Low-threshold, high-resolution, chronically stable intracortical microstimulation by ultraflexible electrodes.

Intracortical microstimulation (ICMS) enables applications ranging from neuroprosthetics to causal circuit manipulations. However, the resolution, efficacy, and chronic stability of neuromodulation are often compromised by adverse tissue responses to the indwelling electrodes. Here we engineer ultraflexible stim-nanoelectronic threads (StimNETs) and demonstrate low activation threshold, high resolution, and chronically stable ICMS in awake, behaving mouse models.

Low-threshold, high-resolution, chronically stable intracortical microstimulation by ultraflexible electrodes.

Intracortical microstimulation (ICMS) enables applications ranging from neuroprosthetics to causal circuit manipulations. However, the resolution, efficacy, and chronic stability of neuromodulation is often compromised by the adverse tissue responses to the indwelling electrodes. Here we engineer ultraflexible stim-Nanoelectronic Threads (StimNETs) and demonstrate low activation threshold, high resolution, and chronically stable ICMS in awake, behaving mouse models.

Characterization of functional subgroups among genetically identified cholinergic neurons in the pedunculopontine nucleus.

The pedunculopontine nucleus (PPN) is a part of the reticular activating system which is composed of cholinergic, glutamatergic and GABAergic neurons. Early electrophysiological studies characterized and grouped PPN neurons based on certain functional properties (i.e.

Author Correction: CB receptor activation induces intracellular Ca mobilization and 2-arachidonoylglycerol release in rodent spinal cord astrocytes.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

CB receptor activation induces intracellular Ca mobilization and 2-arachidonoylglycerol release in rodent spinal cord astrocytes.

Accumulating evidence supports the role of astrocytes in endocannabinoid mediated modulation of neural activity. It has been reported that some astrocytes express the cannabinoid type 1 receptor (CB-R), the activation of which is leading to Ca mobilization from internal stores and a consecutive release of glutamate. It has also been documented that astrocytes have the potential to produce the endocannabinoid 2-arachidonoylglycerol, one of the best known CB-R agonist.

Spike-Timing of Orbitofrontal Neurons Is Synchronized With Breathing.

The orbitofrontal cortex (OFC) has been implicated in a multiplicity of complex brain functions, including representations of expected outcome properties, post-decision confidence, momentary food-reward values, complex flavors and odors. As breathing rhythm has an influence on odor processing at primary olfactory areas, we tested the hypothesis that it may also influence neuronal activity in the OFC, a prefrontal area involved also in higher order processing of odors. We recorded spike timing of orbitofrontal neurons as well as local field potentials (LFPs) in awake, head-fixed mice, together with the breathing rhythm.

PRMT1 and PRMT8 regulate retinoic acid-dependent neuronal differentiation with implications to neuropathology.

Retinoids are morphogens and have been implicated in cell fate commitment of embryonic stem cells (ESCs) to neurons. Their effects are mediated by RAR and RXR nuclear receptors. However, transcriptional cofactors required for cell and gene-specific retinoid signaling are not known.

Endocannabinoid signaling modulates neurons of the pedunculopontine nucleus (PPN) via astrocytes.

The pedunculopontine nucleus (PPN) is known as the cholinergic part of the reticular activating system (RAS) and it plays an important role in transitions of slow-wave sleep to REM sleep and wakefulness. Although both exogenous and endocannabinoids affect sleep, the mechanism of endocannabinoid neuromodulation has not been characterized at cellular level in the PPN. In this paper, we demonstrate that both neurons and glial cells from the PPN respond to cannabinoid type 1 (CB1) receptor agonists.

The hyperpolarization-activated non-specific cation current (In ) adjusts the membrane properties, excitability, and activity pattern of the giant cells in the rat dorsal cochlear nucleus.

Giant cells of the cochlear nucleus are thought to integrate multimodal sensory inputs and participate in monaural sound source localization. Our aim was to explore the significance of a hyperpolarization-activated current in determining the activity of giant neurones in slices prepared from 10 to 14-day-old rats. When subjected to hyperpolarizing stimuli, giant cells produced a 4-(N-ethyl-N-phenylamino)-1,2-dimethyl-6-(methylamino) pyridinium chloride (ZD7288)-sensitive inward current with a reversal potential and half-activation voltage of -36 and -88 mV, respectively.

