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Cerebellar functions are modulated by cholinergic inputs, the density of which varies among cerebellar regions. Although the prepositus hypoglossi nucleus (PHN), a brainstem structure involved in controlling gaze holding, is known as one of the major sources of these cholinergic inputs, the proportions of cholinergic neurons in PHN projections to distinct cerebellar regions have not been quantitatively analyzed. In this study, we identified PHN neurons projecting to the cerebellum by applying retrograde labeling with dextran-conjugated Alexa 488 in choline acetyltransferase (ChAT)-tdTomato transgenic rats and compared the proportion of cholinergic PHN neurons in the PHN projections to four different regions of the cerebellum, namely the flocculus (FL), the uvula and nodulus (UN), lobules III-V in the vermis (VM), and the hemispheric paramedian lobule and crus 2 (PC). In the PHN, the percentage of cholinergic PHN neurons was lower in the projection to the FL than in the projection to the UN, VM or PC. Preposito-cerebellar neurons, except for preposito-FL neurons, included different proportions of cholinergic neurons at different rostrocaudal positions in the PHN. These results suggest that cholinergic PHN neurons project to not only the vestibulocerebellum but also the anterior vermis and posterior hemisphere and that the proportion of cholinergic neurons among projection neurons from the PHN differs depending on cerebellar target areas and the rostro-caudal regions of the PHN. This study provides insights regarding the involvement of cerebellar cholinergic networks in gaze holding.

Learned associations about salient experiences (e.g., drug exposure, stress) and their associated environmental stimuli are mediated by a minority of sparsely distributed, behaviorally activated neurons coined 'neuronal ensembles.' For many years, it was not known whether these neuronal ensembles played causal roles in mediating learned behaviors. However, in the last several years the 'Daun02 inactivation technique' in Fos-lacZ transgenic rats has proved very useful in establishing causal links between neuronal ensembles that express the activity-regulated protein Fos and learned behaviors. Fos-expressing neurons in these rats also express the bacterial protein β-galactosidase (β-gal) in strongly activated neurons. When the prodrug Daun02 is injected into the brains of these rats 90 min after a behavior (e.g., drug-seeking) or cue exposure, then Daun02 is converted into daunorubicin by β-gal, which selectively inactivates Fos- and β-gal-expressing neurons that were activated 90 min before the Daun02 injection. This unit presents protocols for breeding the Fos-lacZ rats and conducting appropriate Daun02 inactivation experiments. © 2016 by John WileySons, Inc.

Major depressive disorder (MDD) is a leading contributor to the global burden of disease. However, the causal relationship of risk factors, such as genetic predisposition or experience of augmented stress, remain unknown. Numerous studies in humans and rodents have implicated brain-derived neurotrophic factor (BDNF) in MDD pathology, as a genetic risk factor and a factor regulated by stress. Until now, the majority of preclinical studies have employed genetically modified mice as their model of choice. However, mice display a limited behavioural repertoire and lack expression of circulating BDNF, which is present in rats and humans. Therefore, heterozygous BDNF (BDNF +/− ) rats were tested for affective behaviours and accompanying expression of key genes associated with affective disorders in the brain. We found that BDNF +/− rats, which have reduced BDNF levels in brain and plasma, displayed symptoms of anhedonia, a core symptom of MDD, and anxiety-like behaviour, but no behavioural despair or cognitive impairments. This was accompanied by changes in the expression of genes that are implicated in modulation of the stress response and affective disorders. Hence, glucocorticoid receptor, neuregulin 1 and disrupted-in-schizophrenia 1 gene expression were upregulated in the prefrontal cortex of BDFN +/− rats, whereas FK506 binding protein 5 levels were decreased in the hippocampus. We conclude that a reduction in BDNF levels alters expression of genes associated with affective disorders, which may contribute to the development of depressive-like symptoms.

As a disease model, the laboratory rat has contributed enormously to neuroscience research over the years. It has also been a popular animal model for Alzheimer's disease but its popularity has diminished during the last decade, as techniques for genetic manipulation in rats have lagged behind that of mice. In recent years, the rat has been making a comeback as an Alzheimer's disease model and the appearance of increasing numbers of transgenic rats will be a welcome and valuable complement to the existing mouse models. This review summarizes the contributions and current status of the rat as an animal model of Alzheimer's disease.

Study objective: We tested the hypothesis where the combined renin-angiotensin system (RAS) and endothelin 1 (ETA) receptor blockade could be more effective in the slowing of progression of CKD wit...

