The Journal of neuroscience : the official journal of the Society for Neuroscience
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The molecular mechanisms underlying stress- and drug-induced neuronal adaptations are incompletely understood. One molecule implicated in such adaptations is ΔFosB, a transcription factor that accumulates in the rodent nucleus accumbens (NAc), a key brain reward region, in response to either chronic stress or repeated exposure to drugs of abuse. The upstream transcriptional mechanisms controlling ΔFosB induction by these environmental stimuli remain elusive. ⋯ Furthermore, NAc-specific genetic deletion of SRF promotes a variety of prodepressant- and proanxiety-like phenotypes and renders animals more sensitive to the deleterious effects of chronic stress. In contrast, we demonstrate that SRF does not play a role in ΔFosB accumulation in NAc in response to chronic cocaine exposure. Furthermore, NAc-specific knock-out of SRF has no effect on cocaine-induced behaviors, indicating that chronic social defeat stress and repeated cocaine exposure regulate ΔFosB accumulation and behavioral sensitivity through independent mechanisms.
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Alterations in cortical excitability are implicated in the pathophysiology of migraine. However, the relationship between cortical spreading depression (CSD) and headache has not been fully elucidated. We aimed to identify the corticofugal networks that directly influence meningeal nociception in the brainstem trigeminocervical complex (Sp5C) of the rat. ⋯ CSD triggered in V1 affects differently Ins and S1 cortices, enhancing or inhibiting meningeal-evoked responses of Sp5C, without affecting cutaneous-evoked nociceptive responses. Our data suggest that "top-down" influences from lateralized areas within Ins and S1 selectively affect interoceptive (meningeal) over exteroceptive (cutaneous) nociceptive inputs onto Sp5C. Such corticofugal influences could contribute to the development of migraine pain in terms of both topographic localization and pain tuning during an attack.
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The role of GABA(B) receptors in sleep is still poorly understood. GHB (γ-hydroxybutyric acid) targets these receptors and is the only drug approved to treat the sleep disorder narcolepsy. GABA(B) receptors are obligate dimers comprised of the GABA(B2) subunit and either one of the two GABA(B1) subunit isoforms, GABA(B1a) and GABA(B1b). ⋯ Subsequent sleep was not affected by GBL whereas BAC was followed by a delayed hypersomnia even in 1(-/-) and 2(-/-) mice. The differential effects of GBL and BAC might be attributed to differences in GABA(B)-receptor affinity. These results also indicate that all GBL effects are mediated through GABA(B) receptors, although these receptors do not seem to be involved in mediating the BAC-induced hypersomnia.
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GABA transmission in the ventral tegmental area (VTA) is critical for fine tuning the activity of dopamine neurons in response to opioids. However, the precise mechanism by which GABA input shapes opioid reward is poorly understood. ⋯ Importantly, pretreatment with the cAMP signaling inhibitor (R)-adenosine, cyclic 3',5'-(hydrogenphosphorothioate) triethylammonium both restored DAMGO reward and reversed the DAMGO-mediated potentiation, thereby reestablishing the inhibitory effects of opioids on GABA currents. Thus, a paradoxical bidirectionality in μ-receptor-mediated control of GABA transmission following chronic morphine treatment is a critical mechanism that determines the expression of opioid reward in the VTA.
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Comparative Study
Comparisons of the dynamics of local field potential and multiunit activity signals in macaque visual cortex.
The local field potential (LFP) and multiunit activity (MUA) are extracellularly recorded signals that describe local neuronal network dynamics. In our experiments, the LFP and MUA, recorded from the same electrode in macaque primary visual cortex V1 in response to drifting grating visual stimuli, were evaluated on coarse timescales (∼1-5 s) and fine timescales (<0.1 s). On coarse timescales, MUA and the LFP both produced sustained visual responses to optimal and non-optimal oriented visual stimuli. ⋯ The LFP and MUA were weakly but significantly coherent (∼0.14) in the gamma band (20-90 Hz). The amount of gamma-band coherence was correlated with the power in the gamma band of the LFP. The data were consistent with the proposal that the LFP and MUA are generated in a noisy, resonant cortical network.