Neuroscience
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The underlying mechanisms and involved brain areas in sensory gating of repetitive auditory stimuli remain unclear. Especially, the influence of the auditory cortex and the role of temporal precision are under debate. Our first objective was to analyze gating dynamics of local field potentials in the primary auditory cortex and the ventral striatum in an animal experiment, particularly, assessing the influence of the cortex. ⋯ Furthermore, we also observed a between-area phase unlocking during sound presentations. Phase de-synchronization appears to be the candidate mechanism behind attenuation of responses to identical repetitive stimuli in the ventral striatum. We conclude that a direct inhibitory response suppression by the auditory cortex plays a minor role in this process.
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Here we examined how mu-opioid receptor signaling in the periaqueductal gray (PAG) mediates conditional and unconditional responses to aversive stimuli. The mu-opioid agonist morphine (MOR) and/or the partially mu-selective antagonist naltrexone (NAL) were infused into dorsolateral PAG (dlPAG) during a fear conditioning task, in which rats were trained to fear an auditory conditional stimulus (CS) by pairing it with a unilateral eyelid shock unconditional stimulus (US). During drug-free test sessions, the CS elicited movement suppression responses (indicative of freezing) from trained rats that had not recently encountered the US. ⋯ Infusions of NAL into dlPAG did not affect CS- or US-evoked behavioral responses at the 1x dosage, but impaired CS-evoked movement suppression at the 10x dosage, both in the presence and absence of MOR. When rats were co-infused with MOR and NAL, MOR-induced effects were not reversed by either dosage of NAL, and some measures of MOR-induced movement suppression were enhanced by NAL at the 1x dosage. Based on these findings, we conclude that mu-opioid receptors in dlPAG may selectively regulate descending supraspinal motor pathways that drive active movement behaviors, and that interactions between MOR and NAL in dlPAG may be more complex than simple competition for binding at the mu receptor.
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The spinal Neuropeptide Y (NPY) system is a potential target for development of new pain therapeutics. NPY and two of its receptors (Y1 and Y2) are found in the superficial dorsal horn of the spinal cord, a key area of nociceptive gating and modulation. ⋯ In the present study, we sought to determine the role of dorsal horn Y1R-expressing neurons in pain by destroying them with NPY-sap and testing the rats on three operant tasks. Lumbar intrathecal NPY-sap (1) reduced Complete Freund's Adjuvant (CFA)-induced hyper-reflexia on the 10°C cold plate, (2) reduced cold aversion on the thermal preference and escape tasks, (3) was analgesic to noxious heat on the escape task, (4) reduced the CFA-induced allodynia to cold temperatures experienced on the thermal preference, feeding interference, and escape tasks, and (5) did not inhibit or interfere with morphine analgesia.
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The angiotensin II receptor subtype 2 (AT2-R) has been proposed to mediate protective vascular actions after brain injury. In this study we investigated the participation of this peptide in the tolerance to cellular damage induced by preconditioning in a rat model of neonatal hypoxia-ischemia (HI). We found that injured animals present a decreased number of microvessels in the ipsilateral (IPLT) side of the brain while in the contralateral (CNLT) side the microvessel number is increased. ⋯ However these vessels show a remarkable increase of the fluorescent signal when they are labeled with antiFlk-1 (VEGFR2), while the Flt-1 (VEGFR1) signal faded in both the injured and the preconditioned animals. The pharmacological blockade of the AT2-R by the drug PD123319 (1.69 mM in the lateral ventricle) diminished the resilience of the microvasculature to HI injury provided by preconditioning and also the Flk-1 increase that occurred in these animals. In conclusion these results suggest an interaction of the AT2-R with VEGFR2 in the neonatal brain microvasculature that produces protective effects which are associated with injury tolerance.