An investigation of the neurobiological mechanisms involved in the control of operant behaviour by reinforcers: quantitative studies using the progressive-ratio schedule

This thesis describes a series of experiments investigating the neural underpinnings of the ‘efficacy’ or ‘value’ of food reinforcers in the control of operant behaviour. A number of methods have been devised for measuring reinforcer value. The experiments described in this thesis employed the progressive-ratio schedule, in which the number of responses required to obtain a reinforcer is progressively increased with each successive reinforcer. The performance of rats on this schedule was analysed using a quantitative model of schedule-controlled behaviour, Killeen’s (1994) ‘Mathematical Principles of Reinforcement’ (MPR) model. An advantage of this approach is that MPR provides a theoretical basis for discriminating between the effects of interventions on ‘motivational’ and ‘motor’ aspects of operant behaviour. According to MPR, schedule-controlled behaviour may be characterized by an ‘activation’ parameter, a, which measures the reinforcer efficacy or value, a ‘response time’ parameter, δ, which measures the minimum inter-response time, and a ‘coupling’ parameter’ β which expresses the weight in short-term memory assigned to the most recent response. Chapter 1 reviews the background literature related to the main themes of the project: the neurobiology and behavioural functions of the orexinergic and the dopaminergic systems of the brain, and the use of the progressive-ratio schedule in behavioural neuroscience. Special emphasis is given to MPR and its application to behavioural neuroscience. Experiment 1 (Chapter 2) examined the effect of destruction of orexinergic neurones of the lateral hypothalamic area (LHA), which have been proposed to control reward processes and food intake. Orexinergic neurones were destroyed by intracerebral injection of a selective neurotoxin, the orexin-B-saporin conjugate (OxSap). OxSap-induced lesions had no effect on the parameter a and did not alter food intake. However, they did increase the response time parameter δ, suggesting that the lesion had a motor debilitating effect. Experiment 2 (Chapter 3) investigated the effect of disconnecting the LHA from the ventral tegmental area (VTA), a major area of projection of the orexinergic neurones. Functional disconnection was achieved by unilateral injection of OxSap into the LHA on one side and into the VTA on the contralateral side of the brain. The lesion had no effect on a or any other of the motivational measures used, or on food intake. However δ was increased, suggesting that the lesion mainly affected motor functioning. Since OxSap has a preferential destructive effect on neurones that express the orexin-2 (OX2) receptor, the possibility was considered that the putative role of orexins in regulating reinforcer value may be mediated by orexin-1 (OX1) receptors, rather than OX2 receptors. In order to explore this possibility, Experiment 3 (Chapter 4) examined the effect of acute functional disconnection of the LHA from the nucleus accumbens shell (AcbS), an area rich in OX1 receptors. Disconnection was achieved by unilateral OxSap-induced lesions of the LHA and infusion of the OX1 receptor antagonist, SB-334867-A (1-(2-methylbenzoxazol-6-yl)-3-[1,5]naphthyridin-4-yl-urea hydrochloride) into the contralateral AcbS via indwelling intracerebral cannulae. The results showed a reduction of the activation parameter a, with no effect on any of the other parameters. These findings are consistent with the notion that OX1 receptors are involved in the control of the reinforcer value, whereas the OX2 receptors are more involved in the control of motor-related processes. Experiment 4 (Chapter 5) examined the effect of cyproheptadine, a drug with 5-hydroxytryptamine (5HT2A) and histamine (H1) receptor blocking action. Cyproheptadine’s effect on progressive-ratio schedule performance was compared with the effects of the ‘atypical’ antipsychotic drug clozapine, which shares many of cyproheptadine’s pharmacological actions, and the ‘conventional’ antipsychotic haloperidol, whose principal action is antagonism of D2-like dopamine receptors. In addition, the effects of two drugs with known effects on food intake, Δ9-tetrahydrocannabinol (THC) and chlordiazepoxide, were also examined. Cyproheptadine and clozapine increased both a and δ. Haloperidol reduced a and increased δ and chlordiazepoxide increased a. Unexpectedly, THC had no effect on the parameters of MPR; this negative result was explored further in Experiment 6 (see below). Experiment 5 (Chapter 6) examined the differential involvement of D1-like and D2-like dopamine receptors in the control of progressive-ratio schedule performance reinforced with a sucrose solution or corn oil. Performance maintained by both reinforcers conformed to the equation derived from MPR. Blockade of D2-like receptors by haloperidol equally affected performance maintained by corn oil and sucrose, reducing a and increasing δ. However blockade of D1-like receptors by SKF-83566 (bromo-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3-benzazepin-7-ol hydrobromide) reduced both a and δ in rats trained with the sucrose reinforcer but had no effect on the rats reinforced with corn oil. This is consistent with the notion that D1-like and D2-like dopamine receptors exert differential influences on the values of different kinds of food reinforcer. Experiment 6 (Chapter 7) examined the effect of THC on progressive-ratio schedule performance of rats reinforced with corn oil and sucrose. The rats were tested under food deprived and free feeding conditions. In addition, the effect of THC on food intake was assessed. The results confirmed that THC did not affect any of the parameters of MPR. When the animals were transferred from the food deprived to the free feeding condition they showed a reduction of a but no change of δ. This is in agreement with the assumption of MPR that a and δ are independent parameters. Finally, there was a trend for THC to increase sucrose consumption and to reduce corn oil intake, suggesting that cannabinoid receptors may mediate different effects on the reinforcing values of these two foods. Chapter 8 summarises the results of the experiments from the project, and discusses some of their implications. The implications of the findings of Experiments 1-3 for the role of orexinergic mechanisms in the regulation of reinforcer value and motor processes are discussed. The results of Experiments 4 and 5 are considered in the context of the putative involvement of dopamine receptors in reinforcement processes and the effects of conventional and atypical antipsychotics on motivated behaviour. The failure of THC to affect progressive-ratio schedule performance (Experiments 4 and 6) is discussed in the context of the relationship between reinforcer ‘value’ and food consumption. The general implications of these findings for behavioural pharmacology and MPR are considered. Finally, some futures lines of investigation are proposed

