterase (AChE) and nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-diaphorase). The PHA-L-labeled axon terminals within the striatum were further analyzed at the ultrastructural level to characterize their pattern of synaptic organization. Dense and heterogeneous terminal fields occur in the „sensorimotor” territory of the striatum after CM injections, or in the „associative” striatal territory following Pf injections. In the associative territory labeled axons arborize in a diffuse manner predominantly within areas enriched with CaBP, AChE, or NADPH-diaphorase, representing the matrix compartment, and tend to avoid areas poor in these substances, corresponding to the patch/striosome compartment. In the sensorimotor territory labeled axons form bands that occupy a subregion of the NADPH-diaphorase-rich zone in the putamen. The terminal pattern of the CM-striatal projection suggests the existence of a more complex mosaic organization within the sensorimotor territory. Ultrastructural analysis of PHA-L-labeled elements within the striatum reveals that both CM and Pf projections form asymmetric synapses upon dendrites and spines of striatal cells. A total of 339 PHA-L-labeled boutons were examined after CM injections and compared to 293 boutons following Pf injections. After CM injections, 29% of PHA-L-labeled terminals form synapses on dendritic spines and 66% on dendritic shafts, whereas after Pf injections only 12% of synapses occur on dendritic spines compared to 81% on dendritic shafts. Labeled terminals forming axosomatic or axoaxonic synapses were not seen within the striatum following either CM or Pf injections. It is concluded that in the squirrel monkey: (1) Pf-striatal fibers profusely arborize within the matrix compartment of the associative territory, (2) CM-striatal fibers form bands that occupy a subregion of the NADPH-diaphorase-rich zone within the sensorimotor territory, and (3) that both Pf- and CM-striatal projections establish asymmetric synapses with dendrites and spines of medium-sized spiny cells. These results suggest that the complementary CM and Pf projections to the striatum are in a crucial position to exert a powerful and highly ordered excitatory influence upon the output neurons of the striatum in primates.

Efferent connections of the centromedian and parafascicular thalamic nuclei in the squirrel monkey: a light and electron microscopic study of the thalamostriatal projection in relation to striatal heterogeneity.

Cortical input to parvalbumin-immunoreactive neurones in the putamen of the squirrel monkey

The centre me´dian and parafascicular thalamic nuclei project respectively to the sensorimotor and associative-limbic striatal territories in the squirrel monkey

A. F. Sadikot

Papers

Efferent connections of the centromedian and parafascicular thalamic nuclei in the squirrel monkey: a PHA-L study of subcortical projections.

Synaptic relationships between dopaminergic afferents and cortical or thalamic input in the sensorimotor territory of the striatum in monkey.

Efferent connections of the centromedian and parafascicular thalamic nuclei in the squirrel monkey: a light and electron microscopic study of the thalamostriatal projection in relation to striatal heterogeneity.

Cortical input to parvalbumin-immunoreactive neurones in the putamen of the squirrel monkey

The centre me´dian and parafascicular thalamic nuclei project respectively to the sensorimotor and associative-limbic striatal territories in the squirrel monkey