Neuroscience
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Although ionotropic glutamate receptors and nicotinic receptors for acetylcholine (ACh) have usually been studied separately, they are often co-localized and functionally inter-dependent. The objective of this review is to survey the evidence for interactions between the two receptor families and the mechanisms underlying them. These include the mutual regulation of subunit expression, which change the NMDA:AMPA response balance, and the existence of multi-functional receptor complexes which make it difficult to distinguish between individual receptor sites, especially in vivo. ⋯ In addition, ACh and glutamate are released as CNS co-transmitters, including 'cholinergic' synapses onto spinal Renshaw cells. It is concluded that ACh should be viewed primarily as a modulator of glutamatergic neurotransmission by regulating the release of glutamate presynaptically, and the location, subunit composition, subtype balance and sensitivity of glutamate receptors, and not primarily as a classical fast neurotransmitter. These conclusions and caveats should aid clarification of the sites of action of glutamate and nicotinic receptor ligands in the search for new centrally-acting drugs.
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Our previous work has linked childhood violence exposure in Black youth to functional changes in the hippocampus, a brain region sensitive to stress. However, different contexts of violence exposure (e.g., community, home, school) may have differential effects on circuitry. We investigated the unique effect of community violence in predicting resting-state functional connectivity (rsFC) in the hippocampus. ⋯ Age-related decreases in hippocampus-insula rsFC were also present in youth with lower violence exposure, but not in youth with higher violence exposure. This is one of the first studies to investigate the unique impact of community violence, above home and school violence, on threat circuitry. Our data suggest functional alterations in the hippocampus in violence-exposed youth, and that violence in the community may be a more salient form of threat exposure compared to other forms of violence experienced by youth.
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The ability to distinguish between threatening (repulsors), neutral and appetitive stimuli (attractors) stimuli is essential for survival. The orexinergic neurons of hypothalamus send projections to the limbic structures, such as different subregions of the medial prefrontal cortex (mPFC), suggesting that the orexinergic mechanism in the prelimbic cortex (PL) is involved in the processing of fear and anxiety. ⋯ We interpret these findings as evidence for an altered cognitive appraisal of the potential threatening stimulus. Consequently, the orexin system seems to bias the perception of stimuli towards danger or threat via OX1R and OX2R in the PL.
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Although conditioned pain modulation (CPM) is considered to represent descending pain inhibitory mechanisms triggered by noxious stimuli applied to a remote area, there have been no previous studies comparing CPM between pain and tactile systems. In this study, we compared CPM between the two systems objectively using blink reflexes. Intra-epidermal electrical stimulation (IES) and transcutaneous electrical stimulation (TS) were applied to the right skin area over the supraorbital foramen to evoke a nociceptive or a non-nociceptive blink reflex, respectively, in 15 healthy males. ⋯ Both the NRS score and nociceptive R2 were significantly decreased in the third session for IES, with a significant correlation between the two variables; whereas, TS-induced non-nociceptive R2 did not change among the sessions. Although the conditioning stimulus decreased the NRS score for TS, the CPM effect was significantly smaller than that for IES (p = 0.002). The present findings suggest the presence of a pain-specific CPM effect to a heterotopic noxious stimulus.
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Acute seizures can severely affect brain function and development. However, the underlying pathophysiological mechanisms are still poorly understood. Disturbances of the glutamatergic system are considered one of the critical mechanisms of neurological abnormalities. ⋯ Significant alterations in the expression of different receptor subunits in the mRNA but not protein levels were observed in the entorhinal cortex and amygdala. In contrast, in the medial prefrontal and temporal cortex, we found almost no changes in the expression of the studied genes. The identified changes deepen our understanding of post-seizure disturbances in the developing brain and confirm that although various brain structures are involved in seizures, the hippocampus is the most vulnerable.