An investigation of the neurobiological mechanisms involved in the control of operant behaviour by reinforcers: quantitative studies using the progressive-ratio schedule

This thesis describes a series of experiments investigating the neural underpinnings of the ‘efficacy’ or ‘value’ of food reinforcers in the control of operant behaviour. A number of methods have been devised for measuring reinforcer value. The experiments described in this thesis employed the progressive-ratio schedule, in which the number of responses required to obtain a reinforcer is progressively increased with each successive reinforcer. The performance of rats on this schedule was analysed using a quantitative model of schedule-controlled behaviour, Killeen’s (1994) ‘Mathematical Principles of Reinforcement’ (MPR) model. An advantage of this approach is that MPR provides a theoretical basis for discriminating between the effects of interventions on ‘motivational’ and ‘motor’ aspects of operant behaviour. According to MPR, schedule-controlled behaviour may be characterized by an ‘activation’ parameter, a, which measures the reinforcer efficacy or value, a ‘response time’ parameter, δ, which measures the minimum inter-response time, and a ‘coupling’ parameter’ β which expresses the weight in short-term memory assigned to the most recent response. Chapter 1 reviews the background literature related to the main themes of the project: the neurobiology and behavioural functions of the orexinergic and the dopaminergic systems of the brain, and the use of the progressive-ratio schedule in behavioural neuroscience. Special emphasis is given to MPR and its application to behavioural neuroscience. Experiment 1 (Chapter 2) examined the effect of destruction of orexinergic neurones of the lateral hypothalamic area (LHA), which have been proposed to control reward processes and food intake. Orexinergic neurones were destroyed by intracerebral injection of a selective neurotoxin, the orexin-B-saporin conjugate (OxSap). OxSap-induced lesions had no effect on the parameter a and did not alter food intake. However, they did increase the response time parameter δ, suggesting that the lesion had a motor debilitating effect. Experiment 2 (Chapter 3) investigated the effect of disconnecting the LHA from the ventral tegmental area (VTA), a major area of projection of the orexinergic neurones. Functional disconnection was achieved by unilateral injection of OxSap into the LHA on one side and into the VTA on the contralateral side of the brain. The lesion had no effect on a or any other of the motivational measures used, or on food intake. However δ was increased, suggesting that the lesion mainly affected motor functioning. Since OxSap has a preferential destructive effect on neurones that express the orexin-2 (OX2) receptor, the possibility was considered that the putative role of orexins in regulating reinforcer value may be mediated by orexin-1 (OX1) receptors, rather than OX2 receptors. In order to explore this possibility, Experiment 3 (Chapter 4) examined the effect of acute functional disconnection of the LHA from the nucleus accumbens shell (AcbS), an area rich in OX1 receptors. Disconnection was achieved by unilateral OxSap-induced lesions of the LHA and infusion of the OX1 receptor antagonist, SB-334867-A (1-(2-methylbenzoxazol-6-yl)-3-[1,5]naphthyridin-4-yl-urea hydrochloride) into the contralateral AcbS via indwelling intracerebral cannulae. The results showed a reduction of the activation parameter a, with no effect on any of the other