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Cerebral Cortex (New York, N.Y. : 1991) May 2020Anatomical studies report a large proportion of fine myelinated fibers in the primate pyramidal tract (PT), while very few PT neurons (PTNs) with slow conduction...
Anatomical studies report a large proportion of fine myelinated fibers in the primate pyramidal tract (PT), while very few PT neurons (PTNs) with slow conduction velocities (CV) (<~10 m/s) are reported electrophysiologically. This discrepancy might reflect recording bias toward fast PTNs or prevention of antidromic invasion by recurrent inhibition (RI) of slow PTNs from faster axons. We investigated these factors in recordings made with a polyprobe (32 closely-spaced contacts) from motor cortex of anesthetized rats (n = 2) and macaques (n = 3), concentrating our search on PTNs with long antidromic latencies (ADLs). We identified 21 rat PTNs with ADLs >2.6 ms and estimated CV 3-8 m/s, and 67 macaque PTNs (>3.9 ms, CV 6-12 m/s). Spikes of most slow PTNs were small and present on only some recording contacts, while spikes from simultaneously recorded fast-conducting PTNs were large and appeared on all contacts. Antidromic thresholds were similar for fast and slow PTNS, while spike duration was considerably longer in slow PTNs. Most slow PTNs showed no signs of failure to respond antidromically. A number of tests, including intracortical microinjection of bicuculline (GABAA antagonist), failed to provide any evidence that RI prevented antidromic invasion of slow PTNs. Our results suggest that recording bias is the main reason why previous studies were dominated by fast PTNs.
Topics: Animals; Bicuculline; GABA-A Receptor Antagonists; Macaca; Motor Cortex; Neural Conduction; Neural Inhibition; Neurons; Pyramidal Tracts; Rats
PubMed: 32026928
DOI: 10.1093/cercor/bhz318 -
Archives of Razi Institute Apr 2022It is known that phoenixin-14 (PNX-14) has a mediatory role in reproduction; however, there is no report on the role of the PNX-14 on epilepsy. Therefore, this study...
It is known that phoenixin-14 (PNX-14) has a mediatory role in reproduction; however, there is no report on the role of the PNX-14 on epilepsy. Therefore, this study aimed to investigate the antiepileptic effects of the PNX-14 on the pentylenetetrazol (PTZ)-induced epilepsy in the stages of the estrous cycle among rats. A total of 168 adult female Wistar rats were randomly divided into seven groups, including control (intracerebroventricular injection was performed with saline), PNX-14 (5 µg), PNX-14 (10 µg), bicuculline (competitive antagonist of GABA receptors; 5 nmol)+PNX-14 (5 µg), bicuculline (BIC) (5 nmol)+PNX-14 (10 µg), saclofen (competitive antagonist of GABA receptors; 2.5 µg)+PNX-14 (5 µg), and saclofen (2.5 µg)+PNX-14 (10 µg) in proestrus, estrus, metestrus, and diestrus. Afterward, the control and treatment groups were followed by intraperitoneal administration of 80 mg/kg PTZ. Initiation time of myoclonic seizures (ITMS), initiation time of tonic-clonic seizures (ITTS), seizure duration (SD), and mortality rate (MR) were monitored and recorded for 30 min. According to the results, PNX-14 alone significantly reduced the SD and seizure mortality in all phases of estrus (<0.05). The injection of PNX-14 with BIC significantly reduced SD and seizure mortality in all estrus phases (<0.05). PNX-14 alone increased both ITMS and ITTS in all phases of estrus (<0.05). Furthermore, the injection of PNX-14 with BIC significantly reduced the effects of the PNX-14 on ITMS and ITTS in all estrus stages (<0.05). These results showed that the antiepileptic activity of PNX-14 was probably mediated by GABA receptors, and this effect was more prominent during the luteal phase than the follicular phase.
Topics: Animals; Female; Rats; Anticonvulsants; Baclofen; Bicuculline; Estrous Cycle; Pentylenetetrazole; Rats, Wistar; Seizures
PubMed: 36284939
DOI: 10.22092/ARI.2022.357297.2014 -
The Journal of Physiology Feb 19951. In order to determine whether GABAergic mechanisms are involved in the control of the milk ejection reflex in the rat, we examined the effects of central...
