Neural correlates of subjective CS/UCS association in appetitive conditioning

Explicit knowledge of conditioned stimulus (CS)/unconditioned stimulus (UCS) associations is proposed as important factor in classical conditioning. However, while previous studies have focused on its roles in fear conditioning, it has been neglected in the context of appetitive conditioning. The present functional magnetic resonance study aimed to investigate neural activation and functional connectivity linked to subjective CS/UCS association in appetitive conditioning. In total, 85 subjects participated in an appetitive acquisition procedure in which a neutral stimulus (CS+) was paired with a monetary reward, while another neutral stimulus (CS‐) was never paired with the reward. Directly afterwards, subjective CS/UCS association was assessed by measuring the extent to which the CS+ was thought to be associated with the UCS compared to the CS‐. Close relationships were established between subjective CS/UCS association and activations in the primary visual cortex (V1) during the early phase of conditioning and in the striatum during the late conditioning phase. In addition, we observed inverse relationships between subjective CS/UCS association and both V1/ventromedial prefrontal cortex (vmPFC) and striatal/vmPFC connectivity. The results suggest the involvement of decoupling vmPFC connectivity in reward learning in general and the roles of attentional processes in the formation of the subjective CS/UCS association during the early phase and reward prediction during the late phase of appetitive conditioning.     

High cervical lateral spinal cord injury results in long-term ipsilateral hemidiaphragm paralysis

Although axon regeneration is limited in the central nervous system, partial lesions of the spinal cord induce neuroplasticity processes that can lead to spontaneous functional improvement. To determine whether such compensatory mechanisms occur in the respiratory system, we analyzed the incidence of partial injury of the cervical spinal cord on diaphragm activity in adult rats. We show that a section of the lateral area of the C2 cervical spinal cord induces complete phrenic nerve inactivation and ipsilateral hemidiaphragm paralysis, whereas medial or dorsolateral sections had only a moderate effect on respiratory activity. In the case of lateral hemisection, activity of the ipsilateral phrenic nerve was partially restored after a lapse of 3 months. No spontaneous diaphragm recovery was observed, however, even after a lapse of several months in the case of hemisection or lateral section. Ipsilateral hemidiaphragm activity could however be restored after transection of the contralateral phrenic nerve, by activation of the "crossed phrenic phenomenon" (involving activation of previously latent respiratory contralateral pathways crossing the midline). These data suggest that the respiratory system develops important long-term plasticity processes at the level of phrenic motoneuron innervation. However, they do not by themselves allow substantial diaphragm recovery, underscoring the continued need for developing repair strategies. These studies also validates the use of the respiratory system as a model to evaluate the functional incidence of repair strategies not only after hemisection but also after more limited sectioning restricted to the lateral side of the cervical cord.     

Methods for functional magnetic resonance imaging in normal and lesioned behaving monkeys

Methods for performing functional magnetic resonance imaging (fMRI) studies in behaving and lesioned monkeys using a human MR scanner are reported. Materials for head implant surgery were selected based on tests for magnetic susceptibility. A primate chair with a rigid head fixation system and a mock scanner environment for training were developed. To perform controlled visual studies, monkeys were trained to maintain fixation for several minutes using a novel training technique that utilized continuous juice rewards. A surface coil was used to acquire anatomical and functional images in four monkeys, one with a partial lesion of striate cortex. High-resolution anatomical images were used after non-uniform intensity correction to create cortical surface reconstructions of both lesioned and normal hemispheres. Our methods were confirmed in two visual experiments, in which functional activations were obtained during both free viewing and fixation conditions. In one experiment, face-selective activity was found in the fundus and banks of the superior temporal sulcus and the middle temporal gyrus in monkeys viewing pictures of faces and objects while maintaining fixation. In a second experiment, regions in occipital, parietal, and frontal cortex were activated in lesioned and normal animals viewing a cartoon movie. Importantly, in the animal with the striate lesion, fMRI signals were obtained in the immediate vicinity of the lesion. Our results extend those previously reported by providing a detailed account of the technique and by demonstrating the feasibility of fMRI in monkeys with lesions.     

Differential mechanisms and development of leptin resistance in A/J versus C57BL/6J mice during diet-induced obesity

Changes in the biological efficacy of leptin were evaluated in obesity-resistant (A/J) and obesity-prone (C57BL/6J) mice at weaning and after consuming a high-fat (HF) diet for 4 and 8 wk. There was no evidence of leptin resistance in either strain at the start of the study, but after 4 and 8 wk on the HF diet, C57BL/6J mice became unresponsive to ip leptin. C57BL/6J mice responded to intracerebroventricular leptin at these time points but developed peripheral resistance to sympathetic stimulation of retroperitoneal white adipose tissue. In contrast, intracerebroventricular leptin was fully effective in A/J mice, reproducing the complete profile of responses observed in weanling mice. A/J mice were also partially responsive to ip leptin at both time points, increasing uncoupling protein 1 mRNA expression in brown adipose tissue and decreasing leptin mRNA in white adipose tissue. The findings indicate that retention of leptin responsiveness is an important component of the ability of A/J mice to mount a robust adaptive thermogenic response and resist diet-induced obesity.