Sinoatrial node pacemaker cells share dominant biological properties with glutamatergic neurons

Activation of the heart normally begins in the sinoatrial node (SAN). Electrical impulses spontaneously released by SAN pacemaker cells (SANPCs) trigger the contraction of the heart. However, the cellular nature of SANPCs remains controversial. Here, we report that SANPCs exhibit glutamatergic neuron-like properties. By comparing the single-cell transcriptome of SANPCs with that of cells from primary visual cortex in mouse, we found that SANPCs co-clustered with cortical neurons. Tissue and cellular imaging confirmed that SANPCs contained key elements of glutamatergic neurotransmitter system, expressing genes encoding glutamate synthesis pathway (Gls), ionotropic and metabotropic glutamate receptors (Grina, Gria3, Grm1 and Grm5), and glutamate transporters (Slc17a7). SANPCs highly expressed cell markers of glutamatergic neurons (Snap25 and Slc17a7), whereas Gad1, a marker of GABAergic neurons, was negative. Functional studies revealed that inhibition of glutamate receptors or transporters reduced spontaneous pacing frequency of isolated SAN tissues and spontaneous Ca

Lateral Hypothalamic Area Glutamatergic Neurons and Their Projections to the Lateral Habenula Modulate the Anesthetic Potency of Isoflurane in Mice / 神经科学通报·英文版

The lateral hypothalamic area (LHA) plays a pivotal role in regulating consciousness transition, in which orexinergic neurons, GABAergic neurons, and melanin-concentrating hormone neurons are involved. Glutamatergic neurons have a large population in the LHA, but their anesthesia-related effect has not been explored. Here, we found that genetic ablation of LHA glutamatergic neurons shortened the induction time and prolonged the recovery time of isoflurane anesthesia in mice. In contrast, chemogenetic activation of LHA glutamatergic neurons increased the time to anesthesia and decreased the time to recovery. Optogenetic activation of LHA glutamatergic neurons during the maintenance of anesthesia reduced the burst suppression pattern of the electroencephalogram (EEG) and shifted EEG features to an arousal pattern. Photostimulation of LHA glutamatergic projections to the lateral habenula (LHb) also facilitated the emergence from anesthesia and the transition of anesthesia depth to a lighter level. Collectively, LHA glutamatergic neurons and their projections to the LHb regulate anesthetic potency and EEG features.

Optogenetic study of glutamatergic neuron in parasubiculum in visuospatial memory / 中华行为医学与脑科学杂志

Objective:To investigate the function of glutamatergic neuron of the parasubiculum in spatial memory.Methods:Sixteen adult male C57BL/6 mice aged 6-8 weeks were divided into two groups randomly, 0.4 μl AAV5-CaMKⅡα-eNpHR3.0-eYFP was injected into the bilateral parasubiculum respectively in experimental group, equal dose AAV5-CaMKⅡα-eYFP for control group.The optic fiber was implanted 6 weeks after virus injection.The novel object place recognition test was performed one week after optic fiber implantation, continuous yellow light was delivered during the behavioral test to inhibit the function of glutamatergic neuron in the parasubiculum.The standard memory index (D2) was used to evaluate the spatial memory function.SPSS 20.0 software was used to process the data, and the independent-samples t-test and paired-samples t-test were used for data analysis. Results:In the novel object place recognition experiment, the mice showed no preference for either object in both control group(new object: 0.51±0.06, familiar object: 0.49±0.04, t=1.21, P>0.05) and experimental group(new object: 0.49±0.05, familiar object: 0.50±0.04, t=-0.78, P>0.05). Compared with the control group (0.55±0.06), the D2 score of the experimental group (0.26±0.07) was significantly lower ( t=-2.96, P<0.05), and the number of c-fos positive neuron in experimental group (96.33±7.13) was also significantly less than that in control group (127.67±5.24, t=-3.54, P<0.05). Conclusion:Inhibiting glutamatergic neuronal activity in the parasubiculum impairs spatial memory in mice, suggesting that glutamatergic neurons of the parasubiculum play an important role in spatial memory.