parameters. These findings are consistent with the notion that OX1 receptors are involved in the control of the reinforcer value, whereas the OX2 receptors are more involved in the control of motor-related processes. Experiment 4 (Chapter 5) examined the effect of cyproheptadine, a drug with 5-hydroxytryptamine (5HT2A) and histamine (H1) receptor blocking action. Cyproheptadine’s effect on progressive-ratio schedule performance was compared with the effects of the ‘atypical’ antipsychotic drug clozapine, which shares many of cyproheptadine’s pharmacological actions, and the ‘conventional’ antipsychotic haloperidol, whose principal action is antagonism of D2-like dopamine receptors. In addition, the effects of two drugs with known effects on food intake, Δ9-tetrahydrocannabinol (THC) and chlordiazepoxide, were also examined. Cyproheptadine and clozapine increased both a and δ. Haloperidol reduced a and increased δ and chlordiazepoxide increased a. Unexpectedly, THC had no effect on the parameters of MPR; this negative result was explored further in Experiment 6 (see below). Experiment 5 (Chapter 6) examined the differential involvement of D1-like and D2-like dopamine receptors in the control of progressive-ratio schedule performance reinforced with a sucrose solution or corn oil. Performance maintained by both reinforcers conformed to the equation derived from MPR. Blockade of D2-like receptors by haloperidol equally affected performance maintained by corn oil and sucrose, reducing a and increasing δ. However blockade of D1-like receptors by SKF-83566 (bromo-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3-benzazepin-7-ol hydrobromide) reduced both a and δ in rats trained with the sucrose reinforcer but had no effect on the rats reinforced with corn oil. This is consistent with the notion that D1-like and D2-like dopamine receptors exert differential influences on the values of different kinds of food reinforcer. Experiment 6 (Chapter 7) examined the effect of THC on progressive-ratio schedule performance of rats reinforced with corn oil and sucrose. The rats were tested under food deprived and free feeding conditions. In addition, the effect of THC on food intake was assessed. The results confirmed that THC did not affect any of the parameters of MPR. When the animals were transferred from the food deprived to the free feeding condition they showed a reduction of a but no change of δ. This is in agreement with the assumption of MPR that a and δ are independent parameters. Finally, there was a trend for THC to increase sucrose consumption and to reduce corn oil intake, suggesting that cannabinoid receptors may mediate different effects on the reinforcing values of these two foods. Chapter 8 summarises the results of the experiments from the project, and discusses some of their implications. The implications of the findings of Experiments 1-3 for the role of orexinergic mechanisms in the regulation of reinforcer value and motor processes are discussed. The results of Experiments 4 and 5 are considered in the context of the putative involvement of dopamine receptors in reinforcement processes and the effects of conventional and atypical antipsychotics on motivated behaviour. The failure of THC to affect progressive-ratio schedule performance (Experiments 4 and 6) is discussed in the context of the relationship between reinforcer ‘value’ and food consumption. The general implications of these findings for behavioural pharmacology and MPR are considered. Finally, some futures lines of investigation are proposed

