Neuroscience
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Acetylcholine (ACh) acts through nicotinic and muscarinic ACh receptors in the ventral midbrain and striatal areas to influence dopamine (DA) transmission. This cholinergic control of DA transmission is important for processes such as attention and motivated behavior, and is manipulated by nicotine in tobacco products. Identifying and characterizing the key ACh receptors involved in cholinergic control of DA transmission could lead to small molecule therapeutics for treating disorders involving attention, addiction, Parkinson's disease, and schizophrenia. α6-Containing nicotinic acetylcholine receptors (nAChRs) are highly and specifically expressed in midbrain DA neurons, making them an attractive drug target. ⋯ To complement these behavioral studies, we studied the ability of in vivo α6(∗) nAChR activation to support plasticity changes in midbrain DA neurons that are relevant to behavioral sensitization and addiction. By coupling local infusion of drugs and brain slice patch-clamp electrophysiology, we show that activating α6(∗) nAChRs in midbrain DA areas is sufficient to enhance glutamatergic transmission in ventral tegmental area (VTA) DA neurons. Together, these results from in vivo studies strongly suggest that α6(∗) nAChRs expressed by VTA DA neurons are positioned to strongly influence both DA-mediated behaviors and the induction of synaptic plasticity by nicotine.
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Spinal 5-HT3 receptor (5-HT3R) has been implicated in chronic pain development. The extent to which 5-HT3R contributes to spinal sensitization and diabetic neuropathic pain (DNP) remains elusive and the mechanisms subserving the effects of 5-HT3R activation on spinal pain processing during chronic pain are still unclear. In this study, we evaluated the contribution of spinal 5-HT3R to pain facilitation and spinal sensitization during DNP, exploiting the role of GABAAR-mediated neurotransmission and glial activation in the effects elicited by intrathecal administration of a 5-HT3R antagonist. ⋯ The spinal activation of GABAAR by i.t. administration of muscimol abolished Y25130-driven antinociception. The expression of IBA-1, GFAP and 5-HT3R was unaltered by treatment. These findings point to a GABA-mediated pronociceptive role of spinal 5-HT3R during DNP.
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Studies on sound perception show a tendency to overestimate the distance of an approaching sound source, leading to a faster reaction time compared to a receding sound source. Nevertheless, it is unclear whether motor preparation and execution change according to the perceived sound direction and distance, particularly when the sound falls inside the individual's peripersonal space. In this study we developed several auditory stimuli by means of two speakers, generating sounds moving toward the perceiver but stopping at different distances from her/him. ⋯ Results showed that action initiation was anticipated as a function of sound distance: the closer the sound, the earlier the movement onset, when the sound entered the subject's peripersonal space. Less error for distance estimation was present when the sound was inside the peripersonal space with a modulation in the order of a few centimeters. Overall, our results reveal a link between perceptual bias in sound distance evaluation and peripersonal space, suggesting the presence of motor plan specificity.
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Prolonged neuronal depression after spreading depression (SD) is followed by a late cellular and synaptic hyperexcitability. Intra- and extracellular recordings of bioelectrical activities were performed in the rodent hippocampus to investigate the role of γ-aminobutyric acid (GABA)-mediated inhibition in the late hyperexcitable state of SD. The effect of KCl-induced negative DC potential shifts was investigated on extracellularly recorded paired-pulse depression (PPD) and bicuculline-induced afterdischarges as well as intracellularly recorded inhibitory post synaptic potentials (IPSPs) in the hippocampal CA1 area. ⋯ Application of low concentrations of bicuculline before the induction of SD enhanced the inhibitory effect of SD on IPSPs. Data indicate the contribution of GABA-mediated inhibition to SD-induced delayed hyperexcitability. Modulation of GABA function in the late hyperexcitability phase of SD may play a role in therapeutic management of SD-related neurological disorders.
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The blood-brain barrier (BBB) is formed by the endothelial cells with specialized tight junctions (TJs) lining the blood vessels and astroglial endfeet surrounding the blood vessels. Although BBB disruption during brain insults leads to vasogenic edema as one of the primary steps in the epileptogenic process, little is known about the molecular and physiological events concerning vasogenic edema formation. ⋯ Indeed, BQ788 (an ETB receptor antagonist) effectively attenuated SE-induced vasogenic edema by inhibiting eNOS-mediated MMP-9 activation and ZO-1 protein degradation in endothelial cells, although astroglial endfeet were detached from endothelial cells. Therefore, we suggest that SE-induced ETB receptor/eNOS-mediated MMP-9 activation may lead to impairments of endothelial cell function via TJ protein degradation, which are involved in vasogenic edema formation independent of perivascular astroglial functions.