No abstract

Compared with controls, IL-6 in patients was significantly elevated in plasma, saliva, and nasal mucus. Because IL-6 is a proinflammatory cytokine, these changes can relate to local or systemic inflammatory processes, which can be a cause or a result of pathological processes associated with hyposmia. These results support the concept that hyposmia has a biochemical basis and IL-6 may play a role in biochemical pathological processes underlying hyposmia and its treatment.

Although inhibition has often been proposed as a central mechanism for coordinating activity in the olfactory system, relatively little is known about how activation of different inhibitory local circuit pathways can generate coincident inhibition of principal cells. We used serotonin (5-HT) as a pharmacological tool to induce spiking in ensembles of mitral cells (MCs), a primary output neuron in the olfactory bulb, and recorded intracellularly from pairs of MCs to directly assay coincident inhibitory input. We find that 5-HT disynaptically depolarized granule cells (GCs) only slightly but robustly increased the frequency of inhibitory postsynaptic inhibitory currents in MCs. Serotonin also triggered more coincident IPSCs in pairs of nearby MCs than expected by chance, including in MCs with truncated apical dendrites that lack glomerular synapses. That serotonin-triggered coincident inhibition in the absence of elevated GC somatic firing rates suggested that synchronized MC inhibition arose from glutamate receptor-mediated depolarization of GC dendrites or other (non-GC) interneurons outside the glomerular layer. Tetanic stimulation of GCL afferents to GCs triggered robust GC spiking, coincident inhibition in pairs of MCs, and recruited large-amplitude IPSCs in MCs. Enhancing neurotransmission through NMDARs by lowering the external Mg 2+ concentration also increased inhibitory tone onto MCs but failed to promote synchronized inhibition. These results demonstrate that coincident MC inhibition can occur through multiple circuit pathways and suggests that the functional coordination between different GABAergic synapses in individual GCs can be dynamically regulated.Rhythmic sensory input to the olfactory bulb (OB), the secondorder brain region in the olfactory system, recruits complex inhibitory responses (Hamilton and Kauer 1989) that help shape spike patterns of mitral and tufted neurons during basal respiration and sniffing (Abraham et al. 2010). Divergent inhibitory input from granule cells (GCs), the most numerous interneuron subtype within the OB, onto principal cells has been proposed to mediate spike synchronization among subpopulations of principal cells (Galán et al. 2006). However, the ability of GCs, and other bulbar interneurons, to generate coincident inhibition on groups of principal neurons has been studied directly (using paired intracellular recordings) only infrequently.Coincident inhibitory responses onto mitral cells (MCs)-synaptic input that could potentially synchronize firing patterns in output neurons by either resetting intrinsic membrane potential oscillations (Desmaisons et al. 1999) Complicating the interpretation of responses to tetanic stimulation in a resonant brain region such as the OB (Rall and Shepherd 1968;Freeman 1975;Desmaisons et al. 1999;Galán et al. 2006) is the possibility that coincident spiking or synaptic activity following the stimulus might reflect the triggering stimulus rather than synchronization emerging de novo through the intrinsic properties of OB neurons or ...

To detect more alcoholic patients at risk for major complications, patients should be seen more often, and additional diagnostic tools such as the CAGE, CDT, and GGT should be used before surgery.