Neuroscience
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The modulatory neurotransmitter dopamine induces concentration-dependent changes in synaptic transmission in the entorhinal cortex, in which high concentrations of dopamine suppress evoked excitatory postsynaptic potentials (EPSPs) and lower concentrations induce an acute synaptic facilitation. Whole-cell current-clamp recordings were used to investigate the dopaminergic facilitation of synaptic responses in layer II neurons of the rat lateral entorhinal cortex. A constant bath application of 1 μM dopamine resulted in a consistent facilitation of EPSPs evoked in layer II fan cells by layer I stimulation; the size of the facilitation was more variable in pyramidal neurons, and synaptic responses in a small group of multiform neurons were not modulated by dopamine. ⋯ Dopamine D₁ receptors lead to activation of protein kinase A (PKA), and including the PKA inhibitor H-89 or KT 5720 in the recording pipette solution prevented the facilitation of EPSCs. PKA-dependent phosphorylation of inhibitor 1 or the dopamine- and cAMP-regulated protein phosphatase (DARPP-32) can lead to a facilitation of AMPA receptor responses by inhibiting the activity of protein phosphatase 1 (PP1) that reduces dephosphorylation of AMPA receptors, and we found here that inhibition of PP1 occluded the facilitatory effect of dopamine. The dopamine-induced facilitation of AMPA receptor-mediated synaptic responses in layer II neurons of the lateral entorhinal cortex is therefore likely mediated via a D₁ receptor-dependent increase in PKA activity and a resulting inhibition in PP1-dependent dephosphorylation of AMPA receptors.
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The cochlear nucleus (CN) and superior olivary complex are auditory brainstem centers with essential roles in encoding temporal features of vocalizations, localization of sound sources and descending modulation of the cochlea. Numerous neuronal populations, across a multitude of laboratory mammals, have been characterized within these brainstem centers based on cell body morphology, dendritic architecture, afferent/efferent connections and neurochemistry. However, scant details are available for these neuronal populations in humans. ⋯ To this end, we have used immunohistochemistry and morphometric techniques to characterize neuronal populations and axonal projections in the human brainstem. Herein, we provide evidence for calretinin immunoreactive neurons and synaptic boutons in the ventral CN, axons in the trapezoid body, peridendritic boutons in the medial superior olive and calyceal endings in the medial nucleus of the trapezoid body (MNTB). Further, we demonstrate that the majority of neurons in the human MNTB are calbindin and Kv3.1b immunoreactive and that perisomatic profiles in this nucleus are vesicular glutamate transporter and Rab3a positive, suggesting that such profiles are in fact synaptic terminals.
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A fundamental role of the taste system is to discriminate between nutritive and toxic foods. However, it is unknown whether bacterial pathogens that might contaminate food and water modulate the transmission of taste input to the brain. We hypothesized that exogenous, bacterially-derived lipopolysaccharide (LPS), modulates neural responses to taste stimuli. ⋯ These findings demonstrate that ingestion of LPS during a single period specifically and transiently inhibits neural responses to sucrose. We suggest that LPS drinking initiates TLR4-dependent hormonal signals that downregulate sweet taste receptor genes in taste buds. Delayed inhibition of sweet taste signaling may influence food selection and the complex interplay between gastrointestinal bacteria and obesity.
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Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is a tumor suppressor gene that regulates various cell processes including proliferation, growth, synaptogenesis, neural and glioma stem/progenitor cell renewal. In addition, PTEN can regulate sensory cell proliferation and differentiation of hair bundles in the mammalian cochlea. In this study we use immunofluorescence, Western blot and reverse transcriptase-polymerase chain reaction (RT-PCR) to reveal the expression of PTEN in the developing cochlear lateral wall, which is crucial for regulating K(+) homeostasis. ⋯ Similarly high levels are subsequently expressed in differentiating root cells (RCs) at postnatal day (P) 3 and then in spiral ligament fibrocytes (SLFs) at P 10. In the mature cochlea, PTEN expression is low or undetectable in MCs and SLFs but it remains high in RCs and their processes. The expression pattern for PTEN in the developing lateral wall suggests that it plays a critical role in the differentiation of the cellular pathways that regulate K(+) homeostasis in the cochlea.
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Although the clearance of glutamate from the synapse under physiological conditions is performed by astrocytic glutamate transporters, their expression might be diminished under pathological conditions. Microglia glutamate transporters, however, might serve as a back-up system when astrocytic glutamate uptake is impaired, and could have a prominent neuroprotective function under pathological conditions. In the current study, the effect of nicotine, well known as a neuroprotective molecule, on the function of glutamate transporters in cultured rat cortical microglia was examined. ⋯ Treatment of cortical microglia with nicotine led to a significant increase of GLAST mRNA expression and (14)C-glutamate uptake in a concentration- and time-dependent manner, which were markedly inhibited by pretreatment with methyllycaconitine, a selective α7 nACh receptor antagonist. The nicotine-induced expression of GLAST mRNA and protein is mediated through an inositol trisphosphate (IP3) and Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) depend intracellular pathway, since pretreatment with either xestospongin C, an IP3 receptor antagonist, or KN-93, a CaMKII inhibitor, blocked GLAST expression. Together, these findings indicate that activation of nACh receptors, specifically those expressing the α7 subunit, on cortical microglia could be a key mechanism of the neuroprotective effect of nACh receptor ligands such as nicotine.