Perirhinal cortex lesions impair tests of object recognition memory but spare novelty detection

This article is protected by copyright. All rights reserved. Acknowledgements This work was supported by the Wellcome Trust (WT103722/Z/14/Z). The authors wish to thank L. Kinnavane and J. M. Pearce for their contributions to the manuscript. The authors confirm that they have no known conflicts of interest.Peer reviewedPublisher PD

Effect of orexin-B-saporin-induced lesions of the lateral hypothalamus on performance on a progressive ratio schedule

It has been suggested that a sub-population of orexinergic neurones whose somata lie in the lateral hypothalamic area (LHA) play an important role in regulating the reinforcing value of both food and drugs. This experiment examined the effect of disruption of orexinergic mechanisms in the LHA on performance on the progressive-ratio schedule of reinforcement, in which the response requirement increases progressively for successive reinforcers. The data were analysed using a mathematical model which yields a quantitative index of reinforcer value and dissociates effects of interventions on motor and motivational processes (Killeen, 1994). Rats were trained under a progressive-ratio schedule using food-pellet reinforcement. They received bilateral injections of conjugated orexin-B-saporin (OxSap) into the LHA or sham lesions. Training continued for a further 40 sessions after surgery. Equations were fitted to the response rate data from each rat, and the parameters of the model were derived for successive blocks of 10 sessions. The OxSap lesion reduced the number of orexin-containing neurones in the LHA by approximately 50% compared to the sham-lesioned group. The parameter expressing the incentive value of the reinforcer was not significantly altered by the lesion. However, the parameter related to the maximum response rate was significantly affected, suggesting that that motor capacity was diminished in the OxSap-lesioned group. The results indicate that OxSap lesions of the LHA disrupted food-reinforced responding on the progressive-ratio schedule. It is suggested that this disruption was brought about by a change in non-motivational (motor) processes

Perirhinal cortex lesions in rats: Novelty detection and sensitivity to interference

Rats with perirhinal cortex lesions received multiple object recognition trials within a continuous session to examine whether they show false memories. Experiment 1 focused on exploration patterns during the first object recognition test postsurgery, in which each trial contained 1 novel and 1 familiar object. The perirhinal cortex lesions reduced time spent exploring novel objects, but did not affect overall time spent exploring the test objects (novel plus familiar). Replications with subsequent cohorts of rats (Experiments 2, 3, 4.1) repeated this pattern of results. When all recognition memory data were combined (Experiments 1–4), giving totals of 44 perirhinal lesion rats and 40 surgical sham controls, the perirhinal cortex lesions caused a marginal reduction in total exploration time. That decrease in time with novel objects was often compensated by increased exploration of familiar objects. Experiment 4 also assessed the impact of proactive interference on recognition memory. Evidence emerged that prior object experience could additionally impair recognition performance in rats with perirhinal cortex lesions. Experiment 5 examined exploration levels when rats were just given pairs of novel objects to explore. Despite their perirhinal cortex lesions, exploration levels were comparable with those of control rats. While the results of Experiment 4 support the notion that perirhinal lesions can increase sensitivity to proactive interference, the overall findings question whether rats lacking a perirhinal cortex typically behave as if novel objects are familiar, that is, show false recognition. Rather, the rats retain a signal of novelty but struggle to discriminate the identity of that signal

