scholarly journals Transmitter and ion channel profiles of neurons in the primate abducens and trochlear nuclei

2021 ◽  
Author(s):  
Ümit Suat Mayadali ◽  
Jérome Fleuriet ◽  
Michael Mustari ◽  
Hans Straka ◽  
Anja Kerstin Ellen Horn
Keyword(s):  
Eye Movements ◽  
Ion Channel ◽  
Membrane Properties ◽  
Receptor Subtype ◽  
Receptor Subtypes ◽  
Voltage Gated ◽  
Calcium Ion Channels ◽  
Cell Type Specific ◽  
Transmitter Receptors ◽  
Intrinsic Membrane Properties

AbstractExtraocular motoneurons initiate dynamically different eye movements, including saccades, smooth pursuit and vestibulo-ocular reflexes. These motoneurons subdivide into two main types based on the structure of the neuro-muscular interface: motoneurons of singly-innervated (SIF), and motoneurons of multiply-innervated muscle fibers (MIF). SIF motoneurons are thought to provoke strong and brief/fast muscle contractions, whereas MIF motoneurons initiate prolonged, slow contractions. While relevant for adequate functionality, transmitter and ion channel profiles associated with the morpho-physiological differences between these motoneuron types, have not been elucidated so far. This prompted us to investigate the expression of voltage-gated potassium, sodium and calcium ion channels (Kv1.1, Kv3.1b, Nav1.6, Cav3.1–3.3, KCC2), the transmitter profiles of their presynaptic terminals (vGlut1 and 2, GlyT2 and GAD) and transmitter receptors (GluR2/3, NMDAR1, GlyR1α) using immunohistochemical analyses of abducens and trochlear motoneurons and of abducens internuclear neurons (INTs) in macaque monkeys. The main findings were: (1) MIF and SIF motoneurons express unique voltage-gated ion channel profiles, respectively, likely accounting for differences in intrinsic membrane properties. (2) Presynaptic glutamatergic synapses utilize vGlut2, but not vGlut1. (3) Trochlear motoneurons receive GABAergic inputs, abducens neurons receive both GABAergic and glycinergic inputs. (4) Synaptic densities differ between MIF and SIF motoneurons, with MIF motoneurons receiving fewer terminals. (5) Glutamatergic receptor subtypes differ between MIF and SIF motoneurons. While NMDAR1 is intensely expressed in INTs, MIF motoneurons lack this receptor subtype entirely. The obtained cell-type-specific transmitter and conductance profiles illuminate the structural substrates responsible for differential contributions of neurons in the abducens and trochlear nuclei to eye movements.

Role of metabotropic glutamate (ACPD) receptors at the parallel fiber-Purkinje cell synapse

1992 ◽  
Vol 68 (4) ◽  
pp. 1453-1462 ◽  
Author(s):  
S. R. Glaum ◽  
N. T. Slater ◽  
D. J. Rossi ◽  
R. J. Miller
Keyword(s):  
Purkinje Cell ◽  
Purkinje Cells ◽  
Parallel Fiber ◽  
Membrane Properties ◽  
Receptor Subtype ◽  
Receptor Subtypes ◽  
Fura 2 ◽  
Metabotropic Glutamate ◽  
Cell Synapse

