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Hodgkin–Huxley (HH) circuit can reproduce abundant neuronal firing activities, but it is hard to physically implement the HH circuit. To solve this issue, an implementable HH circuit with two N-type locally active memristors (LAMs) to respectively characterize its Na + and K + channels is proposed in this paper. Numerical explorations demonstrate that the N-type LAM-based Hodgkin–Huxley (N-LAM-HH) circuit can effectively generate periodic and chaotic firing activities. Moreover, a PCB-based hardware circuit is physically implemented and experimental measurement is performed. The experimentally captured time-domain waveforms of chaotic and periodic firing activities well confirm the numerical explorations. These verify the feasibility of the LAM in characterizing Na + and K + channels and the availability of the N-LAM-HH circuit in generating firing activities, which can assist us in building the memristor-based neuromorphic hardware and exploring spike-based applications

Electromagnetic induction plays a crucial impact on the firing activity of biological neurons, since it exists along with the mutual effect between membrane potential and ions transport. Flux-controlled memristor is an available candidate in characterizing the electromagnetic induction effect. Different from the previously reported literature, a non-ideal flux-controlled memristor with cosine mem-conductance function is employed to determine the periodic magnetization and leakage flux processes in neurons. Thereafter, a three-dimensional (3D) memristive Wilson (m-Wilson) neuron model is constructed under the consideration of this kind of electromagnetic induction. Numerical simulations are performed by multiple numerical tools, which demonstrate that the 3D m-Wilson neuron model can generate abundant firing activities. Interestingly, coexisting firing activities, antimonotonicity, and firing frequency regulation are discovered under special parameter settings. Furthermore, a PCB-based analog circuit is designed and hardware measurements are executed to verify the numerical simulations. These explorations in numerical and hardware surveys might provide insights to regulate the firing activities by appropriate electromagnetic induction.

The gradual decline of nigral dopaminergic neurons is the main cause of Parkinson's disease (PD), yet as of now, there exists no conclusive therapeutic intervention. Glucagon-like peptide-1 (GLP-1) is an incretin, which is also a key substance regulating neuronal activity and synaptic transmission. GLP-1 receptors (GLP-1Rs) are widely expressed in the central nervous system. Chronic administration of low doses of 1-methyl-4-phenyl, 1,2,3,6-tetrahydropiridine (MPTP) mitigates mortality in mice during the modeling phase, thereby more closely mirroring the progression of PD. This study aims to observe the effects of GLP-1 receptor agonists (GLP-1RAs) on the firing activity of nigral dopaminergic neurons and motor behaviors in MPTP-induced chronic PD mice. Our findings revealed that peripheral administration of GLP-1RAs exendin-4 significantly alleviated motor impairments in MPTP-induced chronic PD mice. Concurrently, peripheral administration of exendin-4 increased the number of active dopaminergic neurons, improved the spontaneous firing activity, as well as alleviated MPTP-induced dopaminergic neuron loss in MPTP-induced PD mice. Furthermore, local administration of exendin-4 directly increased the firing rate of nigral dopaminergic neurons via GLP-1Rs, suggesting that peripheral administration of exendin-4 may exert neuroprotection through its mild excitation on dopaminergic neurons. These findings collectively imply that peripheral administration of GLP-1RAs may hold potential in the treatment of PD.

The glucagon-like peptide-1 (GLP-1) plays important roles in the regulation of food intake and energy metabolism. Peripheral or central GLP-1 suppresses food intake and reduces body weight. The electrophysiological properties of neurons in the mammalian central nervous system reflect the neuronal excitability and the functional organization of the brain. Recent studies focus on elucidating GLP-1-induced suppression of feeding behaviors and modulation of neuronal electrophysiological properties in several brain regions. Here, we summarize that activation of GLP-1 receptor (GLP-1R) suppresses food intake and induces postsynaptic depolarization of membrane potential and/or presynaptic modulation of glutamatergic or GABAergic neurotransmission in brain nuclei located within the medulla oblongata, pons, mesencephalon, diencephalon, and telencephalon. This review may provide a background to guide future research about the cellular mechanisms of GLP-1-induced feeding inhibition.

