Michel Goillandeau

Shaping of motor responses by incentive values through the basal ganglia.

The striatum is a key neural interface for cognitive and motor information processing in which associations between reward value and visual stimulus can be used to modify motor commands. It can guide action–selection processes that occur farther downstream in the basal ganglia (BG) circuit, by encoding the reward value of an action. Here, we report on the study of simultaneously recorded neurons in the dorsal striatum (input stage of the BG) and the internal pallidum (output stage of the BG) in two monkeys performing a center-out motor task in which the visual targets were associated with different reward probabilities. We show that the tuning curves of motor-related neurons in both structures are modulated by the value of the action before movement initiation and during its execution. The representations of values associated with different actions change dynamically during the task in the internal globus pallidus, with a significant increase in the number of encoding neurons for the chosen target at the onset of movement. This report sheds additional light on the functional differences between the input and output structures of the BG and supports the assertion that the dorsal basal ganglia are involved in movement-related decision-making processes based on incentive values.

Altered pallido‐pallidal synaptic transmission leads to aberrant firing of globus pallidus neurons in a rat model of Parkinson's disease

•  We used optogenetics approach to characterize the short‐term plasticity of striato‐pallidal (STR–GP) and pallido‐pallidal (GP–GP) GABAergic synapses in rat brain slices. •  We show that only GP–GP (and not STR–GP) transmission is augmented by chronic dopamine depletion. •  Finally, we report that altered GP–GP synaptic transmission promotes neuronal synchronization and rebound bursting in globus pallidus neurons. •  Our results support the conclusion that maladaptive GP–GP GABAergic transmission is likely to be a key underlying factor of the pathological activity in the globus pallidus observed in Parkinsons disease.

A challenging task for assessment of checking behaviors in obsessive-compulsive disorder

Objective:  The present study concerns the objective and quantitative measurement of checking activity, which represents the most frequently observed compulsions in obsessive–compulsive disorder (OCD). To address this issue, we developed an instrumental task producing repetitive checking in OCD subjects.

Neuronal activity correlated with checking behaviour in the subthalamic nucleus of patients with obsessive–compulsive disorder

Doubt, and its behavioural correlate, checking, is a normal phenomenon of human cognition that is dramatically exacerbated in obsessive-compulsive disorder. We recently showed that deep brain stimulation in the associative-limbic area of the subthalamic nucleus, a central core of the basal ganglia, improved obsessive-compulsive disorder. To understand the physiological bases of symptoms in such patients, we recorded the activity of individual neurons in the therapeutic target during surgery while subjects performed a cognitive task that gave them the possibility of unrestricted repetitive checking after they had made a choice. We postulated that the activity of neurons in this region could be influenced by doubt and checking behaviour. Among the 63/87 task-related neurons recorded in 10 patients, 60% responded to various combinations of instructions, delay, movement or feedback, thus highlighting their role in the integration of different types of information. In addition, task-related activity directed towards decision-making increased during trials with checking in comparison with those without checking. These results suggest that the associative-limbic subthalamic nucleus plays a role in doubt-related repetitive thoughts. Overall, our results not only provide new insight into the role of the subthalamic nucleus in human cognition but also support the fact that subthalamic nucleus modulation by deep brain stimulation reduced compulsive behaviour in patients with obsessive-compulsive disorder.

Noradrenergic modulation of intrinsic and synaptic properties of lumbar motoneurons in the neonatal rat spinal cord.

Although it is known that noradrenaline (NA) powerfully controls spinal motor networks, few data are available regarding the noradrenergic (NAergic) modulation of intrinsic and synaptic properties of neurons in motor networks. Our work explores the cellular basis of NAergic modulation in the rat motor spinal cord. We first show that lumbar motoneurons express the three classes of adrenergic receptors at birth. Using patch-clamp recordings in the newborn rat spinal cord preparation, we characterized the effects of NA and of specific agonists of the three classes of adrenoreceptors on motoneuron membrane properties. NA increases the motoneuron excitability partly via the inhibition of a KIR like current. Methoxamine (α1), clonidine (α2) and isoproterenol (β) differentially modulate the motoneuron membrane potential but also increase motoneuron excitability, these effects being respectively inhibited by the antagonists prazosin (α1), yohimbine (α2) and propranolol (β). We show that the glutamatergic synaptic drive arising from the T13-L2 network is enhanced in motoneurons by NA, methoxamine and isoproterenol. On the other hand, NA, isoproterenol and clonidine inhibit both the frequency and amplitude of miniature glutamatergic EPSCs while methoxamine increases their frequency. The T13-L2 synaptic drive is thereby differentially modulated from the other glutamatergic synapses converging onto motoneurons and enhanced by presynaptic α1 and β receptor activation. Our data thus show that the NAergic system exerts a powerful and complex neuromodulation of lumbar motor networks in the neonatal rat spinal cord.