1. The role of metabotropic glutamate receptors at the parallel fiber (PF)-Purkinje cell synapse in cerebellum was studied by examining the actions of the active stereoisomer (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid [1S,3R-ACPD (25-50 microM)] on fura-2-loaded, patch-clamped rat Purkinje cells in thin slices. 2. The bath application of 1S,3R-ACPD evoked a direct post-synaptic depolarization that readily desensitized during prolonged (> 1 min) applications of the drug. This depolarizing response to 1S,3R-ACPD differed from the slow depolarization to 1S,3R-ACPD observed in cortical neurons mediated via closure of potassium channels in that it was not associated with an obvious change in membrane conductance and was not blocked by external barium. Similarly, slow inward rectifier currents were not affected during the 1S,3R-ACPD-induced depolarization. 3. The direct depolarization induced by 1S,3R-ACPD was not mediated by N-methyl-D-aspartate (NMDA) or (RS)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid kainate (AMPA)-KA excitatory amino acid (EAA) receptor subtypes, because the response was not blocked in the presence of antagonists of these receptors. 4. The EAA antagonist L-2-amino-3-phosphonopropionic acid, which blocks 1S,3R-ACPD-induced inositide synthesis in other cell types, had no effect on the depolarizing response. 5. Fura-2 measurements of somatic [Ca2+]i revealed that [Ca2+]i was not elevated during the 1S,3R-ACPD-induced depolarization unless the cell fired calcium-dependent action potentials. 6. In addition to the direct depolarization induced by 1S,3R-ACPD, the amplitude of PF-evoked excitatory postsynaptic potentials (EPSPs) was profoundly and reversibly reduced. This effect was observed in all cells regardless of whether a direct depolarization was produced by 1S,3R-ACPD. This reduction of the PF EPSP generally preceded the onset of depolarizing responses, did not desensitize during prolonged applications of 1S,3R-ACPD, and was reversible. 7. The reversible reduction of the PF EPSP by 1S,3R-ACPD was not related to a postsynaptic blocking action of the drug, because responses of Purkinje cells to AMPA, an agonist of the EAA receptor subtype mediating the EPSP, were reversibly potentiated in the presence of 1S,3R-ACPD. 8. The nitric oxide synthesis promoter sodium nitroprusside (1-3 nM) had no effect on the amplitude of PF EPSP or the membrane properties of Purkinje cells.(ABSTRACT TRUNCATED AT 400 WORDS)

scholarly journals Opiate dependence induces cell type-specific plasticity of intrinsic membrane properties in the rat juxtacapsular bed nucleus of stria terminalis (jcBNST)

2017 ◽  
Vol 234 (23-24) ◽  
pp. 3485-3498 ◽  
Author(s):  
Walter Francesconi ◽  
Attila Szücs ◽  
Fulvia Berton ◽  
George F. Koob ◽  
Leandro F. Vendruscolo ◽  
...  
Keyword(s):  
Opiate Dependence ◽  
Membrane Properties ◽  
Stria Terminalis ◽  
Cell Type ◽  
Bed Nucleus ◽  
Cell Type Specific ◽  
Intrinsic Membrane Properties

Modulation of Spontaneous Firing in Rat Subthalamic Neurons by 5-HT Receptor Subtypes

2005 ◽  
Vol 93 (3) ◽  
pp. 1145-1157 ◽  
Author(s):  
Zixiu Xiang ◽  
Lie Wang ◽  
Stephen T. Kitai
Keyword(s):  
Receptor Antagonist ◽  
Receptor Agonist ◽  
Driving Forces ◽  
Brain Slices ◽  
Potassium Conductance ◽  
Firing Frequency ◽  
Membrane Properties ◽  
Receptor Subtype ◽  
Receptor Subtypes ◽  
Membrane Excitability

The subthalamic nucleus (STN) is considered to be one of the driving forces in the basal ganglia circuit. The STN is innervated by serotonergic afferents from the raphe nucleus and expresses a variety of 5-HT receptor subtypes. We investigated the effects of 5-HT and 5-HT receptor subtype agonists and antagonists on the firing properties of STN neurons in rat brain slices. We used cell-attached, perforated-patch, and whole cell recording techniques to detect changes in firing frequency and pattern and electrical membrane properties. Due to the depolarization of membrane potential caused by reduced potassium conductance, 5-HT (10 μM) increased the firing frequency of STN neurons without changing their firing pattern. Cadmium failed to occlude the effect of 5-HT on firing frequency. 5-HT had no effect on afterhyperpolarization current. These results indicated that the 5-HT action was not mediated by high-voltage–activated calcium channel currents and calcium-dependent potassium currents. 5-HT had no effect on hyperpolarization-activated cation current ( IH) amplitude and voltage-dependence of IH activation, suggesting that IH was not involved in 5-HT–induced excitation. The increased firing by 5-HT was mimicked by 5-HT2/4 receptor agonist α-methyl-5-HT and was partially mimicked by 5-HT2 receptor agonist DOI or 5-HT4 receptor agonist cisapride. The 5-HT action was partially reversed by 5-HT4 receptor antagonist SB 23597-190, 5-HT2 receptor antagonist ketanserin, and 5-HT2C receptor antagonist RS 102221. Our data indicate that 5-HT has significant ability to modulate membrane excitability in STN neurons; modulation is accomplished by decreasing potassium conductance by activating 5-HT4 and 5-HT2C receptors.

