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T Sharp - One of the best experts on this subject based on the ideXlab platform.
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neurochemical and anatomical identification of fast and slow firing neurones in the rat dorsal raphe nucleus using juxtacellular labelling methods in vivo
Neuroscience, 2003Co-Authors: K A Allers, T SharpAbstract:Abstract GABA neurones in the dorsal raphe nucleus (DRN) influence ascending 5-hydroxytryptamine (5-HT) neurones but are not physiologically or anatomically characterised. Here, in vivo juxtacellular labelling methods in urethane-anaesthetised rats were used to establish the neurochemical and morphological identity of a fast-firing population of DRN neurones, which recent data suggest may be GABAergic. Slow-firing, putative 5-HT DRN neurones were also identified for the first time using this approach. Fast-firing, DRN neurones were successfully labelled with neurobiotin (n=10) and the majority (n=8/10) were immunoreactive for the GABA synthetic enzyme glutamic acid decarboxylase. These neurones were located in the DRN (mainly lateral regions), and consistently fired spikes with short width (1.1±0.1 ms) and high frequency (12.1±2.0 Hz). In most cases spike trains were regular but displayed low frequency oscillations (1–2 Hz). These neurones were morphologically heterogeneous but commonly had branching axons with varicosities and dendrites that extended across DRN subregions and the midline. Slow-firing DRN neurones were also successfully labelled with neurobiotin (n=24). These neurones comprised a population of neurones immunopositive for 5-HT and/or tryptophan hydroxylase (n=12) that fired broad spikes (2.2±0.2 ms) with high regularity and low frequency (1.7±0.2 Hz). However, a slow-firing, less regular population of neurones immunonegative for 5-HT/tryptophan hydroxylase (n=12) was also apparent. In summary, this study chemically identifies fast- and slow-firing neurones in the DRN and establishes for the first time that fast-firing DRN neurones are GABAergic. The electrophysiological and morphological properties of these neurones suggest a novel function involving co-ordination between GABA and 5-HT neurones dispersed across DRN subregions.
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in vivo inhibition of neuronal activity in the rat ventromedial prefrontal cortex by midbrain raphe nuclei role of 5 ht1a receptors
Neuropharmacology, 2003Co-Authors: Mihaly Hajos, S E Gartside, Viktor Sebestyen Varga, T SharpAbstract:Abstract The ventral part of the medial prefrontal cortex (mPFC) plays an important role in mood and cognition. This study examined the effect of the 5-HT in this region by measuring the electrophysiological response of ventral mPFC neurones to electrical stimulation of the dorsal and median raphe nuclei (DRN and MRN), which are the source of the 5-HT input. DRN or MRN stimulation evoked a consistent, short-latency, post-stimulus inhibition in the majority of ventral mPFC neurones tested (DRN: 44/73 neurones; MRN: 24/31 neurones). Some neurones responded to DRN or MRN stimulation with antidromic spikes indicating that they were mPFC-raphe projection neurones. Both DRN- and MRN-evoked inhibitions were attenuated by systemic administration of the 5-HT1A antagonist WAY 100635 (0.1 mg/kg i.v.). DRN-evoked inhibition was also attenuated by iontophoretic application of WAY 100635 and by systemic administration of the 5-HT1A antagonist, NAD-299 (4 mg/kg i.v.) but not the 5-HT2 antagonist ketanserin (4 mg/kg, i.v.). These data suggest that DRN and MRN 5-HT neurones inhibit neurones in the ventral mPFC via activation of 5-HT1A receptors. Some of these mPFC neurones may be part of a 5-HT1A receptor-controlled postsynaptic feedback loop to the DRN and MRN.
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Burst-firing activity of presumed 5-HT neurones of the rat dorsal raphe nucleus: electrophysiological analysis by antidromic stimulation.
Brain research, 1996Co-Authors: M Hajós, T SharpAbstract:We recently reported raphe neurones which frequently fired spikes in short bursts. However, the action potentials were broad and the neurones fired in a slow and regular pattern, suggesting they were an unusual type of 5-hydroxytryptamine (5-HT) neurone. In the present study, we investigated whether these putative burst-firing 5-HT neurones project to the forebrain and whether all spikes fired in bursts propagate along the axon. In anaesthetised rats, electrical stimulation of the medial forebrain bundle evoked antidromic spikes in both burst-firing neurones and in single-spiking, classical 5-HT neurones recorded in the dorsal raphe nucleus. Although the antidromic spike latency of the single-spiking and burst-firing neurones showed a clear overlap, burst-firing neurones had a significantly shorter latency than single-spiking neurones. For both burst-firing neurones and classical 5-HT neurones, antidromic spikes made collisions with spontaneously occurring spikes. Furthermore, in all burst-firing neurones tested, first, second and third order spikes in a burst could be made to collide with antidromic spike. Interestingly, in a small number of burst-firing neurones, antidromic stimulation evoked spike doublets, similar to those recorded spontaneously. From these data we conclude that burst-firing neurones in the dorsal raphe nucleus project to the forebrain, and each spike generated by the burst propagates along the axon and could thereby release transmitter (5-HT).
