Neuroscience
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Under normal and dietary iron deficiency conditions, the BXD recombinant inbred (RI) strains of mice show large variations in regional brain iron concentration, particularly in the ventral midbrain (VMB). In a study utilizing just one of the BXD strains, diurnal changes in subregional brain iron concentration were found, which were dependent on the brain region and sex of the mice. The focus of this study was to determine if diurnal changes in VMB can be found across other BXD RI strains and whether a diurnal effect would be common to all strains or variable across strains similar to the large strain variability in iron concentrations determined during the first part of the light phase. ⋯ In conclusion, significant brain-regional-specific diurnal changes in total iron concentrations were found in a selection of BXD RI mice. Sex and strain are functional determinates of which regions will be affected and in what direction the affect will be. The study provides an animal model for future work into determining the biological and genetic basis of circadian influences on VMB iron homeostasis.
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Activation of the dopaminergic mesolimbic reward circuit that originates in the ventral tegmental area (VTA) is postulated to preferentially suppress emotional responses to noxious stimuli, and presumably contributes to the addictive liability of strong analgesics. VTA dopamine neurons are activated via cholinergic afferents and microinjection of carbachol (cholinergic agonist) into VTA is rewarding. Here, we evaluated regional differences within VTA in the capacity of carbachol to suppress rats' affective response to pain (vocalization afterdischarges, VADs) and to support conditioned place preference (CPP) learning. ⋯ The results indicate that analgesia and reward are mediated by separate cholinergic mechanisms within pVTA. Nicotinic receptor antagonism within pVTA failed to attenuate carbachol-induced analgesia, but prevented carbachol-induced reward. As addictive liability of analgesics stem from their rewarding properties, the present findings suggest that these processes can be neuropharmacologically separated within pVTA.
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Purkinje cell (PC) firing represents the sole output from the cerebellar cortex onto the deep cerebellar and vestibular nuclei. Here, we explored the different modes of PC firing in alert mice by extracellular recording. We confirm the existence of a tonic and/or bursting and quiescent modes corresponding to UP and DOWN state, respectively. ⋯ Complex spike (CS) frequency was increased during the 600-Hz buzz, indicating that this PC output actively contributes to the cerebello-olivary loop by triggering a disinhibition of the inferior olive. During the 600-Hz buzz, the first depolarizing component of the CS was reduced and the second depolarizing component was suppressed. Consistent with our experimental observations, using a 559-compartment single-PC model - in which PC UP state (of about -43mV) was obtained by the combined action of large tonic AMPA conductances and counterbalancing GABAergic inhibition - removal of this inhibition produced the 600-Hz buzz; the simulated buzz frequency decreased following an artificial CS.
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Previous studies have shown that patients with Parkinson's disease (PD) experience extensive problems during dual tasking. Up to now, dual-task interference in PD has mainly been investigated in the context of gait research. However, the simultaneous performance of two different tasks is also a prerequisite to efficiently perform many other tasks in daily life, including upper limb tasks. ⋯ In addition, there was a larger dual-task effect on the secondary task in PD patients than controls (p=0.025). The writing tests on the writing tablet proved highly correlated to daily life writing as measured by the 'Systematic Screening of Handwriting Difficulties' test (SOS-test) and other manual dexterity tasks, particularly during dual-task conditions. Taken together, these results provide additional insights into the motor control of handwriting and the effects of dual tasking during upper limb movements in patients with PD.
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Early life stress can permanently alter functioning of the hypothalamic-pituitary-adrenal (HPA) axis, which regulates the stress response and influences the perception of pain. Chronic pelvic pain patients commonly report having experienced childhood neglect or abuse, which increases the likelihood of presenting with comorbid chronic pain and/or mood disorders. Animal models of neonatal stress commonly display enhanced anxiety-like behaviors, colorectal hypersensitivity, and disruption of proper neuro-immune interactions in adulthood. ⋯ Peripherally, NMS and VBD affected the expression of inflammatory mediators in the vagina and bladder. Corticotropin-releasing factor (CRF) receptor and transient receptor potential (TRP) channel protein expression was also significantly, and differentially, affected in vagina, bladder, and colon by both NMS and VBD. Together these data indicate that NMS affects both central and peripheral aspects of the HPA axis, which may drive changes in vaginal sensitivity and the development of comorbid chronic pain and mood disorders.