In crustaceans, glutamatergic excitation at the neuromuscular synapse has been extensively studie... more 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 beta-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.
Adolescence is a crucial developmental period characterized by specific behaviors reflecting the ... more 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 decisionmaking deficits.
Dopamine release within the nucleus accumbens shell is suggested to control the salience of envir... more Dopamine release within the nucleus accumbens shell is suggested to control the salience of environmental stimuli, and previous research has shown that the indirect dopamine agonist D-amphetamine can alter the salience of both aversive and neutral stimuli. In experiment 1, the effect of systemic injection of D-amphetamine (0.5, 1 mg/kg) on fear conditioning to a tone was assessed in an 'off-baseline' conditioned suppression procedure using several footshock intensities. Although the effects of amphetamine on conditioning were unclear, the results indicated a deficit of simple tone habituation in amphetamine-treated rats. In experiment 2, habituation of the orienting reaction to a tone was assessed by the progressive reduction of lick suppression upon repeated presentation of the auditory stimulus. D-Amphetamine delayed tone habituation, whether administered systemically (0.5, 1 mg/kg) or into the nucleus accumbens shell (3, 10 microg/0.5 microl). These data are consistent with electrophysiological and neurochemical data demonstrating the role of nucleus accumbens dopamine in novelty processing. The relevance of the data to latent inhibition is discussed.
The Journal of neuroscience : the official journal of the Society for Neuroscience, Jan 23, 2015
The orbitofrontal cortex (OFC) is known to play a crucial role in learning the consequences of sp... more The orbitofrontal cortex (OFC) is known to play a crucial role in learning the consequences of specific events. However, the contribution of OFC thalamic inputs to these processes is largely unknown. Using a tract-tracing approach, we first demonstrated that the submedius nucleus (Sub) shares extensive reciprocal connections with the OFC. We then compared the effects of excitotoxic lesions of the Sub or the OFC on the ability of rats to use outcome identity to direct responding. We found that neither OFC nor Sub lesions interfered with the basic differential outcomes effect. However, more specific tests revealed that OFC rats, but not Sub rats, were disproportionally relying on the outcome, rather than on the discriminative stimulus, to guide behavior, which is consistent with the view that the OFC integrates information about predictive cues. In subsequent experiments using a Pavlovian contingency degradation procedure, we found that both OFC and Sub lesions produced a severe defic...
The Journal of neuroscience : the official journal of the Society for Neuroscience, Jan 4, 2015
In addition to metabolic and cardiovascular disorders, obesity is associated with adverse cogniti... more 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 activati...
Structural equation modeling aims at quantifying the strength of causal relationships within a se... more Structural equation modeling aims at quantifying the strength of causal relationships within a set of interacting variables. Although the literature emphasizes that large sample sizes are required, this method is increasingly used with neuroimaging data of a limited number of subjects to study the relationships between cerebral structures. Here, we use a simulation approach to evaluate its ability to provide accurate information under the constraints of neuroimaging.
Please cite this article in press as: Wolff, M., et al., Functional heterogeneity of the limbic t... more Please cite this article in press as: Wolff, M., et al., Functional heterogeneity of the limbic thalamus: From hippocampal to cortical functions. Neurosci. Biobehav. Rev. (2014), http://dx.
Trace conditioning is considered a model of higher cognitive involvement in simple associative ta... more 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.
To investigate the involvement of dopaminergic projections to the prelimbic and infralimbic corte... more 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 D 1 /D 2 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.
Trace conditioning relies on the maintained representation of a stimulus across a trace interval,... more 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. V
In order to select actions appropriate to current needs, a subject must identify relationships be... more In order to select actions appropriate to current needs, a subject must identify relationships between actions and events. Control over the environment is determined by the degree to which action consequences can be predicted, as described by action-outcome contingencies -i.e. performing an action should affect the probability of the outcome. We evaluated in a first experiment adaptation to contingency changes in rats with neurotoxic lesions of the medial prefrontal cortex. Results indicate that this brain region is not critical to adjust instrumental responding to a negative contingency where the rats must refrain from pressing a lever, as this action prevents reward delivery. By contrast, this brain region is required to reduce responding in a non-contingent situation where the same number of rewards is freely delivered and actions do not affect the outcome any more. In a second experiment, we determined that this effect does not result from a different perception of temporal relationships between actions and outcomes since lesioned rats adapted normally to gradually increasing delays in reward delivery. These data indicate that the medial prefrontal cortex is not directly involved in evaluating the correlation between action-and reward-rates or in the perception of reward delays. The deficit in lesioned rats appears to consist of an abnormal response to the balance between contingent and non-contingent rewards. By highlighting the role of prefrontal regions in adapting to the causal status of actions, these data contribute to our understanding of the neural basis of choice tasks.