Jeffrey G. Tasker - One of the best experts on this subject based on the ideXlab platform.
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neurosecretory and non neurosecretory parvocellular neurones of the hypothalamic paraventricular nucleus express distinct electrophysiological properties
Journal of Neuroendocrinology, 2002Co-Authors: Jason A. Luther, S. S. Daftary, Cherif Boudaba, G. C. Gould, Cs K Halmos, Jeffrey G. TaskerAbstract:Parvocellular neurones of the hypothalamic paraventricular nucleus (PVN) comprise neurosecretory and non-neurosecretory subpopulations. We labelled neurosecretory neurones with intravenous injection of the retrograde tracer, fluoro-gold, and recorded from fluoro-gold-positive and negative PVN parvocellular neurones in hypothalamic slices. Non-neurosecretory parvocellular neurones generated a low-threshold spike (LTS) and robust T-type Ca2+ current, whereas neurosecretory neurones showed no LTS and a small T-current. LTS neurones were located in non-neurosecretory regions of the PVN, and non-LTS neurones were located in neurosecretory regions of the PVN. These findings indicate that neurosecretory and non-neurosecretory subtypes of parvocellular PVN neurones express distinct membrane electrical properties.
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voltage gated currents distinguish parvocellular from magnocellular neurones in the rat hypothalamic paraventricular nucleus
The Journal of Physiology, 2000Co-Authors: Jason A. Luther, Jeffrey G. TaskerAbstract:Magnocellular and parvocellular neurones of the hypothalamic paraventricular nucleus (PVN) differentially regulate pituitary hormone secretion and autonomic output. Previous experiments have suggested that magnocellular, or type I neurones, and parvocellular, or type II neurones, of the PVN express different electrophysiological properties. Whole-cell patch-clamp recordings were performed in hypothalamic slices to identify the voltage-gated currents responsible for the electrophysiological differences between type I and type II PVN neurones. Type I neurones, which display transient outward rectification and lack a low-threshold spike (LTS), generated a large A-type K+ current (IA) (mean ± s.e.m.: 1127.5 ± 126.4 pA; range: 250–3600 pA; voltage steps to −25 mV) but expressed little or no T-type Ca2+ current (IT). Type II neurones, which lack transient outward rectification but often display an LTS, expressed a smaller IA (360.1 ± 56.3 pA; range: 40–1100 pA; voltage steps to −25 mV), and 75 % of the type II neurones generated an IT (-402.5 ± 166.9 pA; range: −90 to −2200 pA; at peak). The voltage dependence of IA was shifted to more negative values in type I neurones compared to type II neurones. Thus, the activation threshold (-53.5 ± 0.9 and −46.1 ± 2.6 mV), the half-activation potential (-25 ± 1.9 and −17.9 ± 2.0 mV), the half-inactivation potential (-80.4 ± 9.3 and −67.2 ± 3.0 mV), and the potential at which the current became fully inactivated (-57.4 ± 2.1 and −49.8 ± 1.5 mV) were more negative in type I neurones than in type II neurones, respectively. IT in type II neurones activated at a threshold of −59.2 ± 1.2 mV, peaked at −32.6 ± 1.7 mV, was half-inactivated at −66.9 ± 2.2 mV, and was fully inactivated at −52.2 ± 2.2 mV. Both cell types expressed a delayed rectifier current with similar voltage dependence, although it was smaller in type I neurones (389.7 ± 39.3 pA) than in type II neurones (586.4 ± 76.0 pA). In type I neurones IA was reduced by 41.1 ± 7.0 % and the action potential delay caused by the transient outward rectification was reduced by 46.2 ± 10.3 % in 5 mm 4-aminopyridine. In type II neurones IT was reduced by 66.8 ± 10.9 % and the LTS was reduced by 76.7 ± 7.8 % in 100 μM nickel chloride, but neither IT nor LTS was sensitive to 50 μM cadmium chloride. Thus, differences in the electrophysiological properties between type I, putative magnocellular neurones and type II, putative parvocellular neurones of the PVN can be attributed to the differential expression of voltage-gated K+ and Ca2+ currents. This diversity of ion channel expression is likely to have profound effects on the response properties of these neurosecretory and non-neurosecretory neurones.
Allan E Herbison - One of the best experts on this subject based on the ideXlab platform.
