Review
Leading tonically active neurons of the striatum from reward detection to context recognition

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Tonically active neurons (TANs) in the primate striatum, which are presumed to be cholinergic interneurons, carry signals that are traditionally considered to be important for reward-related learning. Recent studies investigating the functional properties of TANs in behaving monkeys have shown that other factors beyond motivation can affect their responsiveness. There is now evidence that TAN responses reflect stimulus detection, movement control and recognition of a specific context, suggesting that these local circuit neurons contribute to different computations used in learning and action functions of the striatum. This is consistent with the view that TAN responses could represent an important component of the processes that are responsible for the ability to select the appropriate behavioral response to environmental events.

Introduction

In the stratium, several neuron types have been described according to their morphological and chemical features 1, 2, 3; the function of striatal circuitry has been interpreted mainly in terms of the relatively large population of GABA-containing medium spiny neurons that are the source of striatal efferent projections. Although most theoretical models of striatal function have emphasized a role for output neurons, the various interneuron types are increasingly considered as key determinants of the information-processing operations performed in the striatum. Therefore, to improve our understanding of how local circuit neurons can affect the functioning of the striatum, it would be extremely helpful to establish clear behavioral relationships between these interneurons. At present, only one class of interneurons can be readily identified during single-neuron recordings in the striatum of monkeys performing behavioral tasks. They are referred to as the tonically active neurons or TANs, the nature of which is probably cholinergic, as has been suggested by in vivo intracellular recordings in anesthetized rats 4, 5. The electrophysiological characteristics of TANs are sufficiently distinct to permit recordings to target units belonging to this specific neuron population [6]. Through a better evaluation of the behavioral relationships of TANs, it is hoped that we will gain detailed insights into the role of cholinergic neurotransmission in the processing of information in the striatum 7, 8. Although the earliest studies argued that TANs might have a key role in detecting motivationally relevant events, a number of observations indicate that these neurons can provide information about the nature of the stimuli present, irrespective of whether they are motivationally salient or not [6]. It appears therefore that the role of TANs in behavior applies to a broader range of functions than was previously assumed. In particular, evidence has recently accumulated suggesting that these neurons might participate in the control of movement and the integration of contextual information within striatal networks. This review aims to emphasize new insights into the role of TANs drawn from findings from single-neuron recording studies in behaving monkeys.

Section snippets

A role for TANs in detecting rewarding stimuli

Kimura et al. [9] described for the first time the presence of highly reliable pauses in tonic firing of TANs, in response to stimuli that have acquired an incentive value for the behavior of the animal. Although these activity changes occurred in response to a stimulus that elicits a learned motor reaction towards obtaining reward, they appeared unrelated to movement. Subsequent studies 10, 11, 12 have also found evidence suggesting that the response of TANs can reflect the rewarding nature of

Do TANs report an error in the prediction of reward?

Given the suggestion that TANs might receive reward information from the midbrain DA neurons, there has been much interest in the possible contribution of TANs to reinforcement learning. In particular, it is important to know whether TANs might provide signals necessary for associative learning, such as an error in the prediction of a rewarding outcome [19]. By comparing the responsiveness of TANs and DA neurons to conditioned stimuli and primary reward in an instrumental task using various

TANs are not related to exclusively rewarding stimuli

Early investigations of the response properties of TANs have centered upon their sensitivity to rewarding stimuli. More recent studies have extended these findings by showing that these neurons are also concerned with non-rewarding events, including those that are aversive to the animal 22, 23, 24, 25. Interestingly, our experiments have reported that a distinctly different profile of TAN response is produced as a result of aversive and appetitive stimuli. Indeed, although appetitive stimuli

TANs are sensitive to the temporal predictability of stimuli

TAN responses are generally absent when the reward is delivered in a predictable manner in both instrumental and Pavlovian learning situations [13]. In a series of experiments, we have shown that TANs can change their responsiveness by factoring the temporal structure of successive task events 21, 27. As illustrated in Figure 2, the responsiveness of TANs is markedly enhanced when the time of reward becomes unpredictable, both inside and outside of task context. The sensitivity of TANs to

TANs are under the control of contextual factors

A different role has been proposed by Shimo and Hikosaka [32] who have observed, in monkeys performing an oculomotor task, that the sensitivity of TANs for a particular target location in space varies with the reward schedule: their sensitivity is stronger, when only one direction of eye movement is rewarded, than when all directions were rewarded. This demonstrates that TAN responses are not tied to the rewarding properties of the stimulus that initiated the movement, but to the spatial

Do TANs contribute to the generation of action?

It is generally assumed that TAN responses to conditioned stimuli reflect the motivational value of stimuli rather than their motor significance. However, even if TANs are considered to be relatively isolated from motor processes, there is now evidence that they might contribute to the initiation and control of movement. Blazquez et al. [23] have drawn a particular emphasis on the fact that TAN responses to a conditioned stimulus are linked to the immediate behavioral reaction induce by this

Conclusion

Although changes in activity of TANs have been most extensively studied in the context of reward processing and associative learning, increasing attention has been paid to the role of these neurons in other aspects of behavior. The responses of TANs to environmental events are far more varied and complex than previously thought, and it becomes apparent that a motivational interpretation of TAN functioning is not sufficient to reveal their contribution to the control of goal-directed behavior.

Acknowledgements

The experiments were conducted together with E. Legallet, S. Ravel and P. Sardo. I thank anonymous referees for the extensive comments that helped improve the manuscript. The work was supported by the Centre National de la Recherche Scientifique and by grants from the European Commission and the French Ministère de la Recherche et de la Technologie.

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