Three-dimensional reconstruction and quantitative morphometric analysis of pyramidal and giant neurons of the rat dorsal cochlear nucleus.

Correct interpretation of functional data obtained from various cell types of the cochlear nucleus (CN), a structure involved in auditory information processing, necessitates reliable cell identification. Our aim was to perform a quantitative morphological characterization of giant and pyramidal cells of the rat CN and identify parameters that are suitable for their adequate classification. Neurons were labeled with biocytin, visualized with a fluorescent marker, and three-dimensionally reconstructed from confocal images.

Protein phosphatase-1M and Rho-kinase affect exocytosis from cortical synaptosomes and influence neurotransmission at a glutamatergic giant synapse of the rat auditory system.

Protein phosphatase-1M (PP1M, myosin phosphatase) consists of a PP1 catalytic subunit (PP1c) and the myosin phosphatase target subunit-1 (MYPT1). RhoA-activated kinase (ROK) regulates PP1M via inhibitory phosphorylation of MYPT1. Using multidisciplinary approaches, we have studied the roles of PP1M and ROK in neurotransmission.

Activation of muscarinic receptors increases the activity of the granule neurones of the rat dorsal cochlear nucleus--a calcium imaging study.

Acetylcholine modulates the function of the cochlear nucleus via several pathways. In this study, the effects of cholinergic stimulation were studied on the cytoplasmic Ca(2+) concentration of granule neurones of the rat dorsal cochlear nucleus (DCN). Ca(2+) transients were recorded in Oregon-Green-BAPTA 1-loaded brain slices using a calcium imaging technique.

Targets, receptors and effects of muscarinic neuromodulation on giant neurones of the rat dorsal cochlear nucleus.

Although cholinergic modulation of the cochlear nucleus (CN) is functionally important, neither its cellular consequences nor the types of receptors conveying it are precisely known. The aim of this work was to characterise the cholinergic effects on giant cells of the CN, using electrophysiology and quantitative polymerase chain reaction. Application of the cholinergic agonist carbachol increased the spontaneous activity of the giant cells; which was partly the consequence of the reduction in a K(+) conductance.

Purkinje-like cells of the rat cochlear nucleus: a combined functional and morphological study.

Purkinje-like cells (PLCs) of the cochlear nucleus (CN) are strongly calbindin positive neurones with unknown function. In the present work functional and morphological methods have been employed to provide data about PLCs in general, and about their possible involvement in the synaptic organisation of the CN in particular. PLCs had slightly elongated soma, from which a complex dendritic arborisation extended with highly variable dimensions.

Cytoplasmic Ca(2+) concentration changes evoked by cholinergic stimulation in primary astrocyte cultures prepared from the rat cochlear nucleus.

The involvement of astrocytes in the cholinergic modulation of the cochlear nucleus has been studied using primary astrocyte cultures prepared from this nucleus. The cells were loaded with the membrane permeable form of the fluorescent Ca(2+) indicator Fluo-4, and carbachol-induced Ca(2+) concentration increases were monitored using an imaging system. In the presence of cholinergic stimulation 36.

Divergent cardiac effects of the first and second generation hypoglycemic sulfonylurea compounds.

The effects of first and second generation hypoglycemic sulfonylureas on the incidence of ventricular ectopic beats and on the duration of transitional ventricular fibrillation in the ischemic rat heart were investigated. First generation sulfonylurea compounds (tolbutamide, carbutamide and gliclazide) in 105 preparations increased, while second generation sulfonylurea compounds (glibenclamide and glipizide) in 50 preparations decreased in a dose-dependent manner both the number of ventricular ectopic beats and the duration of transitional ventricular fibrillation during the first 30 min after ligation of the left anterior descending coronary artery. Therefore, second generation sulfonylureas should be preferred in the treatment of type 2 diabetics with ischemic heart diseases, if satisfactory metabolic control cannot be achieved by a treatment regimen and diet alone.

Effects of first and second generation sulphonylureas on cardiotoxicity of strophanthidin in rabbits.