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sex and sub region dependent modulation of arcuate kisspeptin neurones by vasopressin and vasoactive intestinal peptide
Journal of Neuroendocrinology, 2018Co-Authors: Danielle Schafer, Grace Kane, William H Colledge, Richard Piet, Allan E HerbisonAbstract:A population of kisspeptin neurones located in the hypothalamic arcuate nucleus (ARN) very likely represent the gonadotrophin-releasing hormone pulse generator responsible for driving pulsatile luteinising hormone secretion in mammals. As such, it has become important to understand the neural inputs that modulate the activity of ARN kisspeptin (ARNKISS ) neurones. Using a transgenic GCaMP6 mouse model allowing the intracellular calcium levels ([Ca2+ ]i ) of individual ARNKISS neurones to be assessed simultaneously, we examined whether the circadian neuropeptides vasoactive intestinal peptide (VIP) and arginine vasopressin (AVP) modulated the activity of ARNKISS neurones directly. To validate this methodology, we initially evaluated the effects of neurokinin B (NKB) on [Ca2+ ]i in kisspeptin neurones residing within the rostral, middle and caudal ARN subregions of adult male and female mice. All experiments were undertaken in the presence of tetrodotoxin and ionotropic amino acid antagonists. NKB was found to evoke an abrupt increase in [Ca2+ ]i in 95%-100% of kisspeptin neurones throughout the ARN of both sexes. By contrast, both VIP and AVP were found to primarily activate kisspeptin neurones located in the caudal ARN of female mice. Although 58% and 59% of caudal ARN kisspeptin neurones responded to AVP and VIP, respectively, in female mice, only 0%-8% of kisspeptin neurones located in other ARN subregions responded in females and 0%-12% of cells in any subregion in males (P < 0.05). These observations demonstrate unexpected sex differences and marked heterogeneity in functional neuropeptide receptor expression amongst ARNKISS neurones organised on a rostro-caudal basis. The functional significance of this unexpected influence of VIP and AVP on ARNKISS neurones remains to be established.
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dual phenotype kisspeptin dopamine neurones of the rostral periventricular area of the third ventricle project to gonadotrophin releasing hormone neurones
Journal of Neuroendocrinology, 2011Co-Authors: Jenny Clarkson, Allan E HerbisonAbstract:The neuropeptide kisspeptin and its G-protein-coupled receptor, Gpr54, are critical regulators of fertility. Two major populations of kisspeptin neurones exist in the rodent: one in the rostral periventricular area of the third ventricle (RP3V) and another in the arcuate nucleus. The RP3V population of kisspeptin neurones is crucial for the generation of the luteinising hormone surge that drives ovulation in females. The RP3V kisspeptin neurones are sexually dimorphic, with many more neurones in females than males, and they project to gonadotrophin-releasing hormone (GnRH) neurones. Tyrosine hydroxylase (TH) expressing neurones in the RP3V are also sexually dimorphic and are assumed to project to GnRH neurones. In the present study, we examined the coexpression of kisspeptin and TH peptides in the RP3V of dioestrous and pro-oestrous female mice. We also investigated whether kisspeptin and TH peptides colocalised in terminal appositions with GnRH neurones in the rostral preoptic area (rPOA). Approximately half of the kisspeptin neurones in the RP3V were found to also express TH and vice versa, although there was no difference between mice in dioestrus or pro-oestrus. The majority (95%) of GnRH neurones in the rPOA exhibited a close apposition from a kisspeptin fibre, whereas only one quarter exhibited a close apposition from a TH fibre. Many of the TH close appositions with GnRH neurones coexpressed kisspeptin (62-86%), although these dual-labelled appositions comprised <20% of all kisspeptin appositions on GnRH neurones. The percentage of GnRH neurones with kisspeptin, TH and double-labelled appositions did not differ between dioestrous and pro-oestrous mice. These findings indicate that a subpopulation of kisspeptin neurones expressing dopamine innervate GnRH neurones in the rPOA.
E Jankowska - One of the best experts on this subject based on the ideXlab platform.
