Alain R. Marchand

Pavlovian to instrumental transfer: a neurobehavioural perspective.

Pavlovian-to-instrumental transfer (PIT) is a key concept in developing our understanding of cue-controlled behaviours. Here we have reviewed the literature on behavioural and neurobiological factors that influence PIT. Meta-analyses of the data for individual groups in PIT studies revealed that PIT is related to both the order and amounts of instrumental and Pavlovian training, and that it is critically determined by competition between instrumental and Pavlovian responses. We directly addressed the role of response competition in PIT in two experiments which showed that extensive Pavlovian conditioning produced more Pavlovian magazine visits and weaker PIT than moderate Pavlovian conditioning (Experiment 1); and that PIT lost after extensive Pavlovian conditioning was restored by Pavlovian extinction training (Experiment 2). These findings confirm that response competition is indeed an important determinant of PIT. This has significant implications for lesion and inactivation studies that assess the neurobiological substrates of PIT, as well as attempts to demonstrate PIT in the drug self-administration paradigm where the effect is yet to be reliably shown.

Discrete Visual Samples May Control Locomotor Equilibrium and Foot Positioning in Man

The static or dynamic visual cues required for equilibrium as well as for foot guidance in visually guided locomotion in man were studied using a variety of locomotion supports and illumination and visual conditions. Stroboscopic illumination (brief flashes) and intermittent lighting (longer flashes) were used to control and to vary the visual sampling frequency of static (positional/orientational) visual cues. There were three main findings: First, visual control of foot positioning during locomotion over a narrow support depends mainly upon the availability of high frequency static visual cues (up to about 12 Hz); and third, static visual cues required for equilibrium control are extracted from both the peripheral and the central visual field. Assuming that discrete demands for feedback occur, a simple probabilistic model was proposed, according to which the mean time that elapses following presentation of static visual cues about positions or changes of position accounts for the differences in the difficulty of the various illumination conditions.

Parallel Maturation of Goal-Directed Behavior and Dopaminergic Systems during Adolescence

Adolescence is a crucial developmental period characterized by specific behaviors reflecting the immaturity of decision-making abilities. However, the maturation of precise cognitive processes and their neurobiological correlates at this period remain poorly understood. Here, we investigate whether a differential developmental time course of dopamine (DA) pathways during late adolescence could explain the emergence of particular executive and motivational components of goal-directed behavior. First, using a contingency degradation protocol, we demonstrate that adolescent rats display a specific deficit when the causal relationship between their actions and their consequences is changed. When the rats become adults, this deficit disappears. In contrast, actions of adolescents remain sensitive to outcome devaluation or to the influence of a pavlovian-conditioned stimulus. This aspect of cognitive maturation parallels a delayed development of the DA system, especially the mesocortical pathway involved in action adaptation to rule changes. Unlike in striatal and nucleus accumbens regions, DA fibers and DA tissue content continue to increase in the medial prefrontal cortex from juvenile to adult age. Moreover, a sustained overexpression of DA receptors is observed in the prefrontal region until the end of adolescence. These findings highlight the relationship between the emergence of specific cognitive processes, in particular the adaptation to changes in action consequences, and the delayed maturation of the mesocortical DA pathway. Similar developmental processes in humans could contribute to the adolescent vulnerability to the emergence of several psychiatric disorders characterized by decision-making deficits.

Transient role of the rat prelimbic cortex in goal-directed behaviour

Lesion studies show that goal‐directed actions mediated by action‐outcome (A‐O) associations and habits mediated by stimulus‐response (S‐R) associations can be dissociated during instrumental training, with the prelimbic region of the medial prefrontal cortex being involved in the former and the infralimbic region in the latter. The present work further investigates the role of the prelimbic region in acquisition vs. expression of goal‐directed instrumental behaviour, using reversible neuronal inactivation and outcome devaluation procedures. In a first experiment, inactivating the prelimbic cortex at the time of testing did not alter the sensitivity to devaluation, indicating that this region was not essential for the expression of A‐O associations. In a second experiment, the prelimbic cortex was inactivated throughout the training phase. At the time of testing the performance was insensitive to devaluation, indicating that the acquired response was not goal‐directed but mediated by an S‐R association. These data challenge the view that the habit system replaces the goal‐directed system as training progresses. They show that the prelimbic cortex plays a transient but crucial role in the acquisition of goal‐directed responding and that the A‐O and S‐R systems can operate in a competitive fashion early in training.

