The basal ganglia, especially the circuits originating from the putamen, are essential for controlling normal body movements. Notably, the putamen receives inputs not only from motor cortical areas but also from multiple sensory cortices. However, how these sensory signals are processed in the putamen remains unclear. We recorded the activity of tentative medium spiny neurons in the caudal part of the putamen when the monkey viewed many fractal objects. We found many neurons that responded to these objects, mostly in the ventral region. We called this region putamen tail (PUTt), as it is dorsally adjacent to caudate tail (CDt). Although PUTt and CDt are mostly separated by a thin layer of white matter, their neurons shared several features. Almost all of them had receptive fields in the contralateral hemifield. Moreover, their responses were object selective (i.e., variable across objects). The object selectivity was higher in the ventral region (i.e., CDt > PUTt). Some neurons above PUTt, which we called the caudal-dorsal putamen (cdPUT), also responded to objects, but less selectively than PUTt. Next, we examined whether these visual neurons changed their responses based on the reward outcome. We found that many neurons encoded the values of many objects based on long-term memory, but not based on short-term memory. Such stable value responses were stronger in PUTt and CDt than in cdPUT. These results suggest that PUTt, together with CDt, controls saccade/attention among objects with different historical values, and may control other motor actions as well.SIGNIFICANCE STATEMENT Although the putamen receives inputs not only from motor cortical areas but also from sensory cortical areas, how these sensory signals are processed remains unclear. Here we found that neurons in the caudal-ventral part of the putamen (putamen tail) process visual information including spatial and object features. These neurons discriminate many objects, first by their visual features and later by their reward values as well. Importantly, the value discrimination was based on long-term memory, but not on short-term memory. These results suggest that the putamen tail controls saccade/attention among objects with different historical values and might control other motor actions as well. Many visual objects are attached with values which were created by our long rewarding history. Such stable object values attract gaze. We previously found that the output pathway of basal ganglia from caudal-dorsal-lateral portion of substantia nigra pars reticulata (cdlSNr) to superior colliculus (SC) carries robust stable value signal to execute the automatic choice of valuable objects. An important question here is whether stable value signal in basal ganglia can influence on other inner processing such as perception, attention, emotion, or arousal than motor execution. The key brain circuit is another output path of basal ganglia: the pathway from SNr to temporal and frontal lobes through thalamus. To examine the existence of stable value signal in this pathway, we explored thalamus in a wide range. We found that many neurons in the medial thalamus represented stable value. Histological examination showed that the recorded sites of those neurons included ventral anterior nucleus, pars magnocellularis (VAmc) which is the main target of nigrothalamic projection. Consistent with the SNr GABArgic projection, the latency of value signal in the medial thalamus was later than cdlSNr, and the sign of value coding in the medial thalamus was opposite to cdlSNr. As is the case with cdlSNr neurons, the medial thalamus neurons showed no sensitivity to frequently updated value (flexible value). These results suggest that the pathway from cdlSNr to the medial thalamus influences on various aspects of cognitive processing by propagating stable value signal to the wide cortical area. Direct and indirect pathways in the basal ganglia work together for controlling behavior. However, it is still a controversial topic whether these pathways are segregated or merged with each other. To address this issue, we studied the connections of these two pathways in the caudal parts of the basal ganglia of rhesus monkeys using anatomical tracers. Our previous studies showed that the caudal basal ganglia control saccades by conveying long-term values (stable values) of many visual objects toward the superior colliculus. In experiment 1, we injected a tracer in the caudate tail (CDt), and found