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a trans spinal loop between neurones in the reticular formation and in the cerebellum
The Journal of Physiology, 2011Co-Authors: Ingela Hammar, P Krutki, H Drzymalacelichowska, E Nilsson, E JankowskaAbstract:Non-technicalsummary Voluntary limb movements are initiated in the brain but the neurones responsible for activating the muscles (motoneurones and interneurones) are located in the spinal cord. The spinal cord also contains neurones that provide the brain, and especially the cerebellum, with continuous information on effects of the descending commands. We show that one population of such neurones provide the cerebellum with information on how likely the brain's commands (mediated by descending reticulospinal neurones) are to be executed as planned, depending on the degree of inhibition of motoneurones. They may therefore play an important role in preventing errors in activation of motoneurones and thereby help the brain to correct its signals to the spinal cord before such errors have been committed. Abstract The study aimed to investigate the role that four populations of spinocerebellar neuro- nes play in forwarding information on descending commands relayed by feline reticulospinal neurones. Both intracellular and extracellular recording was used from medially located ventral spinocerebellartract(VSCT)neuronesaswellasfromspinalborder(SB)subpopulationofVSCT neurones and from dorsal spinocerebellar tract neurones located in Clarke's column (CC DSCT) and in the dorsal horn (dh DSCT) in the lumbosacral enlargement. Axons of reticulospinal neurones were stimulated within the ipsilateral and contralateral medial longitudinal fascicle (MLF). We found striking differences in synaptic input from reticulospinal neurones to these four populations of spinocerebellar neurones. Both monosynaptic and disynaptic excitatory input was found in VSCT and SB neurones, only disynaptic in CC DSCT neurones and none in dh DSCT neurones. Discharges of VSCT and SB neurones were potently modulated by inhibitory actions of group I and II afferents. Following application of single stimuli to peripheral nerves these neurones ceased to respond for about 5 ms and thereafter discharged at a lower incidence rate. As inhibition of spinocerebellar neurones and of α-motoneurones is evoked by the same premotor interneurones, VSCT neurones may provide the cerebellum with information on the likely outcome of reticulospinal actions on motoneurones depending on the degree to which they are inhibited. They may thereby enable the cerebellum to adjust descending commands relayed by reticulospinal neurones to the requirements of a given situation and thus prevent errors in the centrally initiated movements.
Paul P. Bertrand - One of the best experts on this subject based on the ideXlab platform.
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ATP participates in three excitatory postsynaptic potentials in the submucous plexus of the guinea pig ileum.
The Journal of Physiology, 2004Co-Authors: R. L. Monro, Paul P. Bertrand, Joel C. BornsteinAbstract:Synaptic transmission between neurones intrinsic to the wall of the intestine involves multiple neurotransmitters. This study aimed to identify neurotransmitters responsible for non-cholinergic excitatory synaptic transmission in the submucous plexus of the guinea pig ileum. Intracellular recordings were made from secretomotor and vasodilator neurones. A single electrical stimulus to a fibre tract evoked excitatory postsynaptic potentials (EPSPs) with three different time courses – fast, slow and an EPSP with an intermediate time course (latency 96 ms, duration 1.2 s). In all neurones, blocking nicotinic receptors reduced fast EPSPs, but they were abolished in only 57 of 78 neurones. Fast EPSPs were also reduced by P2 purinoceptor blockade (5 of 27 neurones) or 5-HT3 receptor blockade (3 of 20 neurones). The intermediate EPSP was abolished by P2 receptor blockade (13 of 13 neurones) or by the specific P2Y1 receptor antagonist MRS 2179 (5 of 5 neurones) and was always preceded by a nicotinic or mixed nicotinic/purinergic fast EPSP. Intermediate EPSPs were observed in over half of all neurones including most non-cholinergic secretomotor neurones identified by immunoreactivity for vasoactive intestinal peptide. The slow EPSP evoked by a single pulse stimulus was also abolished by P2 receptor blockade (5 of 5 neurones) or by MRS 2179 (3 of 3 neurones). We conclude that fast EPSPs in submucous neurones are mediated by acetylcholine acting at nicotinic receptors, ATP acting at P2X receptors and 5-HT acting at 5-HT3 receptors. Both the intermediate EPSP and the single stimulus slow EPSP are mediated by ATP acting at P2Y1 receptors
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evidence for functional nk1 tachykinin receptors on motor neurones supplying the circular muscle of guinea pig small and large intestine
Neurogastroenterology and Motility, 2000Co-Authors: Xiaochun Bian, Paul P. Bertrand, J B Furness, J C BornsteinAbstract:The guinea-pig intestine was investigated to determine which neurones are excited via NK1 receptors. The specific NK1 receptor agonists [Sar9, Met(O2)11]-SP and septide contracted the circular muscle of all regions via a tetrodotoxin (TTX)-insensitive mechanism. In the proximal colon, they also evoked a TTX-sensitive relaxation; in the distal colon, the contractions were larger when nerve impulses were blocked with TTX, indicating that the agonists excited inhibitory motor neurones. In the duodenum and ileum, TTX reduced agonist-evoked contractions indicating that excitatory motor neurones were activated. In the presence of indomethacin, TTX enhanced contractions of ileal circular muscle evoked by these agonists suggesting that NK1 receptors were on inhibitory motor neurones. Blockade of nitric oxide synthase (NOS) enhanced NK1 receptor agonist evoked contractions of duodenal circular muscle, indicating that the agonists excite inhibitory motor neurones in duodenum. Neurones immunoreactive for NK1 receptors were studied in the duodenum and distal colon. As reported previously for the ileum,1 some neurones were immunoreactive for NOS and had Dogiel type I morphology; features characteristic of inhibitory motor neurones. In conclusion, there are functional NK1 receptors on excitatory and inhibitory motor neurones in the guinea-pig small intestine and on inhibitory motor neurones in the colon.