A statistical approach to sensorimotor strategies: conjugate cross-correlations.

A simple method, based on cross-correlation functions (CCFs) between two time series of kinematic or physiological measurements, is proposed for the analysis of multisegmental movements. Special emphasis is placed on measuring accelerations. When the movements of two body segments are coordinated but consistently time lagged, their CCF displays a peak at the corresponding time abscissa. The reproducible positions of the peaks reflect biomechanical or physiological constraints. Several significantly large peaks can be observed in a CCF. It is possible to identify coordinated movements involving more than two segments by applying simple rules of compatibility between the time lags and between the signs of the correlation peaks. With the method proposed, it is possible to determine the signs of relative variation and the time lags of the successive statistically correlated segmental movements. This is particularly useful in the case of both continuous and periodic sensorimotor control, where classical poststimulus methods cannot be applied. Unlike the classical poststimulus methods, this method does not require a time origin, and it is not necessary to monitor the muscles or even to specify exactly which ones are involved. The method is also applicable to experiments involving a time origin (e.g., and applied perturbation), although in this case it is less accurate than the averaging technique. Individual postural strategies can be identified, which suggests some interesting potential applications of the method to clinical studies.

A Cholinergic-Dependent Role for the Entorhinal Cortex in Trace Fear Conditioning

Trace conditioning is considered a model of higher cognitive involvement in simple associative tasks. Studies of trace conditioning have shown that cortical areas and the hippocampal formation are required to associate events that occur at different times. However, the mechanisms that bridge the trace interval during the acquisition of trace conditioning remain unknown. In four experiments with fear conditioning in rats, we explored the involvement of the entorhinal cortex (EC) in the acquisition of fear under a trace-30 s protocol. We first determined that pretraining neurotoxic lesions of the EC selectively impaired trace-, but not delay-conditioned fear as evaluated by freezing behavior. A local cholinergic deafferentation of the EC using 192-IgG-saporin did not replicate this deficit, presumably because cholinergic interneurons were spared by the toxin. However, pretraining local blockade of EC muscarinic receptors with the M1 antagonist pirenzepine yielded a specific and dose-dependent deficit in trace-conditioned responses. The same microinjections performed after conditioning were without effect on trace fear responses. These effects of blocking M1 receptors are consistent with the notion that conditioned stimulus (CS)-elicited, acetylcholine-dependent persistent activities in the EC are needed to maintain a representation of a tone CS across the trace interval during the acquisition of trace conditioning. This function of the EC is consistent with recent views of this region as a short-term stimulus buffer.

Differential contribution of dorsal and ventral hippocampus to trace and delay fear conditioning.

Trace conditioning relies on the maintained representation of a stimulus across a trace interval, and may involve a persistent trace of the conditioned stimulus (CS) and/or a contribution of contextual conditioning. The role of hippocampal structures in these two types of conditioning was studied by means of pretraining lesions and reversible inactivation of the hippocampus in rats. Similar levels of conditioning to a tone CS and to the context were obtained with a trace interval of 30 s. Neurotoxic lesions of the whole hippocampus or reversible muscimol inactivation of the ventral hippocampus impaired both contextual and tone freezing in both trace‐ and delay‐conditioned rats. Dorsal hippocampal injections impaired contextual freezing and trace conditioning, but not delay conditioning. No dissociation between trace and contextual conditioning was observed under any of these conditions. Altogether, these data indicate that the ventral and dorsal parts of the hippocampus compute different aspects of trace conditioning, with the ventral hippocampus being involved in fear and anxiety processes, and the dorsal hippocampus in the temporal and contextual aspects of event representation.

