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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The locus coeruleus (LC) is the major loci of noradrenergic innervation to the forebrain. Due to the extensive central nervous system innervation of the LC noradrenergic system, a reduction in the number of LC neurons could result in significant changes in noradrenergic function in many forebrain regions. LC noradrenergic neurons were lesioned in adult male C57Bl/6 mice with the unilateral administration of 6-hydroxydopamine (6OHDA) (vehicle on the alternate side). ⋯ The loss of LC noradrenergic neurons is associated with reduced NE tissue concentration and NE transporter (NET) binding sites in the frontal cortex and hippocampus, as well as other forebrain regions such as the amygdala and SN. Adrenoreceptor (AR) binding sites (α(1)- and α(2)-AR) were not significantly affected on the 6OHDA-treated side compared to the vehicle-treated side, although there is a reduction of AR binding sites on both the vehicle- and 6OHDA-treated side in specific forebrain regions. These studies indicate that unilateral stereotaxic injection of 6OHDA into mice reduces noradrenergic LC neurons and reduces noradrenergic innervation to many forebrain regions, including the contralateral side.
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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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Histamine in the adult central nervous system (CNS) acts as a neurotransmitter. This amine is one of the first neurotransmitters to appear during development reaching its maximum concentration simultaneously with neuron differentiation peak. This suggests that HA plays an important role in neurogenesis. ⋯ Immunocytochemistry was performed on differentiated cultures to detect mature neurons. To explore the expression of certain important transcriptional factors involved on asymmetric cell division and commitment, RT-PCR and qRT-PCR were performed. Results indicate that HA is required during cell proliferation in order to increase neuron differentiation and suggest that this amine increases neuron commitment during the proliferative phase probably by rising prospero1 and neurogenin1 expression.