Activation of Ventral Tegmental Area 5-HT2C Receptors Reduces Incentive Motivation

FUNDING AND DISCLOSURE The research was funded by Wellcome Trust (WT098012) to LKH; and National Institute of Health (DK056731) and the Marilyn H. Vincent Foundation to MGM. The University of Michigan Transgenic Core facility is partially supported by the NIH-funded University of Michigan Center for Gastrointestinal Research (DK034933). The remaining authors declare no conflict of interest. ACKNOWLEDGMENTS We thank Dr Celine Cansell, Ms Raffaella Chianese and the staff of the Medical Research Facility for technical assistance. We thank Dr Vladimir Orduña for the scientific advice and technical assistance.Peer reviewedPublisher PD

XVI International Congress of Control Electronics and Telecommunications: "Techno-scientific considerations for a post-pandemic world intensive in knowledge, innovation and sustainable local development"

Este título, sugestivo por los impactos durante la situación de la Covid 19 en el mundo, y que en Colombia lastimosamente han sido muy críticos, permiten asumir la obligada superación de tensiones sociales, políticas, y económicas; pero sobre todo científicas y tecnológicas. Inicialmente, esto supone la existencia de una capacidad de la sociedad colombiana por recuperar su estado inicial después de que haya cesado la perturbación a la que fue sometida por la catastrófica pandemia, y superar ese anterior estado de cosas ya que se encontraban -y aún se encuentran- muchos problemas locales mal resueltos, medianamente resueltos, y muchos sin resolver: es decir, habrá que rediseñar y fortalecer una probada resiliencia social existente - producto del prolongado conflicto social colombiano superado parcialmente por un proceso de paz exitoso - desde la tecnociencia local; como lo indicaba Markus Brunnermeier - economista alemán y catedrático de economía de la Universidad de Princeton- en su libro The Resilient Society…La cuestión no es preveerlo todo sino poder reaccionar…aprender a recuperarse rápido.This title, suggestive of the impacts during the Covid 19 situation in the world, and which have unfortunately been very critical in Colombia, allows us to assume the obligatory overcoming of social, political, and economic tensions; but above all scientific and technological. Initially, this supposes the existence of a capacity of Colombian society to recover its initial state after the disturbance to which it was subjected by the catastrophic pandemic has ceased, and to overcome that previous state of affairs since it was found -and still is find - many local problems poorly resolved, moderately resolved, and many unresolved: that is, an existing social resilience test will have to be redesigned and strengthened - product of the prolonged Colombian social conflict partially overcome by a successful peace process - from local technoscience; As Markus Brunnermeier - German economist and professor of economics at Princeton University - indicates in his book The Resilient Society...The question is not to foresee everything but to be able to react...learn to recover quickly.Bogot

An investigation of the neurobiological mechanisms involved in the control of operant behaviour by reinforcers : quantitative studies using the progressive-ratio schedule