Aucubin Promotes Differentiation of Neural Precursor Cells into GABAergic Neurons

Aucubin is a small compound naturally found in traditional medicinal herbs with primarily anti-inflammatory and protective effects. In the nervous system, aucubin is reported to be neuroprotective by enhancing neuronal survival and inhibiting apoptotic cell death in cultures and disease models. Our previous data, however, suggest that aucubin facilitates neurite elongation in cultured hippocampal neurons and axonal regrowth in regenerating sciatic nerves. Here, we investigated whether aucubin facilitates the differentiation of neural precursor cells (NPCs) into specific types of neurons. In NPCs cultured primarily from the rat embryonic hippocampus, aucubin significantly elevated the number of GAD65/67 immunoreactive cells and the expression of GAD65/67 proteins was upregulated dramatically by more than three-fold at relatively low concentrations of aucubin (0.01 µM to 10 µM). The expression of both NeuN and vGluT1 of NPCs, the markers for neurons and glutamatergic cells, respectively, and the number of vGluT1 immunoreactive cells also increased with higher concentrations of aucubin (1 µM and 10 µM), but the ratio of the increases was largely lower than GAD expression and GAD immunoreactive cells. The GABAergic differentiation of pax6-expressing late NPCs into GABA-producing cells was further supported in cortical NPCs primarily cultured from transgenic mouse brains, which express recombinant GFP under the control of pax6 promoter. The results suggest that aucubin can be developed as a therapeutic candidate for neurodegenerative disorders caused by the loss of inhibitory GABAergic neurons.

Advances in the study of the effect of basal forebrain on sleep-wake regulation / 药学学报

The basal forebrain (BF) is known to participate in the control of motion, attention, learning and memory, and it also plays a key role in sleep-wake regulation. Although there is a strong heterogeneity among neurons in the BF, the main types are cholinergic, gamma-aminobutyric acid (GABAergic) and glutamatergic neurons. This review provided the research progress in the regulation of sleep-wakefulness behavior by the 3 neurons in the BF. The cholinergic neurons play roles in activation of cortex and promote phase transition between sleep and wakefulness. The cortical projecting GABAergic neurons, which accept the projections from the adjacent cholinergic and glutamatergic neurons, contribute to awakening and the maintenance of normal wakefulness. The GABAergic interneurons may promote sleepiness by inhibiting the wake-active neurons which excite the cortical neurons. The glutamatergic neurons regulate sleep and wakefulness by interacting with neighbor cholinergic and cortical projecting GABAergic neurons or through the direct projection to the cortex as well.

Regulatory effects of PB on sleep and wakefulness / 中国药理学通报

The parabrachial nucleus (PB)is made up of gray matter around the Pons combination(BC),mainly consisting of glutamatergic,GABAergic and enkephalinergic neurons.PB is connected to hypothalamus and basal forebrain through a network of nerve fibers.Specific lesion of the entire parabrachial complex in animals leads to a deep coma.PB also projects to the non-rapid eye movement(NREM)-related regions including the ven-trolateral preoptic,and receives the projections from the parafa-cial zone.Activation of the GABAergic neurons in parafacial zone can promote NREM sleep,which indicates that PB partici-pates in NREM sleep.Furthermore,the lateral PB is actived when rapid eye movement(REM)sleep is deprived.In conclu-sion,PB participates in regulating wakefulness, NREM and REM sleep.This review summarizes the advances in the roles of PB in sleep-wake regulation.

The relationship of vesicular glutamate transporters and nervous system disease / 中国药理学通报

Vesicular glutamate transporters(VGLUTs)package specifically glutamate into synaptic vesicles in the presynaptic terminal for subsequent release into the synaptic cleft.VGLUT1 and VGLUT2 together label all glutamatergic neurons,are highly specific markers of glutamatergic neurons and their axon terminals.VGLUT1 and VGLUT2 are respectively the neurochemical marker of cortico-cortical projection and thalamo-cortical projection.VGLUT3 is also expressed in cholinergic interneurons,serotoninergic neurons,subsets of GABAergic interneurons in the hippocampus and cerebral cortex.The disfunction of VGLUTs can lead to the abnormal excitatory neurotransmitter glutamate,resulting in many nervous system disease.In order to give a clue for prevention and therapy of these diseases,this paper reviews the disfunction of VGLUTs effects on Alzheimer's disease(AD),Parkinson's disease(PD),schizophrenia,depressive disorder,epilepsy and deafness.