Basal forebrain and prelimbic cortex connectivity is related to behavioral response in an attention task.

The basal forebrain (BF) is critical for the motivational recruitment of attention in response to reward-related cues. This finding is consistent with a role for the BF in encoding and transmitting motivational salience and readying prefrontal circuits for further attentional processing. We recorded local field potentials to determine connectivity between prelimbic cortex (PrL) and BF during the modulation of attention by reward-related cues. We find that theta and gamma power are robustly associated with behavior. Power in both bands is significantly lower during trials in which an incorrect behavioral response is made. We find strong coherence during responses that are significantly stronger when a correct response is made. We show that information flow is largely monodirectional from BF to and is strongest when correct responses are made. These experiments demonstrate that connectivity between BF and the PrL increases during periods of increased motivational recruitment of attentional resources.

Maternal immune activation alters the sequential structure of ultrasonic communications in male rats.

Maternal immune activation (MIA) is a risk factor for schizophrenia and many of the symptoms and neurodevelopmental changes associated with this disorder have been modelled in the rodent. While several previous studies have reported that rodent ultrasonic vocalizations (USVs) are affected by MIA, no previous study has examined whether MIA affects the way that individual USVs occur over time to produce vocalisation sequences. The sequential aspect of this behaviour may be particularly important because changes in sequencing mechanisms have been proposed as a core deficit in schizophrenia. The present research generates MIA with POLY I:C administered to pregnant Sprague-Dawley rat dams at GD15. Male pairs of MIA adult offspring or pairs of their saline controls were placed into a two-chamber apparatus where they were separated from each other by a perforated plexiglass barrier. USVs were recorded for a period of 10 â€‹min and automated detection and call review were used to classify short call types in the nominal 50 â€‹kHz band of social affiliative calls. Our data show that the duration of these 50-kHz USVs is longer in MIA rat pairs and the time between calls is shorter. Furthermore, the transition probability between call pairs was different in the MIA animals compared to the control group, indicating alterations in sequential behaviour. These results provide the first evidence that USV call sequencing is altered by the MIA intervention and suggest that further investigations of these temporally extended aspects of USV production are likely to reveal useful information about the mechanisms that underlie sequence generation. This is particularly important given previous research suggesting that sequencing deficits may have a significant impact on both behaviour and cognition.

Basal Forebrain Mediates Motivational Recruitment of Attention by Reward-Associated Cues.

The basal forebrain, composed of distributed nuclei, including substantia innominata (SI), nucleus basalis and nucleus of the diagonal band of Broca plays a crucial neuromodulatory role in the brain. In particular, its projections to the prefrontal cortex have been shown to be important in a wide variety of brain processes and functions, including attention, learning and memory, arousal, and decision-making. In the present study, we asked whether the basal forebrain is involved in recruitment of cognitive effort in response to reward-related cues. This interaction between motivation and cognition is critically impacted in psychiatric conditions such as schizophrenia. Using the Designer Receptor Exclusively Activated by Designer Drug (DREADD) technique combined with our recently developed signaled probability sustained attention task (SPSA), which explicitly assays the interaction between motivation and attention, we sought to determine the role of the basal forebrain in this interaction. Rats were stereotaxically injected in the basal forebrain with either hM4D(Gi) (a virus that expresses receptors which silence neurons in the presence of the drug clozapine-N-oxide; CNO) or a control virus and tested in the SPSA. Behavior of rats during baseline and under saline indicated control by reward probability. In the presence of CNO, differential accuracy of hM4D(Gi) rats on high and low reward-probability trials was abolished. This result occurred despite spared ability of the reward-probability signals to differentially impact choice-response latencies and omissions. These results indicate that the basal forebrain is critical for the motivational recruitment of attention in response to reward-related cues and are consistent with a role for basal forebrain in encoding and transmitting motivational salience of reward-related cues and readying prefrontal circuits for further attentional processing.

Evaluation of mechanism for antihypertensive and vasorelaxant effects of hexanic and hydroalcoholic extracts of celery seed in normotensive and hypertensive rats

ABSTRACT Celery (Apium graveolens L., Apiaceae) is one of the popular aromatic vegetables and part of the daily diet around the world. In this study, aqueous-ethanolic and hexane extracts of celery seed were prepared and the amount of n-butylphthalide, as an active component, was determined in each extract. Then the effects of hexanic extract on systolic, diastolic, mean arterial blood pressure and heart rate were evaluated in an invasive rat model. The vasodilatory effect and possible mechanisms of above mentioned extracts on aorta ring were also measured. High performance liquid chromatography analysis revealed that hexanic extract contains significantly higher amounts of n-butylphthalide, compared to aqueous-ethanolic extract. The results indicated that hexanic extract significantly decreased the systolic, diastolic, mean arterial blood pressure and heart rate in normotensive and hypertensive rats. Our data revealed that celery seed extract exerts its hypotensive effects through its bradycardic and vasodilatory properties. Moreover, the active components in celery seed extracts could induce their vasodilatory properties through Ca2+ channel blocking activity in endothelial and non-endothelial pathways and particularly by interference with the extra or intracellular calcium.

