A Prefrontal→Periaqueductal Gray Pathway Differentially Engages Autonomic, Hormonal, and Behavioral Features of the Stress-Coping Response.

The activation of autonomic and hypothalamo-pituitary-adrenal (HPA) systems occurs interdependently with behavioral adjustments under varying environmental demands. Nevertheless, laboratory rodent studies examining the neural bases of stress responses have generally attributed increments in these systems to be monolithic, regardless of whether an active or passive coping strategy is employed. Using the shock probe defensive burying test (SPDB) to measure stress-coping features naturalistically in male and female rats, we identify a neural pathway whereby activity changes may promote distinctive response patterns of hemodynamic and HPA indices typifying active and passive coping phenotypes.

GluD receptors are functional ion channels.

In this article, we review contemporary evidence that GluD receptors are functional ion channels whose depolarizing currents contribute to their biological functions, akin to all other members of the ionotropic glutamate receptor (iGluR) family.

Spatiotemporal Control of Noradrenaline-Dependent Synaptic Transmission in Mouse Dorsal Raphe Serotonin Neurons.

Activity of dorsal raphe neurons is controlled by noradrenaline afferents. In this brain region, noradrenaline activates Gα-coupled α1-adrenergic receptors (α1-A), causing action potential (AP) firing and serotonin release. , electrical stimulation elicits vesicular noradrenaline release and subsequent activation of α1-A to produce an EPSC (α1-A-EPSC).

Bidirectional flow of the funny current (I) during the pacemaking cycle in murine sinoatrial node myocytes.

Sinoatrial node myocytes (SAMs) act as cardiac pacemaker cells by firing spontaneous action potentials (APs) that initiate each heartbeat. The funny current (I) is critical for the generation of these spontaneous APs; however, its precise role during the pacemaking cycle remains unresolved. Here, we used the AP-clamp technique to quantify I during the cardiac cycle in mouse SAMs.

Excitation of medium spiny neurons by 'inhibitory' ultrapotent chemogenetics via shifts in chloride reversal potential.

Ultrapotent chemogenetics, including the chloride-permeable inhibitory PSAM-GlyR receptor, were recently proposed as a powerful strategy to selectively control neuronal activity in awake, behaving animals. We aimed to validate the inhibitory function of PSAM-GlyR in dopamine D1 receptor-expressing medium spiny neurons (D1-MSNs) in the ventral striatum. Activation of PSAM-GlyR with the uPSEM ligand enhanced rather than suppressed the activity of D1-MSNs in vivo as indicated by increased c-fos expression in D1-MSNs and in vitro as indicated by cell-attached recordings from D1-MSNs in mouse brain slices.

Control of food approach and eating by a GABAergic projection from lateral hypothalamus to dorsal pons.

Electrical or optogenetic stimulation of lateral hypothalamic (LH) GABA neurons induces rapid vigorous eating in sated animals. The dopamine system has been implicated in the regulation of feeding. Previous work has suggested that a subset of LH GABA neurons projects to the ventral tegmental area (VTA) and targets GABA neurons, inhibiting them and thereby disinhibiting dopaminergic activity and release.

Cell-Autonomous Excitation of Midbrain Dopamine Neurons by Endocannabinoid-Dependent Lipid Signaling.

The major endocannabinoid in the mammalian brain is the bioactive lipid 2-arachidonoylglycerol (2-AG). The best-known effects of 2-AG are mediated by G-protein-coupled cannabinoid receptors. In principle, 2-AG could modify neuronal excitability by acting directly on ion channels, but such mechanisms are poorly understood.

"Fungal elicitors combined with a sucrose feed significantly enhance triterpene production of a Salvia fruticosa cell suspension".

Oleanolic (OA) and ursolic acid (UA) are plant secondary metabolites with diverse pharmacological properties. To reach reasonable productivities with plant cell suspension cultures, elicitation is a widely used strategy. Within the presented work, the effects of different elicitors on growth and production of OA and UA in a Salvia fruticosa cell suspension culture were examined.

Depression of Serotonin Synaptic Transmission by the Dopamine Precursor L-DOPA.

Imbalance between the dopamine and serotonin (5-HT) neurotransmitter systems has been implicated in the comorbidity of Parkinson's disease (PD) and psychiatric disorders. L-DOPA, the leading treatment of PD, facilitates the production and release of dopamine. This study assessed the action of L-DOPA on monoamine synaptic transmission in mouse brain slices.

The rare DAT coding variant Val559 perturbs DA neuron function, changes behavior, and alters in vivo responses to psychostimulants.

Despite the critical role of the presynaptic dopamine (DA) transporter (DAT, SLC6A3) in DA clearance and psychostimulant responses, evidence that DAT dysfunction supports risk for mental illness is indirect. Recently, we identified a rare, nonsynonymous Slc6a3 variant that produces the DAT substitution Ala559Val in two male siblings who share a diagnosis of attention-deficit hyperactivity disorder (ADHD), with other studies identifying the variant in subjects with bipolar disorder (BPD) and autism spectrum disorder (ASD). Previously, using transfected cell studies, we observed that although DAT Val559 displays normal total and surface DAT protein levels, and normal DA recognition and uptake, the variant transporter exhibits anomalous DA efflux (ADE) and lacks capacity for amphetamine (AMPH)-stimulated DA release.

Spontaneous inhibitory synaptic currents mediated by a G protein-coupled receptor.

G protein-coupled receptors (GPCRs) affect many physiological processes by modulating both intrinsic membrane conductances and synaptic transmission. This study describes spontaneous miniature inhibitory postsynaptic currents mediated by vesicular dopamine release acting locally on metabotropic D2 receptors leading to the activation of a G protein-coupled inwardly rectifying potassium conductance. Thus, individual exocytotic events result in spontaneous GPCR-mediated transmission, similar to synaptic activation of classical ligand-gated ion channels.

Loss of Mecp2 in substantia nigra dopamine neurons compromises the nigrostriatal pathway.

Mutations in the methyl-CpG-binding protein 2 (MeCP2) result in Rett syndrome (RTT), an X-linked disorder that disrupts neurodevelopment. Girls with RTT exhibit motor deficits similar to those in Parkinson's disease, suggesting defects in the nigrostriatal pathway. This study examined age-dependent changes in dopamine neurons of the substantia nigra (SN) from wild-type, presymptomatic, and symptomatic Mecp2(+/-) mice.

Control of extracellular dopamine at dendrite and axon terminals.

Midbrain dopamine neurons release dopamine from both axons and dendrites. The mechanism underlying release at these different sites has been proposed to differ. This study used electrochemical and electrophysiological methods to compare the time course and calcium dependence of somatodendritic dopamine release in the ventral tegmental area (VTA) and substantia nigra pars compacta (SNc) to that of axonal dopamine release in the dorsal striatum.

CRF enhancement of GIRK channel-mediated transmission in dopamine neurons.

Dopamine neurons in the ventral midbrain contribute to learning and memory of natural and drug-related rewards. Corticotropin-releasing factor (CRF), a stress-related peptide, is thought to be involved in aspects of relapse following drug withdrawal, but the cellular actions are poorly understood. This study investigates the action of CRF on G-protein-linked inhibitory postsynaptic currents (IPSCs) mediated by GIRK (Kir3) channels in dopamine neurons.