135 research outputs found

    Allosteric L5-Directed Inhibitors of Kinesin-5 Can Control Different Biochemical Intermediates

    Get PDF

    Numerical assessment of the reduction of specific absorption rate by adding high dielectric materials for fetus MRI at 3 T

    Get PDF
    The specific absorption rate (SAR) is an important issue to be considered in fetus MRI at 3 T due to the high radiofrequency energy deposited inside the body of pregnant woman. The high dielectric material (HDM) has shown its potential for enhancing B field and reducing SAR in MRI. The aim of this study is to assess the feasibility of SAR reduction by adding an HDM to the fetus MRI. The feasibility of SAR reduction is numerically assessed in this study, using a birdcage coil in transmission loaded with an electromagnetic pregnant woman model in the SEMCAD-EM solver. The HDMs with different geometric arrangements and dielectric constants are manually optimized. The B1+ B−1+{B-1}^ + homogeneity is also considered while calculating the optimized fetus 10 g local SAR among different strategies in the application of HDM. The optimum maximum fetus 10 g local SAR was obtained as 2.25 W/kg, by using two conformal pads placed left and right with the dielectric constant to be 400, reduced by 24.75% compared to that without the HDM. It indicated that the SAR can be significantly reduced with strategic placement of the HDM and the use of HDM may provide a simple, effective and low-cost method for reducing the SAR for the fetus MRI at 3 T

    Behavioral/Cognitive Acute and Long-Term Suppression of Feeding Behavior by POMC Neurons in the Brainstem and Hypothalamus, Respectively

    Get PDF
    POMC-derived melanocortins inhibit food intake. In the adult rodent brain, POMC-expressing neurons are located in the arcuate nucleus (ARC) and the nucleus tractus solitarius (NTS), but it remains unclear how POMC neurons in these two brain nuclei regulate feeding behavior and metabolism differentially. Using pharmacogenetic methods to activate or deplete neuron groups in separate brain areas, in the present study, we show that POMC neurons in the ARC and NTS suppress feeding behavior at different time scales. Neurons were activated using the DREADD (designer receptors exclusively activated by designer drugs) method. The evolved human M3-muscarinic receptor was expressed in a selective population of POMC neurons by stereotaxic infusion of Cre-recombinase–dependent, adenoassociated virus vectors into the ARC or NTS of POMC-Cre mice. After injection of the human M3-muscarinic receptor ligand clozapine-N-oxide (1 mg/kg, i.p.), acute activation of NTS POMC neurons produced an immediate inhibition of feeding behavior. In contrast, chronic stimulation was required for ARC POMC neurons to suppress food intake. Using adeno-associated virus delivery of the diphtheria toxin receptor gene, we found that diphtheria toxin–induced ablation of POMC neurons in the ARC but not the NTS, increased food intake, reduced energy expenditure, and ultimately resulted in obesity and metabolic and endocrine disorders. Our results reveal different behavioral functions of POMC neurons in the ARC and NTS, suggesting that POMC neurons regulate feeding and energy homeostasis by integrating long-term adiposity signals from the hypothalamus and short-term satiety signals from the brainstem

    Npas1+ Pallidal Neurons Target Striatal Projection Neurons

    Get PDF
    Compelling evidence demonstrates the external globus pallidus (GPe) plays a key role in processing sensorimotor information. An anatomical projection from the GPe to the dorsal striatum (dStr) has been described for decades. However, the cellular target and functional impact of this projection remain unknown. Using cell-specific transgenic mice, modern monosynaptic tracing techniques, and optogenetics-based mapping, we discovered that GPe neurons provide inhibitory inputs to direct- and indirect-pathway striatal projection neurons (SPNs). Our results indicate that the GPe input to SPNs arises primarily from Npas1- expressing neurons and is strengthened in a chronic Parkinson’s disease (PD) model. Alterations of the GPe-SPN input in a PD model argue for the critical position of this connection in regulating basal ganglia motor output, arguing that strengthening of GPe-SPN connection is maladaptive and may underlie the hypokinetic symptoms in PD