Pavlovian-to-instrumental transfer (PIT) is a key concept in developing our understanding of cue-... more 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.
Pavlovian fear conditioning in rodents often involves the assessment of freezing behaviour. Since... more Pavlovian fear conditioning in rodents often involves the assessment of freezing behaviour. Since human-based scoring is labourintensive and subject to biases, several automated methods have been proposed, but few of them have been assessed for temporal definition. An accurate method for the automated analysis of freezing in rats is presented. It is based on a comparison of contrast from successive video images (Learn. Mem. 7 (2000) 58). A major improvement involves subtracting a previously recorded image of the empty background from each frame before processing. This simple operation greatly improves reliability, since it cancels the influence of video noise outside the region of interest in the image (the rat), and can also take advantage of the movements of a patterned animal over a textured background. The technique is compared with manual scoring and with the Anagnostaras method in a trace fear conditioning experiment. The method is appropriate to monitor the time course of freezing behaviour. The same system with a different threshold can also score locomotor activity. A quantitative evaluation of the residual errors inherent to automated methods is attempted. #
Structural equation modeling aims at quantifying the strength of causal relationships within a se... more Structural equation modeling aims at quantifying the strength of causal relationships within a set of interacting variables. Although the literature emphasizes that large sample sizes are required, this method is increasingly used with neuroimaging data of a limited number of subjects to study the relationships between cerebral structures. Here, we use a simulation approach to evaluate its ability to provide accurate information under the constraints of neuroimaging.
A simple method, based on cross-correlation functions (CCFs) between two time series of kinematic... more 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.
In crustaceans, glutamatergic excitation at the neuromuscular synapse has been extensively studie... more 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 beta-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.
Adolescence is a crucial developmental period characterized by specific behaviors reflecting the ... more 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 decisionmaking deficits.
Dopamine release within the nucleus accumbens shell is suggested to control the salience of envir... more Dopamine release within the nucleus accumbens shell is suggested to control the salience of environmental stimuli, and previous research has shown that the indirect dopamine agonist D-amphetamine can alter the salience of both aversive and neutral stimuli. In experiment 1, the effect of systemic injection of D-amphetamine (0.5, 1 mg/kg) on fear conditioning to a tone was assessed in an 'off-baseline' conditioned suppression procedure using several footshock intensities. Although the effects of amphetamine on conditioning were unclear, the results indicated a deficit of simple tone habituation in amphetamine-treated rats. In experiment 2, habituation of the orienting reaction to a tone was assessed by the progressive reduction of lick suppression upon repeated presentation of the auditory stimulus. D-Amphetamine delayed tone habituation, whether administered systemically (0.5, 1 mg/kg) or into the nucleus accumbens shell (3, 10 microg/0.5 microl). These data are consistent with electrophysiological and neurochemical data demonstrating the role of nucleus accumbens dopamine in novelty processing. The relevance of the data to latent inhibition is discussed.
The Journal of neuroscience : the official journal of the Society for Neuroscience, Jan 23, 2015
The orbitofrontal cortex (OFC) is known to play a crucial role in learning the consequences of sp... more The orbitofrontal cortex (OFC) is known to play a crucial role in learning the consequences of specific events. However, the contribution of OFC thalamic inputs to these processes is largely unknown. Using a tract-tracing approach, we first demonstrated that the submedius nucleus (Sub) shares extensive reciprocal connections with the OFC. We then compared the effects of excitotoxic lesions of the Sub or the OFC on the ability of rats to use outcome identity to direct responding. We found that neither OFC nor Sub lesions interfered with the basic differential outcomes effect. However, more specific tests revealed that OFC rats, but not Sub rats, were disproportionally relying on the outcome, rather than on the discriminative stimulus, to guide behavior, which is consistent with the view that the OFC integrates information about predictive cues. In subsequent experiments using a Pavlovian contingency degradation procedure, we found that both OFC and Sub lesions produced a severe defic...
