Brain research
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Patients with neuropathic pain present not only with persistent pain but also a complex set of additional symptoms, including mood disorders and cognitive disturbance. Given the important roles of the anterior thalamic nuclei (ATN) and anterior cingulate cortex (ACC) in the cognitive and emotional aspects of pain, investigation of the properties of ATN-ACC synapses will help us to understand the mechanisms underlying neuropathic pain. ⋯ A possible explanation for the neuropathic pain-related suppression of EPSPs is that the ACC was already sufficiently active at baseline as a result of neuropathic pain, and ATN stimulation could not further increase the already elevated level of ACC activity. This abnormal excitability of the ATN-ACC synapse may be important in understanding the mechanism underlying neuropathic pain, particularly with respect to the affective and cognitive aspects.
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Microglia activated after brain injury, are a major source of the pro-inflammatory cytokine interleukin-1 (IL-1), which is known to further exacerbate damage. However, the mechanisms that control IL-1 release in acute neuronal injury are unknown and the purpose of this study was to test the hypothesis that neuronal injury induces IL-1beta release from microglial cells. Here we report that lipopolysaccharide (LPS)-activated rat microglia co-cultured with healthy rat neurons express pro-IL-1beta, which in the absence of cell death accumulates in the cells. ⋯ This effect was reversed by the NMDA receptor antagonist MK-801, and was neuron-dependent, since NMDA had no effect on cell death or pro-IL-1beta release in mixed glial cell cultures. In addition, we show that pro-IL-1beta release from LPS-treated mixed glia or LPS-treated microglia is significantly reduced in the presence of conditioned medium from healthy co-cultures or neuronal cultures respectively. These results demonstrate that injured neurons promote the release of pro-IL-1beta from microglia, possibly by regulating microglial cell viability, and suggest an important alternative mechanism of IL-1beta release that occurs in response to neuronal injury.
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The analysis of the functional correlates of "brain oscillations" has become an important branch of neuroscience. Although research on the functional correlates of brain oscillation has progressed to a high level, studies on cognitive disorders are rare and mainly limited to schizophrenia patients. ⋯ Furthermore, the effects of pharmaca and the influence of neurotransmitters in patients with cognitive disorders are also reviewed. Following the review, a short synopsis is given related to the analysis of brain oscillations.
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The brain generates extensive spontaneous network activity patterns, even in the absence of extrinsic afferents. While the cognitive correlates of these complex activities are being unraveled, the rules that govern the generation, synchronization and spread of different patterns of intrinsic network activity in the brain are still enigmatic. Using hippocampal neurons grown in dissociated cultures, we are able to study these rules. ⋯ Thus, the strength of connectivity is inversely correlated with spontaneous activity and synchronicity. In the absence of confirmed 'leader' neurons, synchronous bursting network activity appears to be triggered by at least several local subthreshold synaptic events. We conclude that networks of neurons in culture can produce spontaneous synchronized activity and serve as a viable model system for the analysis of the rules that govern network activity in the brain.
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Pyrithiamine-induced thiamine deficiency (PTD) was used to produce a rodent model of Wernicke-Korsakoff syndrome that results in acute neurological disturbances, thalamic lesions, and learning and memory impairments. There is also cholinergic septohippocampal dysfunction in the PTD model. Systemic (Experiment 1) and intrahippocampal (Experiment 2) injections of the acetylcholinesterase inhibitor physostigmine were administered to determine if increasing acetylcholine levels would eliminate the behavioral impairment produced by PTD. ⋯ In addition, although intrahippocampal infusions of 40 ng of physostigmine increased the available amount of ACh in both pair-fed (PF) and PTD rats, it did so to a greater extent in PF rats. The increase in ACh levels induced by the direct hippocampal application of physostigmine in the PTD model likely increased activation of the extended limbic system, which was dysfunctional, and therefore led to recovery of function on the spontaneous alternation task. In contrast, the lack of behavioral improvement by intrahippocampal physostigmine infusion in the PF rats, despite a greater rise in hippocampal ACh levels, supports the theory that there is an optimal range of cholinergic tone for optimal behavioral and hippocampal function.