Analysis of collateral projections from the lateral orbitofrontal cortex to nucleus accumbens and basolateral amygdala in rats.

The orbitofrontal cortex (OFC) is an important brain area for executive functions. The OFC projects to both the nucleus accumbens (NAc) and the basolateral nucleus of the amygdala (BLA). These two pathways share some similar behavioral functions, but their anatomical and physiological properties have not been compared before. In this study, we first explored the connection of the lateral OFC (lOFC) to NAc core (NAcc) and/or BLA, especially the collateral projections (experiments 1 and 2) with rats. In experiment 1, fluorophore-conjugated retrograde tracers were locally infused into the NAcc and the BLA to sample neurons in the lOFC. Our results revealed that along the anterior-posterior axis of the lOFC, more NAcc- and/or BLA-projecting neurons were distributed toward the posterior end, but the average percentage of collateral projecting neurons at the four sampled lOFC levels remained fairly stable. In experiment 2, antidromic single units in the lOFC responsive to the NAcc and/or the BLA stimulation were identified in anesthetized rats. However, we found that collateral projections from the lOFC to NAcc and BLA were sparse. We next studied the physiological characteristics of these two pathways (experiment 3). In this experiment, orthodromic single units in the NAcc or the BLA responsive to the lOFC stimulation were located in anesthetized rats. Our results showed no difference in the evoked thresholds or the intensity-response probability curves between the two. Together, our results showed that these two pathways were similar in projecting neuron distribution and physiological characteristics.NEW & NOTEWORTHY Using the double retrograde tracing and electrophysiological approach, we reported that among the sampled NAcc- or the BLA-projecting lOFC neurons, the percentage of collateral projections were fairly stable (about 20%-25%) along the lOFC anterior-posterior axis. Furthermore, among the neurons sampled in the NAcc and the BLA, there was no difference in physiological characteristics in response to lOFC stimulation between the two pathways.

Effects of prebiotic consumption on serum intestinal fatty acid-binding protein levels in patients with diabetes: A case-control study.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a condition involving several molecular mechanisms related to the intestinal microbiota for its development. Intestinal fatty acid-binding protein (I-FABP) is a sensitive marker to study enterocyte damage. A prebiotic is a non-digestible food ingredient that improves host health by selectively stimulating the growth and/or activities of bacteria in the colon. We aimed to clarify the currently described effects of prebiotics in the prevention and management of T2DM. METHODS: In this case-control study, we chose 68 participants with T2DM and 52 healthy participants. Both groups were further divided based on consumption of prebiotics. Forty participants with T2DM consumed prebiotics, and 28 did not; 30 healthy volunteers consumed prebiotics, and 22 did not. We used the analysis of variance to compare the inflammation levels between the case and control groups. Multiple linear regression was performed for the significantly correlated groups to estimate the influence of prebiotics on inflammation level. RESULTS: Age was a significant factor for difference in I-FABP levels (standardized coefficient: 0.06; P = .047). The analysis of eating habits showed that vegetarian diets produced lower I-FABP levels than non-vegetarian diets (standardized coefficient: -2.55; P = .022). Results showed that patients with T2DM who consumed prebiotics expressed lower I-FABP levels, reflecting an improvement in inflammation level, than the healthy volunteers who did not consume prebiotics (standardized coefficient: -3.20; P = .019). CONCLUSIONS: For patients with T2DM, prebiotics supplemented produced no significant impact on serum I-FABP levels.

Topiramate suppresses peri-infarct spreading depolarization and improves outcomes in a rat model of photothrombotic stroke.

Ischemic stroke can cause depolarized brain waves, termed peri-infarct depolarization (PID). Here, we evaluated whether topiramate, a neuroprotective drug used to treat epilepsy and alleviate migraine, has the potential to reduce PID. We employed a rat model of photothrombotic ischemia that can reliably and reproducibly induce PID and developed a combined electrocorticography-laser speckle contrast imaging (ECoG-LSCI) platform to monitor neuronal activity and cerebral blood flow (CBF) simultaneously. Topiramate administration after photothrombotic ischemia did not rescue CBF but significantly restored somatosensory evoked potentials in the forelimb area of the primary somatosensory cortex. Moreover, infarct volume was investigated by 2,3,5-triphenyltetrazolium chloride (TTC) staining, and neuronal survival was evaluated by Nissl staining. Mechanistically, the levels of inflammatory markers, such as ED1 (CD68), Iba-1, and GFAP, decreased significantly after topiramate administration, as did BDNF expression, while the expression of NeuN and Bcl-2/Bax increased, which is indicative of reduced inflammation and improved neuroprotection.

Pharmacological activation of the amygdala, but not single prolonged footshock-induced acute stress, interferes with cue-induced motivation toward food rewards in rats.

In the face of threats, animals adapt their behaviors to cope with the situation. Under such circumstances, irrelevant behaviors are usually suppressed. In this study, we examined whether food-seeking motivation would decrease under activation of the amygdala, an important nucleus in the regulation of stress response in the central nervous system, or after a physical acute stress session. In Experiment 1, we pharmacologically activated the basolateral nucleus (BLA) or the central nucleus of the amygdala (CeA) before a cue-induced reinstatement test in rats. Our results showed that activation of the BLA or the CeA abolished cue-induced motivation toward food rewards, while locomotor activity and free food intake were not affected. In Experiments 2 and 3, we further assessed anxiety and despair levels, as well as cue-induced reinstatement, after a single prolonged footshock-induced acute stress in rats. Behaviorally, acute stress did not affect anxiety level, despair level, or cue-induced motivation toward food rewards. Physiologically, there was no difference in cellular activities of the amygdala immediately after acute stress. To conclude, our results suggested that pharmacological activation of the amygdala decreased cue-induced motivation toward food reward. However, physiological acute stress did not immediately interfere with the negative emotions, motivation, or amygdala activities of the animals.

Adaptive anxious states and down-regulation of dopamine activity under amygdala activation in rats.

All individuals face different challenges every day. Under threats, the basolateral nucleus of the amygdala (BLA) is engaged to initiate proper physiological and behavioral responses. In this study, we pharmacologically activated the BLA in rats with no stress history to examine how animals regulated their anxiety- and despair-like behaviors in face of different task demands, as well as their dopamine (DA) activity in ventral tegmental area (VTA). The number of spontaneously firing VTA DA neurons, defined as "population activity", decides the amplitude of DA response to external stimuli, which can be assessed by the behavioral responses of the animals to amphetamine (AMPH) administration; several studies have shown that the level is positively correlated with the AMPH-induced increase in locomotor activity. Our results showed that for anxiety-like behaviors, rats displayed lower anxiety levels in elevated plus maze (EPM) and marble burying test, but increased anxiety level in social interaction test. For despair-like behaviors, there was no difference in performance in the forced swim test (FST) we conducted. Finally, systemic injection of AMPH increased locomotor activity, which was dampened with BLA activation. The inconsistency in anxiety levels in different tasks demonstrated that rats adapted their behavioral strategies to different experimental settings. Together, our results suggested that BLA activation prepared the animals towards different modality of challenges and down-regulated their DA reward system.