This thesis describes a series of experiments investigating the neural underpinnings of the ‘efficacy’ or ‘value’ of food reinforcers in the control of operant behaviour. A number of methods have been devised for measuring reinforcer value. The experiments described in this thesis employed the progressive-ratio schedule, in which the number of responses required to obtain a reinforcer is progressively increased with each successive reinforcer. The performance of rats on this schedule was analysed using a quantitative model of schedule-controlled behaviour, Killeen’s (1994) ‘Mathematical Principles of Reinforcement’ (MPR) model. An advantage of this approach is that MPR provides a theoretical basis for discriminating between the effects of interventions on ‘motivational’ and ‘motor’ aspects of operant behaviour. According to MPR, schedule-controlled behaviour may be characterized by an ‘activation’ parameter, a, which measures the reinforcer efficacy or value, a ‘response time’ parameter, δ, which measures the minimum inter-response time, and a ‘coupling’ parameter’ β which expresses the weight in short-term memory assigned to the most recent response. Chapter 1 reviews the background literature related to the main themes of the project: the neurobiology and behavioural functions of the orexinergic and the dopaminergic systems of the brain, and the use of the progressive-ratio schedule in behavioural neuroscience. Special emphasis is given to MPR and its application to behavioural neuroscience. Experiment 1 (Chapter 2) examined the effect of destruction of orexinergic neurones of the lateral hypothalamic area (LHA), which have been proposed to control reward processes and food intake. Orexinergic neurones were destroyed by intracerebral injection of a selective neurotoxin, the orexin-B-saporin conjugate (OxSap). OxSap-induced lesions had no effect on the parameter a and did not alter food intake. However, they did increase the response time parameter δ, suggesting that the lesion had a motor debilitating effect. Experiment 2 (Chapter 3) investigated the effect of disconnecting the LHA from the ventral tegmental area (VTA), a major area of projection of the orexinergic neurones. Functional disconnection was achieved by unilateral injection of OxSap into the LHA on one side and into the VTA on the contralateral side of the brain. The lesion had no effect on a or any other of the motivational measures used, or on food intake. However δ was increased, suggesting that the lesion mainly affected motor functioning. Since OxSap has a preferential destructive effect on neurones that express the orexin-2 (OX2) receptor, the possibility was considered that the putative role of orexins in regulating reinforcer value may be mediated by orexin-1 (OX1) receptors, rather than OX2 receptors. In order to explore this possibility, Experiment 3 (Chapter 4) examined the effect of acute functional disconnection of the LHA from the nucleus accumbens shell (AcbS), an area rich in OX1 receptors. Disconnection was achieved by unilateral OxSap-induced lesions of the LHA and infusion of the OX1 receptor antagonist, SB-334867-A (1-(2-methylbenzoxazol-6-yl)-3-[1,5]naphthyridin-4-yl-urea hydrochloride) into the contralateral AcbS via indwelling intracerebral cannulae. The results showed a reduction of the activation parameter a, with no effect on any of the other parameters. These findings are consistent with the notion that OX1 receptors are involved in the control of the reinforcer value, whereas the OX2 receptors are more involved in the control of motor-related processes. Experiment 4 (Chapter 5) examined the effect of cyproheptadine, a drug with 5-hydroxytryptamine (5HT2A) and histamine (H1) receptor blocking action. Cyproheptadine’s effect on progressive-ratio schedule performance was compared with the effects of the ‘atypical’ antipsychotic drug clozapine, which shares many of cyproheptadine’s pharmacological actions, and the ‘conventional’ antipsychotic haloperidol, whose principal action is antagonism of D2-like dopamine receptors. In addition, the effects of two drugs with known effects on food intake, Δ9-tetrahydrocannabinol (THC) and chlordiazepoxide, were also examined. Cyproheptadine and clozapine increased both a and δ. Haloperidol reduced a and increased δ and chlordiazepoxide increased a. Unexpectedly, THC had no effect on the parameters of MPR; this negative result was explored further in Experiment 6 (see below). Experiment 5 (Chapter 6) examined the differential involvement of D1-like and D2-like dopamine receptors in the control of progressive-ratio schedule performance reinforced with a sucrose solution or corn oil. Performance maintained by both reinforcers conformed to the equation derived from MPR. Blockade of D2-like receptors by haloperidol equally affected performance maintained by corn oil and sucrose, reducing a and increasing δ. However blockade of D1-like receptors by SKF-83566 (bromo-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3-benzazepin-7-ol hydrobromide) reduced both a and δ in rats trained with the sucrose reinforcer but had no effect on the rats reinforced with corn oil. This is consistent with the notion that D1-like and D2-like dopamine receptors exert differential influences on the values of different kinds of food reinforcer. Experiment 6 (Chapter 7) examined the effect of THC on progressive-ratio schedule performance of rats reinforced with corn oil and sucrose. The rats were tested under food deprived and free feeding conditions. In addition, the effect of THC on food intake was assessed. The results confirmed that THC did not affect any of the parameters of MPR. When the animals were transferred from the food deprived to the free feeding condition they showed a reduction of a but no change of δ. This is in agreement with the assumption of MPR that a and δ are independent parameters. Finally, there was a trend for THC to increase sucrose consumption and to reduce corn oil intake, suggesting that cannabinoid receptors may mediate different effects on the reinforcing values of these two foods. Chapter 8 summarises the results of the experiments from the project, and discusses some of their implications. The implications of the findings of Experiments 1-3 for the role of orexinergic mechanisms in the regulation of reinforcer value and motor processes are discussed. The results of Experiments 4 and 5 are considered in the context of the putative involvement of dopamine receptors in reinforcement processes and the effects of conventional and atypical antipsychotics on motivated behaviour. The failure of THC to affect progressive-ratio schedule performance (Experiments 4 and 6) is discussed in the context of the relationship between reinforcer ‘value’ and food consumption. The general implications of these findings for behavioural pharmacology and MPR are considered. Finally, some futures lines of investigation are proposed.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Contrasting networks for recognition memory and recency memory revealed by immediate-early gene imaging in the rat