scholarly journals GRKs as Modulators of Neurotransmitter Receptors

Cells ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 52
Author(s):  
Eugenia V. Gurevich ◽  
Vsevolod V. Gurevich
Keyword(s):  
G Protein ◽  
General Model ◽  
G Protein Coupled Receptors ◽  
Receptor Internalization ◽  
Neurotransmitter Receptors ◽  
Receptor Subtype ◽  
Receptor Subtypes ◽  
Receptor Kinase ◽  
G Protein Coupled ◽  
Homologous Desensitization

Many receptors for neurotransmitters, such as dopamine, norepinephrine, acetylcholine, and neuropeptides, belong to the superfamily of G protein-coupled receptors (GPCRs). A general model posits that GPCRs undergo two-step homologous desensitization: the active receptor is phosphorylated by kinases of the G protein-coupled receptor kinase (GRK) family, whereupon arrestin proteins specifically bind active phosphorylated receptors, shutting down G protein-mediated signaling, facilitating receptor internalization, and initiating distinct signaling pathways via arrestin-based scaffolding. Here, we review the mechanisms of GRK-dependent regulation of neurotransmitter receptors, focusing on the diverse modes of GRK-mediated phosphorylation of receptor subtypes. The immediate signaling consequences of GRK-mediated receptor phosphorylation, such as arrestin recruitment, desensitization, and internalization/resensitization, are equally diverse, depending not only on the receptor subtype but also on phosphorylation by GRKs of select receptor residues. We discuss the signaling outcome as well as the biological and behavioral consequences of the GRK-dependent phosphorylation of neurotransmitter receptors where known.

scholarly journals Septohippocampal transmission from parvalbumin-positive neurons features rapid recovery from synaptic depression

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Feng Yi ◽  
Tavita Garrett ◽  
Karl Deisseroth ◽  
Heikki Haario ◽  
Emily Stone ◽  
...  
Keyword(s):  
Pyramidal Neurons ◽  
Synaptic Depression ◽  
Medial Septum ◽  
Membrane Properties ◽  
Projection Neurons ◽  
Calcium Dependent ◽  
Light Pulses ◽  
Diagonal Band ◽  
Initial Release ◽  
Intrinsic Membrane Properties

AbstractParvalbumin-containing projection neurons of the medial-septum-diagonal band of Broca ($$\hbox {PV}_{\text{MS-DBB}}$$ PV MS-DBB ) are essential for hippocampal rhythms and learning operations yet are poorly understood at cellular and synaptic levels. We combined electrophysiological, optogenetic, and modeling approaches to investigate $$\hbox {PV}_{\text{MS-DBB}}$$ PV MS-DBB neuronal properties. $$\hbox {PV}_{\text{MS-DBB}}$$ PV MS-DBB neurons had intrinsic membrane properties distinct from acetylcholine- and somatostatin-containing MS-DBB subtypes. Viral expression of the fast-kinetic channelrhodopsin ChETA-YFP elicited action potentials to brief (1–2 ms) 470 nm light pulses. To investigate $$\hbox {PV}_{\text{MS-DBB}}$$ PV MS-DBB transmission, light pulses at 5–50 Hz frequencies generated trains of inhibitory postsynaptic currents (IPSCs) in CA1 stratum oriens interneurons. Using a similar approach, optogenetic activation of local hippocampal PV ($$\hbox {PV}_{\text{HC}}$$ PV HC ) neurons generated trains of $$\hbox {PV}_{\text{HC}}$$ PV HC -mediated IPSCs in CA1 pyramidal neurons. Both synapse types exhibited short-term depression (STD) of IPSCs. However, relative to $$\hbox {PV}_{\text{HC}}$$ PV HC synapses, $$\hbox {PV}_{\text{MS-DBB}}$$ PV MS-DBB synapses possessed lower initial release probability, transiently resisted STD at gamma (20–50 Hz) frequencies, and recovered more rapidly from synaptic depression. Experimentally-constrained mathematical synapse models explored mechanistic differences. Relative to the $$\hbox {PV}_{\text{HC}}$$ PV HC model, the $$\hbox {PV}_{\text{MS-DBB}}$$ PV MS-DBB model exhibited higher sensitivity to calcium accumulation, permitting a faster rate of calcium-dependent recovery from STD. In conclusion, resistance of $$\hbox {PV}_{\text{MS-DBB}}$$ PV MS-DBB synapses to STD during short gamma bursts enables robust long-range GABAergic transmission from MS-DBB to hippocampus.