Protective and hypoglycemic effects of celery seed on streptozotocin-induced diabetic rats: experimental and histopathological evaluation.

AIMS: Diabetes mellitus is a major manifestation of metabolic disorder which presents with hyperglycemia (high levels of serum blood sugar). In the present study, we aimed to investigate the effects of celery seed extract on different biochemical factors and histopathological changes in normal and streptozotocin (STZ)-induced diabetic rats. METHODS: A total of 35 male Wistar rats were divided into five groups (one normal and four diabetic groups). STZ was injected intraperitoneally to induce diabetes. The effects of hexane extract of celery seed and glibenclamide (as a positive control) were compared. Blood samples were analyzed on days 0, 18, and 33, and histopathological evaluations were performed at the end of the study. RESULTS: Glucose, triglycerides, and cholesterol levels significantly decreased, whereas insulin and high-density lipoprotein (HDL) levels increased in the extract-administered groups, as compared to the negative diabetic control group (P < 0.0001). The concentrations of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum of the extract-administered groups were significantly less than the negative control group (P < 0.0001). Histopathological reports revealed significantly less atrophy, necrosis, and inflammation in the rats receiving celery seed extract compared to the negative control group. CONCLUSIONS: The results indicated that celery seed extract can be effective in controlling hyperglycemia and hyperlipidemia in diabetic rats, and demonstrated its protective effects against pancreatic toxicity resulting from STZ-induction.

Development of ocular drug delivery systems using molecularly imprinted soft contact lenses.

Recently, significant advances have been made in order to optimize drug delivery to ocular tissues. The main problems in ocular drug delivery are poor bioavailability and uncontrollable drug delivery of conventional ophthalmic preparations (e.g. eye drops). Hydrogels have been investigated since 1965 as new ocular drug delivery systems. Increase of hydrogel loading capacity, optimization of drug residence time on the ocular surface and biocompatibility with the eye tissue has been the main focus of previous studies. Molecular imprinting technology provided the opportunity to fulfill the above-mentioned objectives. Molecularly imprinted soft contact lenses (SCLs) have high potentials as novel drug delivery systems for the treatment of eye disorders. This technique is used for the preparation of polymers with specific binding sites for a template molecule. Previous studies indicated that molecular imprinting technology could be successfully applied for the preparation of SCLs as ocular drug delivery systems. Previous research, particularly in vivo studies, demonstrated that molecular imprinting is a versatile and effective method in optimizing the drug release behavior and enhancing the loading capacity of SCLs as new ocular drug delivery systems. This review highlights various potentials of molecularly imprinted contact lenses in enhancing the drug-loading capacity and controlling the drug release, compared to other ocular drug delivery systems. We have also studied the effects of contributing factors such as the type of comonomer, template/functional monomer molar ratio, crosslinker concentration in drug-loading capacity, and the release properties of molecularly imprinted hydrogels.

Crocetin attenuates spatial learning dysfunction and hippocampal injury in a model of vascular dementia.

Chronic cerebral hypoperfusion produces brain ischemia and is associated with related memory impairment. In this study, we prepared crocetin from crocin (the main water soluble pigment in saffron stigmas) in an acidic hydrolysis and its purity was evaluated using spectrophotometry, thin layer chromatography (TLC) and high performance liquid chromatography (HPLC). The memory enhancing effect of crocetin was then studied in a rat model of chronic cerebral hypoperfusion. Different doses of crocetin were administered intraperitoneally (i.p.). The spatial learning and memory function were tested using Morris water maze, after permanent occlusion of common carotids. Finally, the animals were euthanatized in CO2 chamber and histopathological changes in cerebral cortex and hippocampus were investigated. The results indicated that the escape latency time significantly decreased in crocetin treated rats, in comparison with control animals. Also, the percentage of time spent and traveled distance in target quadrant on final test trial day increased in crocetin 8 mg/kg group, compared to control group, while no difference was observed between groups in swimming speed. All behavioral results were confirmed by histopathological analysis. According to our data, crocetin (8 mg/kg) could properly protect cerebrocortical and hippocampus neurons against ischemia. In conclusion, treatment with crocetin could effectively prevent neuropathological alterations in hippocampus thereby resulting in improvement of spatial learning memory in rats after chronic cerebral hypoperfusion.