Neuroscience
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To evaluate physiological roles of the large, second cytoplasmic loops (C2) situated between the M3 and M4 transmembrane domains of nicotinic acetylcholine receptor (nAChR) subunits. We have constructed chimeric β2 (β2χ) and β4 (β4χ) subunits in which the "nested" C2 domains (but not the "proximal" sequences of ∼14 residues immediately adjacent to the M3 or M4 domains) of these β subunits were replaced by the corresponding sequence from the serotonin 5-HT3A receptor subunit. We previously reported that heterologously expressed nAChR containing α4 and β2χ subunits displayed a faster whole-cell current decay in its agonist response compared to responses of all-wild-type α4β2-nAChR. ⋯ In addition, cell-attached, single-channel recording shows that both acetylcholine-activated α4β2χ- and α4β4χ-nAChR have a significantly lower mean open probability, shorter mean open-time, and a longer mean closed-time than their fully wild-type counterparts while not having different conductance amplitudes. These findings reveal microscopic bases for the faster desensitization of α4(∗)-nAChR containing chimeric instead of wild-type β subunits. Our findings also remain consistent with novel and unexpected roles of β subunit-nested C2 domains in modulation of α4(∗)-nAChR function.
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The corticotropin-releasing factor (CRF)-producing neurons of the amygdala have been implicated in behavioral and physiological responses associated with fear, anxiety, stress, food intake and reward. To overcome the difficulties in identifying CRF neurons within the amygdala, a novel transgenic mouse line, in which the humanized recombinant Renilla reniformis green fluorescent protein (hrGFP) is under the control of the CRF promoter (CRF-hrGFP mice), was developed. First, the CRF-hrGFP mouse model was validated and the localization of CRF neurons within the amygdala was systematically mapped. ⋯ C-Fos induction was observed in CRF neurons of CRF-hrGFP mice exposed to an acute social defeat stress event, a fasting/refeeding paradigm or lipopolysaccharide (LPS) administration. In contrast, no c-Fos induction was detected in CRF neurons of CRF-hrGFP mice exposed to restraint stress, forced swimming test, 48-h fasting, acute high-fat diet (HFD) consumption, intermittent HFD consumption, ad libitum HFD consumption, HFD withdrawal, conditioned HFD aversion, ghrelin administration or melanocortin 4 receptor agonist administration. Thus, this study fully characterizes the distribution of amygdala CRF neurons in mice and suggests that they are involved in some, but not all, stress or food intake-related behaviors recruiting the amygdala.
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Although the neural correlates that underlie abdominal pain have been investigated, so-called brain processes involved in modulating "gut feelings" remain unclear. In the current study, we used electrointestinography (EIG) to measure intestinal activity of healthy humans at rest. EIG measured myoelectrical activity of intestinal smooth muscles from the abdominal surface and was simultaneously conducted along with brain activity measurement using functional magnetic resonance imaging (fMRI). ⋯ Neural activity correlating with 0.14- to 0.21-Hz EIG (suggested to reflect intestinal activity) was observed in the right anterior and middle insula. Moreover, this EIG frequency band correlated with anxiety scores along with resting-state functional connectivity between the insula and dorsal anterior cingulate cortex. These findings suggest that the insular cortex could be the core region involved in central visceral processes associated with subjective feelings.
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Recent studies of electromagnetic ultra-slow waves (⩽0.1Hz) have suggested that they play a role in the integration of otherwise disassociated brain regions supporting vital functions (Ackermann and Borbely, 1997; Picchioni et al., 2010; Knyazev, 2012; Le Bon et al., 2012). We emphasize this spectral domain in probing sensor coherence issues raised by these studies using Hilbert phase coherences in the human MEG. In addition, we ask: will temporal-spatial phase coherence in regional brain oscillations obtained from the ultraslow spectral bands of multi-channel magnetoencephalograms (MEG) differentiate resting, "task-free" MEG records of normal control and schizophrenic subjects? The goal of the study is a comparison of the relative persistence of intra-regional phase locking values (PLVs), among 10, region-defined, sensors in examined in the resting multichannel, MEG records as a function of spectral frequency bands and diagnostic category. ⋯ Leave one out, bootstrapping of the PLVs via a support vector machine (SVM), classified clinical status with 97.3% accuracy. It was generally the case that spectral bands ⩽1.0Hz generated the highest values of the PLVs and discriminated best between control and patient populations. We conclude that PLV analysis of the oscillatory patterns of MEG recordings in the ultraslow frequency bands suggest their functional significance in intra-regional signal coherence and provide a higher rate of classification of patients and normal subjects than the other spectral domains examined.
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Melanin-concentrating hormone [MCH] is a neuropeptide that modulates several behaviors, such as feeding and reward. Because the hedonic and rewarding features of a food also influence feeding behavior, the nucleus accumbens [Acb] has been highlighted as a key area integrating these roles. Functional data confirm that MCH acts on a subdivision of the Acb; however, considering the importance of finding anatomical and neurochemical data that correlate the previously demonstrated function of MCH, we delineated this investigation based on the following points: (1) Is there a pattern of innervation by MCH fibers regarding the subregions within the Acb? (2) Specifically, which hypothalamic nuclei synthesize MCH and innervate the Acb? (3) Finally, what are the neurochemical identities of the accumbal neurons innervated by MCH inputs? We examined the MCH immunoreactivity [MCH-ir] in the Acb in rat brains using the peroxidase technique. ⋯ Moreover, the IHy has the highest relationship between double/single retrogradely labeled cells [n=5.33±0.66/16±0.93, i.e. 33.33%] in the whole hypothalamus. Furthermore, our data suggest that MCH-ir fibers are in apposition to GABAergic and cholinergic cells in the AcbSh. Therefore, we provide anatomical support to the ongoing functional studies investigating the relation among the hypothalamus, MCH transmission into the Acb and the involvement of known neuronal phenotypes within the AcbSh.