A Role for Medial Prefrontal Dopaminergic Innervation in Instrumental Conditioning

To investigate the involvement of dopaminergic projections to the prelimbic and infralimbic cortex in the control of goal-directed responses, a first experiment examined the effect of pretraining 6-OHDA lesions of these cortices. We used outcome devaluation and contingency degradation procedures to separately assess the representation of the outcome as a goal or the encoding of the contingency between the action and its outcome. All groups acquired the instrumental response at a normal rate, indicating that dopaminergic activity in the medial prefrontal cortex is not necessary for the acquisition of instrumental learning. Sham-operated animals showed sensitivity to both outcome devaluation and contingency degradation. Animals with dopaminergic lesions of the prelimbic cortex, but not the infralimbic cortex, failed to adapt their instrumental response to changes in contingency, whereas their response remained sensitive to outcome devaluation. In a second experiment, aimed at determining whether dopamine was specifically needed during contingency changes, we performed microinfusions of the dopamine D1/D2 receptor antagonist flupenthixol in the prelimbic cortex only before contingency degradation sessions. Animals with infusions of flupenthixol failed to adapt their response to changes in contingency, thus replicating the deficit of animals with dopaminergic lesions in Experiment 1. These results demonstrate that dissociable neurobiological mechanisms support action–outcome relationships and goal representation, dopamine signaling in the prelimbic cortex being necessary for the former but not the latter.

Inhibitory Effects of L‐Glutamate on Central Processes of Crustacean Leg Motoneurons

In crustaceans, glutamatergic excitation at the neuromuscular synapse has been extensively studied. Fewer reports exist of the central and possibly inhibitory actions of glutamate on neurons. The present study analyses the response of intracellularly identified motoneurons, which innervate the proximal leg muscles, to local glutamate pressure applications in the neuropil, in an in vitro thoracic preparation of the crayfish Procambarus clarkii. L‐Glutamate application always inhibited motoneuron activity, with a decrease in input resistance. The resulting depolarization or hyperpolarization could usually be reversed within 10 mV of the resting potential. The response persisted in neurons pharmacologically isolated with Cd2+ or tetrodotoxin. The reversal potential of the response to glutamate was displaced in a low‐chloride solution. Similar responses were obtained with GABA. Application of GABA blocked the glutamate response in a competitive manner. Both responses were suppressed by β‐guanidino‐propionic acid, a competitive antagonist for GABA receptors. This indicates that glutamate activates a chloride‐GABA receptor‐channel. Micromolar concentrations of picrotoxin reduced both the L‐glutamate and the GABA inhibitory responses, thereby unmasking a smaller, picrotoxin‐resistant effect of glutamate (but not of GABA), which was excitatory and sensitive to 6,7‐dinitroquinoxaline‐2,3‐dione (DNQX). These results suggest dual and opposite roles for motoneuron glutamatergic connections–a peripheral (well known) net excitatory one and a central net inhibitory one. Direct inhibition of motoneurons by L‐glutamatergic neurons is to be expected.

Juvenile Obesity Enhances Emotional Memory and Amygdala Plasticity through Glucocorticoids

In addition to metabolic and cardiovascular disorders, obesity is associated with adverse cognitive and emotional outcomes. Its growing prevalence during adolescence is particularly alarming since recent evidence indicates that obesity can affect hippocampal function during this developmental period. Adolescence is a decisive period for maturation of the amygdala and the hypothalamic–pituitary–adrenal (HPA) stress axis, both required for lifelong cognitive and emotional processing. However, little data are available on the impact of obesity during adolescence on amygdala function. Herein, we therefore evaluate in rats whether juvenile high-fat diet (HFD)-induced obesity alters amygdala-dependent emotional memory and whether it depends on HPA axis deregulation. Exposure to HFD from weaning to adulthood, i.e., covering adolescence, enhances long-term emotional memories as assessed by odor–malaise and tone–shock associations. Juvenile HFD also enhances emotion-induced neuronal activation of the basolateral complex of the amygdala (BLA), which correlates with protracted plasma corticosterone release. HFD exposure restricted to adulthood does not modify all these parameters, indicating adolescence is a vulnerable period to the effects of HFD-induced obesity. Finally, exaggerated emotional memory and BLA synaptic plasticity after juvenile HFD are alleviated by a glucocorticoid receptor antagonist. Altogether, our results demonstrate that juvenile HFD alters HPA axis reactivity leading to an enhancement of amygdala-dependent synaptic and memory processes. Adolescence represents a period of increased susceptibility to the effects of diet-induced obesity on amygdala function.