Reduced responses of retinal vessels of the newborn pig to prostaglandins but not to thromboxane

1994 ◽  
Vol 72 (2) ◽  
pp. 168-173 ◽  
Author(s):  
Daniel Abran ◽  
Daya R. Varma ◽  
Ding-You Li ◽  
Sylvain Chemtob
Keyword(s):  
Blood Flow ◽  
Receptor Agonist ◽  
Perfusion Pressure ◽  
Retinal Blood Flow ◽  
Receptor Subtype ◽  
Retinal Vasculature ◽  
Receptor Subtypes ◽  
Retinal Vessels ◽  
Limit Blood Flow ◽  
Arteries And Veins

The upper blood pressure limit of retinal blood flow autoregulation is lower in the newborn than in the adult; this suggests an insufficient vasoconstrictor response in the newborn when perfusion pressure is increased. Because prostaglandins (PGs) have an important role in autoregulation of retinal blood flow, we compared the effects of PGE2, PGF2α, carbacyclin (PGI2 analogue), and U46619 (thromboxane analogue), as well as that of agonists for the three different PGE2 receptor subtypes, 17-phenyl trinor PGE2 (EP1), butaprost (EP2), and M&B 28,767 (EP3), on the retinal vasculature of newborn and adult pigs, using isolated eyecup preparations. PGF2α and PGE2 caused a markedly greater constriction of retinal arteries and veins of the adult than of the newborn animals. Further analysis of the response to PGE2, using receptor subtype agonists, revealed that the EP1 receptor agonist, 17-phenyl trinor PGE2, and the EP3 receptor agonist, M&B 28,767, caused a significant constriction of adult arteries and veins but produced minimal effects on newborn vessels; the EP2 receptor agonist, butaprost, caused a small and comparable dilation of newborn and adult arteries and veins. The PGI2 analogue, carbacyclin, caused a greater dilation of the adult than of the newborn arteries, but produced comparable dilation of veins from both newborn and adult animals. In contrast to the effects of PGF2α and PGE2, the thromboxane analogue, U46619, as well as the α1-adrenoceptor agonist, phenylephrine, significantly constricted newborn arteries and veins, and this effect was comparable with that observed on retinal vessels of the adult. Our findings indicate that the retinal vasculature of the newborn responds minimally to prostaglandins, primarily PGF2α and PGE2, compared with the adult, but constricts effectively to thromboxane. Since prostaglandins play an important role in the autoregulation of retinal blood flow, our observations provide an explanation for the inability of the newborn to limit blood flow when perfusion pressure is raised.Key words: retinal vascular responses, prostaglandins, thromboxane, PGE2 receptor subtypes.

scholarly journals Galanin-receptor ligand M40 peptide distinguishes between putative galanin-receptor subtypes

