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Abstract It is well established that the medial prefrontal cortex (mPFC) exerts top-down control of many behaviors, but little is known regarding how cross-talk between distinct areas of the mPFC influences top-down signaling. We performed virus-mediated tracing and functional studies in male mice, homing in on GABAergic projections whose axons are located mainly in layer 1 and that connect two areas of the mPFC, namely the prelimbic area (PrL) with the cingulate area 1 and 2 (Cg1/2). We revealed the identity of the targeted neurons that comprise two distinct types of layer 1 GABAergic interneurons, namely single-bouquet cells (SBCs) and neurogliaform cells (NGFs), and propose that this connectivity links GABAergic projection neurons with cortical canonical circuits. In vitro electrophysiological and in vivo calcium imaging studies support the notion that the GABAergic projection neurons from the PrL to the Cg1/2 exert a crucial role in regulating the activity in the target area by disinhibiting layer 5 output neurons. Finally, we demonstrated that recruitment of these projections affects impulsivity and mechanical responsiveness, behaviors which are known to be modulated by Cg1/2 activity.

Abstract Dianthi herba (called “Qumai” in Chinese) is the dried aerial part of Dianthus superbus L. and Dianthus chinensis L. The species are mainly distributed in the temperate and warm temperate regions in the northern hemisphere, and some regions in Africa and Oceania, as well as South America. However, the distribution pattern of Dianthi herba has not been reviewed. In this review, we summarize the research progress on the botany, traditional use, phytochemistry, pharmacology, toxicology, and clinical applications of Dianthi herba. Approximately 194 chemical compounds have been identified and isolated from Dianthi herba, the most important being triterpenoid saponins, flavonoids, and volatile oil compounds. These compounds possess antiviral, anticancer, antioxidant, and antimicrobial properties, inter alia. Further studies should be carried out on Dianthi herba to elucidate more of its active principles and their mechanisms of action.

Lamotrigine (LTG) is generally considered as a voltage-gated sodium (Nav) channel blocker. However, recent studies suggest that LTG can also serve as a hyperpolarization-activated cyclic nucleotide-gated (HCN) channel enhancer and can increase the excitability of GABAergic interneurons (INs). Perisomatic inhibitory INs, predominantly fast-spiking basket cells (BCs), powerfully inhibit granule cells (GCs) in the hippocampal dentate gyrus. Notably, BCs express abundant Nav channels and HCN channels, both of which are able to support sustained action potential generation. Using whole-cell recording in rat hippocampal slices, we investigated the net LTG effect on BC output. We showed that bath application of LTG significantly decreased the amplitude of evoked compound inhibitory postsynaptic currents (IPSCs) in GCs. In contrast, simultaneous paired recordings from BCs to GCs showed that LTG had no effect on both the amplitude and the paired-pulse ratio of the unitary IPSCs, suggesting that LTG did not affect GABA release, though it suppressed cell excitability. In line with this, LTG decreased spontaneous IPSC (sIPSC) frequency, but not miniature IPSC frequency. When re-examining the LTG effect on GABAergic transmission in the cornus ammonis region 1 (CA1) area, we found that LTG markedly inhibits both the excitability of dendrite-targeting INs in the stratum oriens and the concurrent sIPSCs recorded on their targeting pyramidal cells (PCs) without significant hyperpolarization-activated current (Ih) enhancement. In summary, LTG has no effect on augmenting Ih in GABAergic INs and does not promote GABAergic inhibitory output. The antiepileptic effect of LTG is likely through Nav channel inhibition and the suppression of global neuronal network activity.

NG2 cells, a fourth type of glial cell in the mammalian CNS, undergo reactive changes in response to a wide variety of brain insults. Recent studies have demonstrated that neuronally expressed acid-sensing ion channels (ASICs) are implicated in various neurological disorders including brain ischemia and seizures. Acidosis is a common feature of acute neurological conditions. It is postulated that a drop in pH may be the link between the pathological process and activation of NG2 cells. Such postulate immediately prompts the following questions: Do NG2 cells express ASICs? If so, what are their functional properties and subunit composition? Here, using a combination of electrophysiology, Ca2+ imaging and immunocytochemistry, we present evidence to demonstrate that NG2 cells of the rat hippocampus express high density of Ca2+-permeable ASIC1a channels compared with several types of hippocampal neurons. First, nucleated patch recordings from NG2 cells revealed high density of proton-activated currents. The magnitude of proton-activated current was pH dependent, with a pH for half-maximal activation of 6.3. Second, the current-voltage relationship showed a reversal close to the equilibrium potential for Na+. Third, psalmotoxin 1, a blocker specific for the ASIC1a channel, largely inhibited proton-activated currents. Fourth, Ca2+ imaging showed that activation of proton-activated channels led to an increase of [Ca2+]i. Finally, immunocytochemistry showed co-localization of ASIC1a and NG2 proteins in the hippocampus. Thus the acid chemosensor, the ASIC1a channel, may serve for inducing membrane depolarization and Ca2+ influx, thereby playing a crucial role in the NG2 cell response to injury following ischemia.