    Functional connectivity of the anterior forebrain pathway in the song system

    No full text
    The avian song system is the neural substrate underlying song learning and production. The anterior forebrain pathway (AFP) in the song system is regarded as a learning pathway, since lesions of this pathway in juveniles result in abnormal song development but lesions in adults do not disrupt songs. It consists of a loop serially connecting area X in the basal ganglia, the medial portion of the dorsolateral nucleus of the anterior thalamus (DLM) and the lateral portion of the magnocellular nucleus in the pallial area (lMAN). We want to test whether the AFP has neural mechanisms similar to those of the mammalian basal ganglia-thalamocortical pathway. Specifically, we want to examine in male zebra finches (1) whether the entire AFP is organized topographically and forms parallel, closed microscopic loops, (2) whether the area X → DLM projection is GABAergic, and (3) whether the DLM neurons have intrinsic properties similar to those of the mammalian thalamocortical neurons. By making small tracer injections into area X or lMAN, we found that the area X → DLM projection was topographic and confirmed the topography for other projections within the AFP. Quantification of the spatial mapping of all projections as well as dual-tram injections into corresponding areas in lMAN and area X strongly suggest that the AFP contains many closed, parallel loops. By combining immunostaining for glutamic acid decarboxylase with tract tracing or ibotenic acid lesion, we found that DLM receives a strong and the only GABAergic input from area X. In brain slices, we recorded juvenile or adult DLM neurons with whole-cell recording techniques. Stimulating afferent axons evoked strong monosynaptic; IPSPs that were completely blocked by the GABAA receptor blocker bicuculline methiodide. Most DLM neurons had intrinsic properties almost identical to those of mammalian thalamocortical neurons and these properties were largely maintained during the sensorimotor learning phase and in the adulthood. In summary, our studies show that the AFP is organized highly similarly to the mammalian basal ganglia-thalamocortical pathway at both macroscopic and cellular levels, suggesting that the AFP functions in song learning similarly to the mammalian basal ganglia pathway in sensorimotor learning

    Functional connectivity of the anterior forebrain pathway in the song system

    No full text
    The avian song system is the neural substrate underlying song learning and production. The anterior forebrain pathway (AFP) in the song system is regarded as a learning pathway, since lesions of this pathway in juveniles result in abnormal song development but lesions in adults do not disrupt songs. It consists of a loop serially connecting area X in the basal ganglia, the medial portion of the dorsolateral nucleus of the anterior thalamus (DLM) and the lateral portion of the magnocellular nucleus in the pallial area (lMAN). We want to test whether the AFP has neural mechanisms similar to those of the mammalian basal ganglia-thalamocortical pathway. Specifically, we want to examine in male zebra finches (1) whether the entire AFP is organized topographically and forms parallel, closed microscopic loops, (2) whether the area X → DLM projection is GABAergic, and (3) whether the DLM neurons have intrinsic properties similar to those of the mammalian thalamocortical neurons. By making small tracer injections into area X or lMAN, we found that the area X → DLM projection was topographic and confirmed the topography for other projections within the AFP. Quantification of the spatial mapping of all projections as well as dual-tram injections into corresponding areas in lMAN and area X strongly suggest that the AFP contains many closed, parallel loops. By combining immunostaining for glutamic acid decarboxylase with tract tracing or ibotenic acid lesion, we found that DLM receives a strong and the only GABAergic input from area X. In brain slices, we recorded juvenile or adult DLM neurons with whole-cell recording techniques. Stimulating afferent axons evoked strong monosynaptic; IPSPs that were completely blocked by the GABAA receptor blocker bicuculline methiodide. Most DLM neurons had intrinsic properties almost identical to those of mammalian thalamocortical neurons and these properties were largely maintained during the sensorimotor learning phase and in the adulthood. In summary, our studies show that the AFP is organized highly similarly to the mammalian basal ganglia-thalamocortical pathway at both macroscopic and cellular levels, suggesting that the AFP functions in song learning similarly to the mammalian basal ganglia pathway in sensorimotor learning

    Loss of CO2 sensing by the olfactory system of CNGA3 knockout mice

    No full text
    Atmospheric CO2 can signal the presence of food, predators or environmental stress and trigger stereotypical behaviors in both vertebrates and invertebrates. Recent studies have shown that the necklace olfactory system in mice sensitively detects CO2 in the air. Olfactory CO2 neurons are believed to rely on cyclic guanosine monophosphate (cGMP) as the key second messenger; however, the specific ion channel underlying CO­2 responses remains unclear. Here we show that CO2-evoked neuronal and behavioral responses require cyclic nucleotide-gated (CNG) channels consisting of the CNGA3 subunit. Through Ca2+-imaging, we found that CO2-triggered Ca2+ influx was abolished in necklace olfactory sensory neurons (OSNs) of CNGA3-knockout mice. Olfactory detection tests using a Go/No-go paradigm showed that these knockout mice failed to detect 0.5% CO2. Thus, sensitive detection of atmospheric CO2 depends on the function of CNG channels consisting of the CNGA3 subunit in necklace OSNs. These data support the important role of the necklace olfactory system in CO2 sensing and extend our understanding of the signal transduction pathway mediating CO2 detection in mammals [Current Zoology 56 (6): 793–799, 2010]
    • …
    corecore