The effects of the first generation sulphonylurea compound gliclazide and the second generation sulphonylurea compound glipizide on strophanthidin toxicity was investigated in rabbits. The sulphonylurea pretreated animals were intravenously infused with 23 mumol/kg strophanthidin until the appearance of the first ventricular ectopic beat and continued thereafter until the appearance of ventricular fibrillation. The first generation sulphonylurea gliclazide increased, while the second generation sulphonylurea glipizide decreased the strophanthidin toxicity in a dose dependent manner.

Insulin induced reversibility of altered responsiveness in femoral arterial bed of diabetic dogs.

The altered reactivities of femoral arterial bed to noradrenaline, phenylephrine, adenosine and prostacyclin were compared in 18, clinically manifest but aketotic, alloxan diabetic mongrel dogs. Alloxan treatment markedly increased the vasoconstrictor responses to noradrenaline and phenylephrine, as well as the adenosine-induced vasodilation in the femoral vasculature. These changes were prevented or normalized, respectively, in the early or late insulin-treated alloxan diabetic animals.

Relationship between vascular adrenergic receptors and prostaglandin biosyntheses in canine diabetic coronary arteries.

Before the onset of histologically detectable alterations of diabetic arteries, a considerable decrease of vasodilation ability develops. The role of an altered prostaglandin biosynthesis in this phenomenon was investigated in connection to the altered vascular adrenergic mechanisms. The effect of phenylephrine on prostacyclin production of isolated coronary arterial rings (100 mumol/l) as well as on conductivity of the coronary arterial bed (7.

The effect of various hypoglycaemic sulphonylureas on the cardiotoxicity of glycosides and arrhythmogenic activity due to myocardial ischaemia.

The effects of different sulphonylureas on the electrical cardiac activity were studied in 145 rabbits and in 103 rats as well as in 278 digitalis-treated, non-smoker non-insulin-dependent diabetics on the same therapy at least during the previous three months. In rabbits and rats glibenclamide (0.0032-100 mumol.

Prostaglandins and altered diabetic vasoregulation.

In previous studies an enhanced tendency to vasconstriction could be demonstrated in special regions, first of all in the coronary arterial bed of the diabetic vasculature. Analysing the role of prostaglandins in this phenomenon, the present work demonstrates that in vivo the dose-dependent decrease in the conductivity of the coronary arterial bed induced by PGF2 alpha (3, 6, 12, 24, 48 nmol/kg) administration in alloxan- (560 mumol/kg) diabetic dogs (n = 6) proved to be more expressed after indomethacin (10 mumol/kg) treatment compared with metabolically healthy (n = 6) animals. In the presence of indomethacin (3 mumol/l) PGF2 alpha (1, 3, 10, 30 mumol/l) evoked also considerably higher vasoconstriction in the isolated coronary rings of the diabetic dogs in comparison to the metabolically healthy state.

Influence of diabetic state on coronary vasoregulation in myocardial hypoxia.

It is a matter of common knowledge that under ischaemic or hypoxic conditions the oxygen demand of the myocardium could only be satisfied by enhancement of collateral blood flow. It is demonstrated that in a diabetic state an elevation of the myocardial blood flow could not develop due to lack of proper vasodilation in the coronary arterial bed.

Effects of hypoxia and adrenergic stimulation induced alterations in PGI2 synthesis by diabetic coronary arteries.

Before the onset of histologically detectable alterations in diabetic arteries, a considerable decrease in vasodilatory potential is seen. While analyzing this phenomenon, the role of altered PGI2 synthesis in rings of coronary arteries from metabolically healthy and alloxan-diabetic dogs was measured by radioimmunoassay during baseline, under the influence of phenylephrine (100 mumol/L), and during hypoxia with or without the presence of the alpha adrenergic blocker phentolamine (5 mumol/L). Basal levels of PGI2 synthetized by healthy and diabetic coronaries were no different (7.

Effects of computer controlled submaximal glucose utilization on myocardial energy potential and on survival time during acute strophantin intoxication in dogs.

We checked the effect of a 4 hourly computer controlled submaximal glucose utilization (CCSGU) of 12.01 +/- 1.19 mg/kg min under normoglycaemic conditions and of a simultaneous diminishing of myocardial NEFA supply on trigger mechanism of ventricular fibrillation during acute strophantin intoxication (4 micrograms/kg min) in 17 mongrel dogs.