Electrophysiological Correlates of a Versatile Executive Control System in the Monkey Anterior Cingulate Cortex

When a subject faces conflicting situations, decision-making becomes uncertain. The human dorsal anterior cingulate cortex (dACC) has been repeatedly implicated in the monitoring of such situations, and its neural activity is thought to be involved in behavioral adjustment. However, this hypothesis is mainly based on neuroimaging results and is challenged by animal studies that failed to report any neuronal correlates of conflict monitoring. This discrepancy is thought be due either to methodological or more fundamental cross-species differences. In this study, we eliminated methodological biases and recorded single-neuron activity in monkeys performing a Stroop-like task. We found specific changes in dACC activity during incongruent trials but only in a small subpopulation of cells. Critically, these changes were not related to reaction time and were absent before any incorrect action was taken. A larger fraction of neurons exhibited sustained activity during the whole decision period, whereas another subpopulation of neurons was modulated by reaction time, with a gradual increase in their firing rate that peaked at movement onset. Most of the neurons found in these subpopulations exhibited activity after the delivery of an external negative feedback stimulus that indicated an error had been made. These findings, which are consistent with an executive control role, reconcile various theories of prefrontal cortex function and support the homology between human and monkey cognitive architectures.

The globus pallidus pars interna in goal-oriented and routine behaviors: Resolving a long-standing paradox

There is an apparent contradiction between experimental data showing that the basal ganglia are involved in goal‐oriented and routine behaviors and clinical observations. Lesion or disruption by deep brain stimulation of the globus pallidus interna has been used for various therapeutic purposes ranging from the improvement of dystonia to the treatment of Tourettes syndrome. None of these approaches has reported any severe impairment in goal‐oriented or automatic movement.

Single medial prefrontal neurons cope with error.

Learning from mistakes is a key feature of human behavior. However, the mechanisms underlying short-term adaptation to erroneous action are still poorly understood. One possibility relies on the modulation of attentional systems after an error. To explore this possibility, we have designed a Stroop-like visuo-motor task in monkeys that favors incorrect action. Using this task, we previously found that single neurons recorded from the anterior cingulate cortex (ACC) were closely tuned to behavioral performance and, more particularly, that the activity of most neurons was biased towards the evaluation of erroneous action. Here we describe single neurons engaged in both error detection and response alertness processing, whose activation is closely associated with the improvement of subsequent behavioral performance. Specifically, we show that the effect of a warning stimulus on neuronal firing is enhanced after an erroneous response rather than a successful one and that this outcome is correlated with an error rate decrease. Our results suggest that the anterior cingulate cortex, which exhibits this activity, serves as a powerful computational locus for rapid behavioral adaptation.

Easy Rider: Monkeys Learn to Drive a Wheelchair to Navigate through a Complex Maze

The neurological bases of spatial navigation are mainly investigated in rodents and seldom in primates. The few studies led on spatial navigation in both human and non-human primates are performed in virtual, not in real environments. This is mostly because of methodological difficulties inherent in conducting research on freely-moving monkeys in real world environments. There is some incertitude, however, regarding the extrapolation of rodent spatial navigation strategies to primates. Here we present an entirely new platform for investigating real spatial navigation in rhesus monkeys. We showed that monkeys can learn a pathway by using different strategies. In these experiments three monkeys learned to drive the wheelchair and to follow a specified route through a real maze. After learning the route, probe tests revealed that animals successively use three distinct navigation strategies based on i) the place of the reward, ii) the direction taken to obtain reward or iii) a cue indicating reward location. The strategy used depended of the options proposed and the duration of learning. This study reveals that monkeys, like rodents and humans, switch between different spatial navigation strategies with extended practice, implying well-conserved brain learning systems across different species. This new task with freely driving monkeys provides a good support for the electrophysiological and pharmacological investigation of spatial navigation in the real world by making possible electrophysiological and pharmacological investigations.

Checking behavior in rhesus monkeys is related to anxiety and frontal activity

When facing doubt, humans can go back over a performed action in order to optimize subsequent performance. The present study aimed to establish and characterize physiological doubt and checking behavior in non-human primates (NHP). We trained two rhesus monkeys (Macaca mulatta) in a newly designed “Check-or-Go” task that allows the animal to repeatedly check and change the availability of a reward before making the final decision towards obtaining that reward. By manipulating the ambiguity of a visual cue in which the reward status is embedded, we successfully modulated animal certainty and created doubt that led the animals to check. This voluntary checking behavior was further characterized by making EEG recordings and measuring correlated changes in salivary cortisol. Our data show that monkeys have the metacognitive ability to express voluntary checking behavior similar to that observed in humans, which depends on uncertainty monitoring, relates to anxiety and involves brain frontal areas.