The Journal of neuroscience : the official journal of the Society for Neuroscience, Jan 4, 2015
In addition to metabolic and cardiovascular disorders, obesity is associated with adverse cogniti... more 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 activati...
Structural equation modeling aims at quantifying the strength of causal relationships within a se... more Structural equation modeling aims at quantifying the strength of causal relationships within a set of interacting variables. Although the literature emphasizes that large sample sizes are required, this method is increasingly used with neuroimaging data of a limited number of subjects to study the relationships between cerebral structures. Here, we use a simulation approach to evaluate its ability to provide accurate information under the constraints of neuroimaging.
Please cite this article in press as: Wolff, M., et al., Functional heterogeneity of the limbic t... more Please cite this article in press as: Wolff, M., et al., Functional heterogeneity of the limbic thalamus: From hippocampal to cortical functions. Neurosci. Biobehav. Rev. (2014), http://dx.
Trace conditioning is considered a model of higher cognitive involvement in simple associative ta... more 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.
To investigate the involvement of dopaminergic projections to the prelimbic and infralimbic corte... more 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 D 1 /D 2 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.
Trace conditioning relies on the maintained representation of a stimulus across a trace interval,... more 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. V
In order to select actions appropriate to current needs, a subject must identify relationships be... more In order to select actions appropriate to current needs, a subject must identify relationships between actions and events. Control over the environment is determined by the degree to which action consequences can be predicted, as described by action-outcome contingencies -i.e. performing an action should affect the probability of the outcome. We evaluated in a first experiment adaptation to contingency changes in rats with neurotoxic lesions of the medial prefrontal cortex. Results indicate that this brain region is not critical to adjust instrumental responding to a negative contingency where the rats must refrain from pressing a lever, as this action prevents reward delivery. By contrast, this brain region is required to reduce responding in a non-contingent situation where the same number of rewards is freely delivered and actions do not affect the outcome any more. In a second experiment, we determined that this effect does not result from a different perception of temporal relationships between actions and outcomes since lesioned rats adapted normally to gradually increasing delays in reward delivery. These data indicate that the medial prefrontal cortex is not directly involved in evaluating the correlation between action-and reward-rates or in the perception of reward delays. The deficit in lesioned rats appears to consist of an abnormal response to the balance between contingent and non-contingent rewards. By highlighting the role of prefrontal regions in adapting to the causal status of actions, these data contribute to our understanding of the neural basis of choice tasks.
Pavlovian-to-instrumental transfer (PIT) is a key concept in developing our understanding of cue-... more 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.
Pavlovian fear conditioning in rodents often involves the assessment of freezing behaviour. Since... more Pavlovian fear conditioning in rodents often involves the assessment of freezing behaviour. Since human-based scoring is labourintensive and subject to biases, several automated methods have been proposed, but few of them have been assessed for temporal definition. An accurate method for the automated analysis of freezing in rats is presented. It is based on a comparison of contrast from successive video images (Learn. Mem. 7 (2000) 58). A major improvement involves subtracting a previously recorded image of the empty background from each frame before processing. This simple operation greatly improves reliability, since it cancels the influence of video noise outside the region of interest in the image (the rat), and can also take advantage of the movements of a patterned animal over a textured background. The technique is compared with manual scoring and with the Anagnostaras method in a trace fear conditioning experiment. The method is appropriate to monitor the time course of freezing behaviour. The same system with a different threshold can also score locomotor activity. A quantitative evaluation of the residual errors inherent to automated methods is attempted. #
Structural equation modeling aims at quantifying the strength of causal relationships within a se... more Structural equation modeling aims at quantifying the strength of causal relationships within a set of interacting variables. Although the literature emphasizes that large sample sizes are required, this method is increasingly used with neuroimaging data of a limited number of subjects to study the relationships between cerebral structures. Here, we use a simulation approach to evaluate its ability to provide accurate information under the constraints of neuroimaging.
A simple method, based on cross-correlation functions (CCFs) between two time series of kinematic... more 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.
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