local dense plexuses of axon terminals in the caudal-dorsal-lateral part of substantia nigra pars reticulata (cdlSNr) and the caudal-ventral part of globus pallidus externus (cvGPe). These anterograde projections may correspond to the direct and indirect pathways, respectively. To verify this in experiment 2, we injected different tracers into cdlSNr and cvGPe, and found many retrogradely labeled neurons in CDt and, in addition, the caudal-ventral part of the putamen (cvPut). These cdlSNr-projecting and cvGPe-projecting neurons were found intermingled in both CDt and cvPut (which we call striatum tail). A small but significant proportion of neurons (<15%) were double-labeled, indicating that they projected to both cdlSNr and cvGPe. These anatomical results suggest that stable value signals (good vs. bad) are sent from the striatum tail to cdlSNr and cvGPe in a biased (but not exclusive) manner. These connections may play an important role in biasing saccades toward higher valued objects and away from lower valued objects. A prominent target of the basal ganglia is the superior colliculus (SC) which controls gaze orientation (saccadic eye movement in primates) to an important object. This 'object choice' is crucial for choosing an action on the object. SC is innervated by the substantia nigra pars reticulata (SNr) which is controlled mainly by the caudate nucleus (CD). This CD-SNr-SC circuit is sensitive to the values of individual objects and facilitates saccades to good objects. The object values are processed differently in two parallel circuits: flexibly by the caudate head (CDh) and stably by the caudate tail (CDt). To choose good objects, we need to reject bad objects. In fact, these contrasting functions are accomplished by the circuit originating from CDt: The direct pathway focuses on good objects and facilitates saccades to them; the indirect pathway focuses on bad objects and suppresses saccades to them. Inactivation of CDt deteriorated the object choice, because saccades to bad objects were no longer suppressed. This suggests that the indirect pathway is important for object choice. However, the direct and indirect pathways for 'object choice', which aim at the same action (i.e., saccade), may not work for 'action choice'. One possibility is that circuits controlling different actions are connected through the indirect pathway. Additional connections of the indirect pathway with brain areas outside the basal ganglia may also provide a wider range of behavioral choice. In conclusion, basal ganglia circuits are composed of the basic direct/indirect pathways and additional connections and thus have acquired multiple functions.

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Ghazizadeh, Ali; Hong, Simon; Hikosaka, Okihide (2018) Prefrontal Cortex Represents Long-Term Memory of Object Values for Months. Curr Biol 28:2206-2217.e5
Ghazizadeh, Ali; Griggs, Whitney; Leopold, David A et al. (2018) Temporal-prefrontal cortical network for discrimination of valuable objects in long-term memory. Proc Natl Acad Sci U S A 115:E2135-E2144
Griggs, Whitney S; Amita, Hidetoshi; Gopal, Atul et al. (2018) Visual Neurons in the Superior Colliculus Discriminate Many Objects by Their Historical Values. Front Neurosci 12:396
Maeda, Kazutaka; Kunimatsu, Jun; Hikosaka, Okihide (2018) Amygdala activity for the modulation of goal-directed behavior in emotional contexts. PLoS Biol 16:e2005339
Hikosaka, Okihide; Kim, Hyoung F; Amita, Hidetoshi et al. (2018) Direct and indirect pathways for choosing objects and actions. Eur J Neurosci :
Amita, Hidetoshi; Kim, Hyoung F; Smith, Mitchell K et al. (2018) Neuronal connections of direct and indirect pathways for stable value memory in caudal basal ganglia. Eur J Neurosci :
Kim, Hyoung F; Amita, Hidetoshi; Hikosaka, Okihide (2017) Indirect Pathway of Caudal Basal Ganglia for Rejection of Valueless Visual Objects. Neuron 94:920-930.e3
Hikosaka, Okihide; Ghazizadeh, Ali; Griggs, Whitney et al. (2017) Parallel basal ganglia circuits for decision making. J Neural Transm (Vienna) :
Griggs, Whitney S; Kim, Hyoung F; Ghazizadeh, Ali et al. (2017) Flexible and Stable Value Coding Areas in Caudate Head and Tail Receive Anatomically Distinct Cortical and Subcortical Inputs. Front Neuroanat 11:106
Yasuda, Masaharu; Hikosaka, Okihide (2017) To Wait or Not to Wait-Separate Mechanisms in the Oculomotor Circuit of Basal Ganglia. Front Neuroanat 11:35

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