1993 ◽  
Vol 90 (23) ◽  
pp. 11287-11291 ◽  
Author(s):  
T Bartfai ◽  
U Langel ◽  
K Bedecs ◽  
S Andell ◽  
T Land ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Binding Sites ◽  
Receptor Subtype ◽  
Receptor Subtypes ◽  
Galanin Receptor ◽  
Flexor Reflex ◽  
Receptor Ligand ◽  
Insulinoma Cells ◽  
Galanin Receptors

The galanin-receptor ligand M40 [galanin-(1-12)-Pro3-(Ala-Leu)2-Ala amide] binds with high affinity to [mono[125I]iodo-Tyr26]galanin-binding sites in hippocampal, hypothalamic, and spinal cord membranes and in membranes from Rin m5F rat insulinoma cells (IC50 = 3-15 nM). Receptor autoradiographic studies show that M40 (1 microM) displaces [mono[125I]iodo-Tyr26]galanin from binding sites in the hippocampus, hypothalamus, and spinal cord. In the brain, M40 acts as a potent galanin-receptor antagonist: M40, in doses comparable to that of galanin, antagonizes the stimulatory effects of galanin on feeding, and it blocks the galaninergic inhibition of the scopolamine-induced acetylcholine release in the ventral hippocampus in vivo. In contrast, M40 completely fails to antagonize both the galanin-mediated inhibition of the glucose-induced insulin release in isolated mouse pancreatic islets and the inhibitory effects of galanin on the forskolin-stimulated accumulation of 3',5'-cAMP in Rin m5F cells; instead M40 is a weak agonist at the galanin receptors in these two systems. M40 acts as a weak antagonist of galanin in the spinal flexor reflex model. These results suggest that at least two subtypes of the galanin receptor may exist. Hypothalamic and hippocampal galanin receptors represent a putative central galanin-receptor subtype (GL-1-receptor) that is blocked by M40. The pancreatic galanin receptor may represent another subtype (GL-2-receptor) that recognizes M40, but as a weak agonist. The galanin receptors in the spinal cord occupy an intermediate position between these two putative subtypes.

scholarly journals Characterisation of the Contribution of the GABA-Benzodiazepine α1 Receptor Subtype to [11C]Ro15-4513 PET Images

2012 ◽  
Vol 32 (4) ◽  
pp. 731-744 ◽  
Author(s):  
James FM Myers ◽  
Lula Rosso ◽  
Ben J Watson ◽  
Sue J Wilson ◽  
Nicola J Kalk ◽  
...  
Keyword(s):  
Spectral Analysis ◽  
A Priori ◽  
Benzodiazepine Receptor ◽  
Brain Regions ◽  
Complex Model ◽  
Receptor Subtype ◽  
Receptor Subtypes ◽  
Time Activity ◽  
Positron Emission ◽  
The Impact

This positron emission tomography (PET) study aimed to further define selectivity of [11C]Ro15-4513 binding to the GABARα5 relative to the GABARα1 benzodiazepine receptor subtype. The impact of zolpidem, a GABARα1-selective agonist, on [11C]Ro15-4513, which shows selectivity for GABARα5, and the nonselective benzodiazepine ligand [11C]flumazenil binding was assessed in humans. Compartmental modelling of the kinetics of [11C]Ro15-4513 time-activity curves was used to describe distribution volume ( VT) differences in regions populated by different GABA receptor subtypes. Those with low α5 were best fitted by one-tissue compartment models; and those with high α5 required a more complex model. The heterogeneity between brain regions suggested spectral analysis as a more appropriate method to quantify binding as it does not a priori specify compartments. Spectral analysis revealed that Zolpidem caused a significant VT decrease (~10%) in [11C]flumazenil, but no decrease in [11C]Ro15-4513 binding. Further analysis of [11C]Ro15-4513 kinetics revealed additional frequency components present in regions containing both α1 and α5 subtypes compared with those containing only α1. Zolpidem reduced one component (mean ± s.d.: 71% ± 41%), presumed to reflect α1-subtype binding, but not another (13% ± 22%), presumed to reflect α5. The proposed method for [11C]Ro15-4513 analysis may allow more accurate selective binding assays and estimation of drug occupancy for other nonselective ligands.

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