The aim of this work was to monitor the effects of extracellular α-synuclein on the firing activity of midbrain neurons dissociated from substantia nigra TH-GFP mice embryos and cultured on microelectrode arrays (MEA). We monitored the spontaneous firing discharge of the network for 21 days after plating and the role of glutamatergic and GABAergic inputs in regulating burst generation and network synchronism. Addition of GABA A , AMPA and NMDA antagonists did not suppress the spontaneous activity but allowed to identify three types of neurons that exhibited different modalities of firing and response to applied L-DOPA: high-rate (HR) neurons, low-rate pacemaking (LR-p), and low-rate non-pacemaking (LR-np) neurons. Most HR neurons were insensitive to L-DOPA, while the majority of LR-p neurons responded with a decrease of the firing discharge; less defined was the response of LR-np neurons. The effect of exogenous α-synuclein (α-syn) on the firing discharge of midbrain neurons was then studied by varying the exposure time (0–48 h) and the α-syn concentration (0.3–70 μM), while the formation of α-syn oligomers was monitored by means of AFM. Independently of the applied concentration, acute exposure to α-syn monomers did not exert any effect on the spontaneous firing rate of HR, LR-p, and LR-np neurons. On the contrary, after 48 h exposure, the firing activity was drastically altered at late developmental stages (14 days in vitro , DIV, neurons): α-syn oligomers progressively reduced the spontaneous firing discharge (IC 50 = 1.03 μM), impaired burst generation and network synchronism, proportionally to the increased oligomer/monomer ratio. Different effects were found on early-stage developed neurons (9 DIV), whose firing discharge remained unaltered, regardless of the applied α-syn concentration and the exposure time. Our findings unravel, for the first time, the variable effects of exogenous α-syn at different stages of midbrain network development and provide new evidence for the early detection of neuronal function impairment associated to aggregated forms of α-syn.

[This corrects the article DOI: 10.3389/fncel.2023.1078550.].

The biological effects of cannabinoids are mainly mediated by two members of the G-protein-coupled-receptor family: cannabinoid type 1 receptor (CB1R) and cannabinoid type 2 receptor (CB2R). Unlike CB1R, CB2R is considered a “peripheral” cannabinoid receptor. However, recent studies have found that CB2R is widely expressed in the central nervous system and is involved in dopamine related behavioral regulation, including dietary behavior, weight regulation, anxiety, and schizophrenia like behavior. Our previous laboratory research demonstrated that activating CB2R on dopaminergic neurons in the ventral tegmental area can regulate addictive behavior in animals by inhibiting neuronal excitability. However, it is currently unclear whether CB2R on dopaminergic neurons in the substantia nigra compacta (SNc) has similar therapeutic potential. Brain patch clamp results have shown that the CB2R agonist JWH133 significantly inhibits the discharge of SNc dopamine neurons in a concentration dependent manner. The pharmacological blocker AM630 of CB2R can reverse this inhibitory effect, indicating that the expression of CB2R in SNc dopaminergic neurons is functional. After treatment with JWH133, the number of induced action potentials decreased, and the peak potential interval time, action potential start time, and potential amplitude after hyperpolarization amplitude all increased. In addition, synaptic current results showed that JWH133 can significantly reduce the frequency of miniature excitatory postsynaptic currents, indicating that activating CB2R to some extent inhibits the release of presynaptic glutamate and indirectly excites postsynaptic neurons.