1. In order to determine whether GABAergic mechanisms are involved in the control of the milk ejection reflex in the rat, we examined the effects of central administration of a GABAA receptor agonist (muscimol) and antagonist (bicuculline) on the milk ejection reflex in the urethane-anaesthetized rat. 2. Intracerebroventricular (i.c.v.) injection of both muscimol (n = 17), at doses of 5, 10 and 20 ng, and bicuculline (n = 15), at doses of 0.01, 0.1 and 0.3 microgram, inhibited the milk ejection reflex in a dose-dependent manner. The bicuculline-induced inhibition was accompanied by desynchronization of the electroencephalogram and, at the highest dose, by alteration in the sensitivity of the mammary gland to oxytocin. No significant effect on the milk ejection reflex was seen with i.c.v. isotonic saline (n = 5). 3. Injection of 20 (n = 5) or 40 ng (n = 2) muscimol or 0.1 microgram bicuculline (n = 5) i.c.v. did not significantly alter the rise in intramammary pressure evoked by electrical stimulation of the neurohypophysis. 4. Bilateral 400 nl microinfusions directly into the supraoptic nuclei of either muscimol (20-100 ng microliter(-1); n = 10) or bicuculline (0.15 micrograms microliter(-1); n = 5) [corrected] resulted in an inhibition of the milk ejection reflex, which was not accompanied by desynchronization of the electroencephalogram. 5. The effects of i.c.v. injections of muscimol (15 and 20 ng) and bicuculline (0.01, 0.12 and 0.3 microgram) on the electrical activity of twenty-seven antidromically identified supraoptic magnocellular neurones were examined. Both compounds resulted in an inhibition of the background firing of oxytocinergic and vasopressinergic cells, and delayed the occurrence of high frequency bursts in oxytocin neurones. In five supraoptic neurones, bicuculline induced a transient activation before inhibition. 6. The powerful inhibitory action on the milk ejection reflex of both muscimol and bicuculline provides evidence for the importance of GABA neurones in maintaining the functional integrity of the mechanisms which allow the intermittent and pulsatile release of oxytocin during suckling.
Topics: Action Potentials; Animals; Bicuculline; Electric Stimulation; Electroencephalography; Female; Injections, Intraventricular; Mammary Glands, Animal; Milk Ejection; Muscimol; Neurons; Oxytocin; Pituitary Gland, Posterior; Rats; Rats, Wistar; Receptors, GABA; Reflex; Supraoptic Nucleus
PubMed: 7776233
DOI: 10.1113/jphysiol.1995.sp020579 -
Journal of Neurophysiology Mar 2016Interpretation of hemodynamic responses in epilepsy is hampered by an incomplete understanding of the underlying neurovascular coupling, especially the contributions of...
Interpretation of hemodynamic responses in epilepsy is hampered by an incomplete understanding of the underlying neurovascular coupling, especially the contributions of excitation and inhibition. We made simultaneous multimodal recordings of local field potentials (LFPs), firing of individual neurons, blood flow, and oxygen level in the somatosensory cortex of anesthetized rats. Epileptiform discharges induced by bicuculline injections were used to trigger large local events. LFP and blood flow were robustly coupled, as were LFP and tissue oxygen. In a parametric linear model, LFP and the baseline activities of cerebral blood flow and tissue partial oxygen tension contributed significantly to blood flow and oxygen responses. In an analysis of recordings from 402 neurons, blood flow/tissue oxygen correlated with the discharge of putative interneurons but not of principal cells. Our results show that interneuron activity is important in the vascular and metabolic responses during epileptiform discharges.
Topics: Animals; Bicuculline; Cerebrovascular Circulation; Epilepsy; Evoked Potentials, Somatosensory; Interneurons; Male; Oxygen Consumption; Rats; Rats, Wistar; Somatosensory Cortex
PubMed: 26745250
DOI: 10.1152/jn.00994.2014 -
Biomedical Research (Tokyo, Japan) 2023Seizure-like burst activities are induced by blockade of GABAA and/or glycine receptors in various spinal ventral roots of brainstem-spinal cord preparation from...
Seizure-like burst activities are induced by blockade of GABAA and/or glycine receptors in various spinal ventral roots of brainstem-spinal cord preparation from neonatal rodents. We found that this is not applicable to the phrenic nerve and that a new inhibitory descending pathway may suppress seizure-like activity in the phrenic nerve. Experiments were performed in brainstem-spinal cord preparation from newborn rats (age: 0-1 day). Left phrenic nerve and right C4 activities were recorded simultaneously. When GABAA and glycine receptors were blocked by 10 μM bicuculline and 10 μM strychnine (Bic+Str), seizure-like burst activities appeared in the fourth cervical ventral root (C4) but not the phrenic nerve. After making a transverse section at C1, the inspiratory burst activity disappeared from both C4 and the phrenic nerve, whereas seizure-like activity appeared in both nerves. We hypothesized that inhibitory descending pathways other than those via GABAA and/or glycine receptors (from the medulla to the spinal cord) work to avoid disturbance of regular respiratory-related diaphragm contraction by seizure-like activity. We found that cannabinoid receptor antagonist, AM251 was effective for the induction of seizure-like activity by Bic+Str in the phrenic nerve in brainstem-spinal cord preparation. Cannabinoid receptors may be involved in this descending inhibitory system.
Topics: Animals; Rats; Receptors, Glycine; Animals, Newborn; Receptors, Cannabinoid; Spinal Cord; Bicuculline; Strychnine; Seizures; Phrenic Nerve
PubMed: 37005282
DOI: 10.2220/biomedres.44.41 -
International Journal of Molecular... Dec 2022We examined the effects of an acute increase in blood pressure (BP) and renal sympathetic nerve activity (rSNA) induced by bicuculline (Bic) injection in the...