Previous studies have demonstrated that chronic blockade of PDGF receptors prevents the decreases in renal hemodynamic function and renal injury that occur in Cyp1a1-Ren2 transgenic rats with angio...

Objective and background: HLA-B27 transgenic (TG) rats exhibit severe colitis, arthritis and other inflammatory lesions. Previous studies in female TG rats indicate that they develop severe alveolar bone loss (ABL). Lack of data on male TG rats has left open the question of possible hormonal/sex dependence for the observed ABL. The purpose of the present study was to assess the natural history of ABL in male HLA-B27 rats, compared to age- and sex-matched wild-type Fischer 344 (WT) rats. Materials and methods: Fourteen WT and 11 TG male rats, aged 7-8 weeks, were used. Sacrifice times occurred at 10, 22 and 35 weeks. Animal heads were defleshed and treated to remove organic material, and skulls were stained to locate the cemento-enamel junction. ABL was measured as exposed molar root surface area (mm 2 ) on the right maxilla and right mandible. Blinded measurements were performed using a computer-assisted image analysis system. Results: ABL for the entire TG group was significantly different from the WT group (p < 0.05). There was no significant difference in ABL between WT and TG rats at 10 weeks of age. At 22 and 35 weeks of age TG rats experienced 23% and 37% greater ABL than WT rats, respectively; these differences were statistically significant (p < 0.015). For both TG and WT animals, ABL was significantly different between the three age groups. Conclusions: These results, consistent with previous findings in female TG rats, suggest that the accelerated ABL found in TG rats is an adult-onset, age-dependent, and sex-independent process.

We demonstrated that activation of CB1 cannabinoid receptors within the solitary tract nucleus (NTS) of the brainstem via bilateral microinjection of the CB1 agonist CP55,940 modulates baroreflex s...

This work was supported by MICINN (AP2006-04117, BFU2007-60658/BFI, and BFU2009-07793/BFI), Instituto de Salud Carlos III (RETICS RD07/0062/0012, RETICEF RD06/0013/0019), FUNDALUCE, ONCE, Fundacion Medica Mutua Madrilena.

The seventh symposium in the series "Contemporary Topics in Immunology" was held on April 21, 1991, at the FASEB meeting in Atlanta, Georgia. It was sponsored by the National Institute of Allergy and Infectious Diseases, The American Association of Immunologists, and the Clinical Immunology Society. Five topics were discussed by leading researchers in areas of immunology that currently are of exceptional interest and show promise of leading to new advances in the prevention and treatment of human diseases. The topics included: the interactions between immunogenic peptides, class I MHC molecules and T cell receptors; initiation, maintenance, and breakdown of self-tolerance in B lymphocytes; inflammatory disease in HLA-B27 transgenic rats; properties and functions of interleukin-10; and transforming growth factor-beta in reproductive immunology. The exceptional quality of the presentations in this seventh symposium exemplified perfectly the path of basic research that often leads from the laboratory to the clinic.

Alcohol abuse and HIV-1 infection frequently coexist, and these individuals are at high risk for serious lung infections and respiratory failure. Although alcohol ingestion and HIV-1 transgene expression have been shown to independently cause oxidative stress and disrupt alveolar epithelial barrier function in experimental models, their interactive effects have not been examined.In this study, we determined that chronic alcohol ingestion (12 weeks) exacerbated the already significant defects in alveolar epithelial paracellular permeability and lung liquid clearance in HIV-1 transgenic rats. Further, immunocytochemical analyses of tight junction protein expression in primary alveolar epithelial cells showed that occludin and zonula occludens-1 localization within the plasma membrane was more disrupted than in either condition alone, consistent with the observed defects in epithelial barrier function. Interestingly, expression of nuclear factor-erythroid 2-related factor 2 (Nrf2), the transcription factor required to activate the antioxidant-response element, was decreased in primary alveolar epithelial cells isolated from HIV-1 transgenic rats. In parallel, exposing lung epithelial cells in vitro to either alcohol or the HIV-related protein gp120 also decreased Nrf2 expression. Importantly, treatment with procysteine, which increases thiol antioxidants including glutathione, improved tight junction protein localization in the plasma membrane and restored alveolar epithelial barrier function in alcohol-fed HIV-1 transgenic rats.These results provide novel evidence that HIV-related proteins and alcohol together causes more barrier dysfunction in the lung epithelium than either stress alone. However, these significant effects on the alveolar barrier can be mitigated by augmenting the thiol antioxidant pool, a strategy with potential clinical applications in subjects who are highly vulnerable to lung disease because of coexistent alcohol abuse and HIV infection.