Mesenchymal stem cell (MSC) therapy shows promise in preclinical ischemic stroke models, yet clinical translation remains inconsistent. To address this gap, we investigated whether labeling MSCs with Ferucarbotran enables magnetic resonance imaging (MRI) tracking and enhances neural differentiation and functional integration, particularly focusing on the novel observation of spontaneous neuronal firing activity in transplanted cells. Rat MSCs (rMSCs) were transduced with red fluorescent protein (RFP) and labeled with Ferucarbotran to generate Fer-RFP⁺ rMSCs. These were transplanted into rats subjected to middle cerebral artery occlusion. MRI tracked cell migration and localization. Behavioral recovery was evaluated via the corner test, modified neurological severity score (mNSS), and infarct volume analysis. Post-transplantation, Fer-RFP⁺ rMSCs were magnetically isolated for ex vivo electrophysiological and immunocytochemical analyses. Ferucarbotran labeling did not impair rMSC viability and enhanced in vitro proliferation. MRI effectively visualized Fer-RFP⁺ rMSC migration to ischemic regions. Rats receiving Fer-RFP⁺ rMSCs showed significantly improved functional recovery and reduced infarct volumes compared to controls. Remarkably, ex vivo isolated Fer-RFP⁺ rMSCs exhibited spontaneous neuronal firing on multi-electrode array recordings and expressed the neuronal marker NeuN. Ferucarbotran-labeled MSCs not only serve as MRI-visible tracers but also exhibit neuronal electrophysiological properties post-transplantation in an ischemic stroke model. The emergence of spontaneous neuronal firing in ex vivo transplanted MSCs suggests functional neuronal differentiation, potentially underpinning the observed therapeutic effects. These findings offer new mechanistic insights into MSC-mediated stroke recovery and may enhance the translational relevance of MSC-based therapies.

The article focuses on the issue of a spatiotemporal excitable biophysical model that describes the propagation of electrical potential called spikes to model the diffusion-induced dynamics based on an analytical development of amplitude equations. Considering the Izhikevich neuron model consisting of coupled systems of ODEs, we demonstrate various results of spatiotemporal architecture (PDEs) using a suitable parameter regime. We analytically perform the saddle-node bifurcation and Hopf bifurcation analysis with bifurcating periodic solutions that show the transition phases in the system dynamics. We study different firing patterns both analytically and numerically by the formation of Riccati differential equation. To examine the characteristics of diffusive instabilities, we use Turing amplitude equations by multiscaling method. The instabilities and Turing bifurcation are established using theoretical analysis and numerical simulations. The spatial dynamics has potential effects on the deterministic system as a result of the diffusive matrices with various couplings, and the coupled oscillators with this nearest-neighbor coupling show synchronization measured by the synchronization factor analysis. Our results qualitatively reproduce different phenomena of the extended excitable system based with an efficient analytical scheme.

Anatomical studies have established the existence of reciprocal relationships between the main population of monoamine, serotonin (5-HT), norepinephrine (NE) and dopamine (DA) neurons in the brain. The present study was thus conducted to examine the firing activity of 5-HT and NE neurons in DA-depleted rats, as well as the firing activity of DA neurons in 5-HT- or NE-depleted rats. The selective lesion of DA neurons elicited by 6-hydroxydopamine (6-OHDA) decreased the spontaneous firing activity of dorsal raphe (DR) nucleus 5-HT neurons by 60%, thus revealing the excitatory effect of the DA input on these 5-HT neurons. In contrast, the selective lesion of 5-HT neurons produced by 5,7-dihydroxytryptamine (5,7-DHT) enhanced by 36% the firing activity of VTA DA neurons, thereby indicating an inhibitory effect of the 5-HT input on these DA neurons. With regard to the reciprocal interaction between DA and NE neurons, it was observed that the selective loss of DA neurons achieved by the intra-ventral tegmental area (VTA) injection of 6-OHDA increased the firing activity of a subset of locus coeruleus (LC) NE neurons by 47%. The selective loss of NE neurons in response to the intra-LC injection of 6-OHDA enhanced the firing activity of VTA DA neurons by 70%, demonstrating a net inhibitory role of the NE input on VTA DA neurons. These findings have important consequences for antidepressant treatments aimed at enhancing simultaneously 5-HT, NE and DA transmission. Indeed, based on the understanding of such interactions, it may be possible to develop strategies to improve the effectiveness of antidepressant drugs by preventing counter-productive negative feedback actions.