The dentate gyrus (DG) serves as a primary gate to control information transfer from the cortex to the hippocampus. Activation of incoming cortical inputs results in rapid synaptic excitation followed by slow GABA-mediated (GABAergic) synaptic inhibition onto DG granule cells (GCs). GABAergic inhibitory interneurons (INs) in the DG comprise fast-spiking (FS) and non-fast-spiking (non-FS) cells. Anatomical analyses of DG INs reveal that FS cells are soma-targeting INs, whereas non-FS cells are dendrite-targeting INs. These two IN classes are differentially recruited by excitatory inputs and in turn provide exquisite spatiotemporal control over GC activity. Yet, little is known how FS and non-FS cells transform their presynaptic dynamics into varying postsynaptic response amplitudes. Using paired recordings in rat hippocampal slices, we show that inhibition in the DG is dominated by somatic GABAergic inputs during periods of sparse presynaptic activity, whereas dendritic GABAergic inputs are rapidly shifted to powerful and sustained inhibition during periods of intense presynaptic activity. The variant dynamics of dendritic inhibition is dependent on presynaptic IN subtypes and their activity patterns and is attributed to Ca2+-dependent increases in the probability of release and the size of the readily releasable pool. Furthermore, the degree of dynamic GABA release can be reduced by blocking voltage-gated K+ channels, which increases the efficacy of dendrite-targeting IN output synapses during sparse firing. Such rapid dynamic modulation of dendritic inhibition may act as a frequency-dependent filter to prevent overexcitation of GC dendrites and thus set the excitatory-inhibitory synaptic balance in the DG circuits. [ABSTRACT FROM AUTHOR]

Background. To investigate the specific link between lung and large intestine. Methods. Rat COPD-like model was prepared. Mirabilite or Chinese rhubarb was administrated intragastrically to stimulate the large intestine. Histological analysis of lung inflammation was assessed. The tissues levels of SP, VIP, NK1R, VIPR1, and VIPR2 were measured by using ELISA kits. In addition, mouse model of allergic asthma was prepared. Mirabilite was administrated intragastrically to stimulate the large intestine. Airway responsiveness and lung inflammation were assessed. The tissues levels of SP, VIP, NKA, NKB, NK1R, VIPR1, and VIPR2 were measured by using ELISA kits. Results. Stimulating the intestine with Mangxiao or Dahuang, SP, NK-1R, VIP, VIPR1, and VIPR2 were significantly increased in intestine tissues of rats with COPD and mice with asthma. Meanwhile, the SP and NK1R were significantly decreased, while VIP, VIPR1, and VIPR2 were significantly increased in lung tissues. An abnormal secretion of SP and VIP can be observed in other tissues; however, no marked changes were found in the receptors. The NKA and NKB levels were similar in lung tissues of mice with asthma among groups. Conclusions. Stimulating intestine with Mangxiao or Dahuang can specifically regulate the secretion of SP, VIP, and the receptors in lung tissues. [ABSTRACT FROM AUTHOR]

GABAergic signaling in hippocampal pyramidal neurons undergoes a switch from depolarizing to hyperpolarizing during early neuronal development. Whether such a transformation of GABAergic action occurs in dentate granule cells (DGCs), located at the first stage of the hippocampal trisynaptic circuit, is unclear. Here, we use noninvasive extracellular recording to monitor the effect of synaptically released GABA on the DGC population. We find that GABAergic responses in adolescent and adult rat DGCs are still depolarizing from rest. Using a morphologically realistic DGC model, we show that GABAergic action, depending on its precise timing and location, can have either an excitatory or inhibitory role in signal processing in the dentate gyrus. [ABSTRACT FROM AUTHOR]

NG2 cells, a fourth type of glial cell in the mammalian CNS, undergo reactive changes in response to a wide variety of brain insults. Recent studies have demonstrated that neuronally expressed acid-sensing ion channels (ASICs) are implicated in various neurological disorders including brain ischemia and seizures. Acidosis is a common feature of acute neurological conditions. It is postulated that a drop in pH may be the link between the pathological process and activation of NG2 cells. Such postulate immediately prompts the following questions: Do NG2 cells express ASICs? If so, what are their functional properties and subunit composition? Here, using a combination of electrophysiology, Ca2+ imaging and immunocytochemistry, we present evidence to demonstrate that NG2 cells of the rat hippocampus express high density of Ca2+- permeable ASIC1a channels compared with several types of hippocampal neurons. First, nucleated patch recordings from NG2 cells revealed high density of proton-activated currents. The magnitude of proton-activated current was pH dependent, with a pH for half-maximal activation of 6.3. Second, the current-voltage relationship showed a reversal close to the equilibrium potential for Na+. Third, psalmotoxin 1, a blocker specific for the ASIC1a channel, largely inhibited proton-activated currents. Fourth, Ca2+ imaging showed that activation of proton-activated channels led to an increase of [Ca2+]i. Finally, immunocytochemistry showed co-localization of ASIC1a and NG2 proteins in the hippocampus. Thus the acid chemosensor, the ASIC1a channel, may serve for inducing membrane depolarization and Ca2+ influx, thereby playing a crucial role in the NG2 cell response to injury following ischemia. [ABSTRACT FROM AUTHOR]