The expression of the immediate-early gene c-fos was used to compare networks of activity associated with recency memory (temporal order memory) and recognition memory. In Experiment 1, rats were first familiarized with sets of objects and then given pairs of different, familiar objects to explore. For the recency test group, each object in a pair was separated by 110 min in the time between their previous presentations. For the recency control test, each object in a pair was separated by less than a 1 min between their prior presentations. Temporal discrimination of the objects correlated with c-fos activity in the recency test group in several sites, including area Te2, the perirhinal cortex, lateral entorhinal cortex, as well as the dentate gyrus, hippocampal fields CA3 and CA1. For both the test and control conditions, network models were derived using structural equation modeling. The recency test model emphasized serial connections from the perirhinal cortex to lateral entorhinal cortex and then to the CA1 subfield. The recency control condition involved more parallel pathways, but again highlighted CA1 within the hippocampus. Both models contrasted with those derived from tests of object recognition (Experiment 2), because stimulus novelty was associated with pathways from the perirhinal cortex to lateral entorhinal cortex that then involved both the dentate gyrus (and CA3) and CA1 in parallel. The present findings implicate CA1 for the processing of familiar stimuli, including recency discriminations, while the dentate gyrus and CA3 pathways are recruited when the perirhinal cortex signals novel stimuli

Medial temporal pathways for contextual learning:Network c-fos mapping in rats with or without perirhinal cortex lesions

In the rat brain, context information is thought to engage network interactions between the postrhinal cortex, medial entorhinal cortex, and the hippocampus. In contrast, object information is thought to be more reliant on perirhinal cortex and lateral entorhinal cortex interactions with the hippocampus. The ‘context network’ was explored by mapping expression of the immediate-early gene, c-fos, after exposure to a new spatial environment. Structural equation modelling of Fos counts produced networks of good fit that closely matched prior predictions based on anatomically-grounded functional models. These same models did not, however, fit the Fos data from home-cage controls nor did they fit the corresponding data from a previous study exploring object recognition. These additional analyses highlight the specificity of the context network. The home-cage controls, meanwhile, showed raised levels of inter-area Fos correlations between the many sites examined, i.e., their changes in Fos levels lacked anatomical specificity. Two additional groups of rats received perirhinal cortex lesions. While the loss of perirhinal cortex reduced lateral entorhinal c-fos activity, it did not affect mean levels of hippocampal c-fos expression. Likewise, overall c-fos expression in the prelimbic cortex, retrosplenial cortex and nucleus reuniens of the thalamus appeared unaffected by the perirhinal cortex lesions. Nevertheless, the perirhinal cortex lesions disrupted network interactions involving the medial entorhinal cortex and the hippocampus, highlighting ways in which perirhinal cortex might affect specific aspects of context learning