We examined the effects of an acute increase in blood pressure (BP) and renal sympathetic nerve activity (rSNA) induced by bicuculline (Bic) injection in the paraventricular nucleus of hypothalamus (PVN) or the effects of a selective increase in rSNA induced by renal nerve stimulation (RNS) on the renal excretion of sodium and water and its effect on sodium-hydrogen exchanger 3 (NHE3) activity. Uninephrectomized anesthetized male Wistar rats were divided into three groups: (1) Sham; (2) Bic PVN: (3) RNS + Bic injection into the PVN. BP and rSNA were recorded, and urine was collected prior and after the interventions in all groups. RNS decreased sodium (58%) and water excretion (53%) independently of BP changes (p < 0.05). However, after Bic injection in the PVN during RNS stimulation, the BP and rSNA increased by 30% and 60% (p < 0.05), respectively, diuresis (5-fold) and natriuresis (2.3-fold) were increased (p < 0.05), and NHE3 activity was significantly reduced, independently of glomerular filtration rate changes. Thus, an acute increase in the BP overcomes RNS, leading to diuresis, natriuresis, and NHE3 activity inhibition.
Topics: Rats; Animals; Male; Sodium; Sodium-Hydrogen Exchanger 3; Blood Pressure; Rats, Wistar; Kidney; Sympathetic Nervous System; Bicuculline
PubMed: 36613793
DOI: 10.3390/ijms24010349 -
The Journal of Physiology Apr 2019Spinal cord lamina I neurons receiving dense input from nociceptors and projecting to the parabrachial area at the ponto-mesencephalic junction form the major ascending...
KEY POINTS
Spinal cord lamina I neurons receiving dense input from nociceptors and projecting to the parabrachial area at the ponto-mesencephalic junction form the major ascending pain-related pathway in rodents. Lamina I spinoparabrachial (SPB) neurons have never been characterized in mice, despite the growing and extensive use of this species to understand the contribution of lamina I SPB neurons in chronic pain. The electrophysiological properties of lamina I SPB neurons recorded here in anaesthetized mice are comparable to those of rat or cat, forming a nociceptive and thermoreceptive pathway. It was confirmed 'on line' that lamina I SPB neurons that normally encode noxious stimuli can receive input from low threshold mechanoreceptors in certain conditions. The present work indicates that the study of lamina I SPB neurons in vivo could take advantage of the use of genetically modified mice.
ABSTRACT
Ongoing studies investigating the role of lamina I projection neurons in the generation of chronic pain are mainly based on the use of genetically modified mice. However, lamina I projection neurons have never been physiologically characterized in this species. The present work aimed to fill this gap, and to assess the effect of spinal 'disinhibition' that may occur in chronic pain states on the responses of these neurons to light touch. Seventy lamina I spinoparabrachial (SPB) neurons were characterized in anaesthetized mice. These neurons showed low central conduction velocities (<12.4 m s ) and wide range of responses. Fifty-six neurons responded equally to noxious mechanical and thermal (heat) stimuli (16% responded consistently to light touch). Modality-specific neurons responded preferentially to thermal (cold) stimuli (n = 10) and pinch (n = 2), or specifically to heat (n = 2). Spinal bicuculline and strychnine application induced responses to brush in half of the neurons tested, confirming directly the potential connection between low threshold mechanoreceptors and nociceptive-specific neurons, responsible for mechanical allodynia. Remarkably, the effect of the treatment was highly variable and apparently independent of the initial profile of the neurons. The present data confirm that mice lamina I SPB neurons have the expected characteristics to form a nociceptive and thermoreceptive pathway, but they constitute a highly heterogeneous group. The differential effect of spinal disinhibition observed here suggests that a subgroup of lamina I SPB neurons might be responsible for abnormal pain in pathological conditions, and emphasizes the importance of in vivo recording, a neglected approach.
Topics: Animals; Bicuculline; Convulsants; Male; Mechanotransduction, Cellular; Mice; Neurons; Spinal Cord Dorsal Horn; Strychnine; Thermosensing
PubMed: 30719699
DOI: 10.1113/JP277447 -
The Journal of Physiology Jan 1986Single neurones were recorded in the dorsal lateral geniculate nucleus (d.l.g.n.) of adult cats anaesthetized with a mixture of halothane, nitrous oxide and oxygen. The...
Single neurones were recorded in the dorsal lateral geniculate nucleus (d.l.g.n.) of adult cats anaesthetized with a mixture of halothane, nitrous oxide and oxygen. The multibarrel-glass micro-electrodes were filled with sodium acetate, L-glutamate, acetylcholine (ACh), gamma-aminobutyric acid (GABA) and bicuculline. In normally innervated, spontaneously active d.l.g.n. cells, ACh and L-glutamate elicited increased firing rates. After elimination of the excitatory input from the retina by retinal photocoagulation, the effects of ACh and L-glutamate were similar. This proves that both drugs have direct excitatory effects on d.l.g.n. cells and that disinhibition is not the most prominent influence of ACh in the d.l.g.n. The excitatory action of ACh on relay cells in the d.l.g.n. was strongly influenced by barbiturates. Sub-narcotic levels of sodium pentobarbitone completely abolished the excitation by ACh while the response to L-glutamate remained unchanged. Excitation, centre-surround antagonism and periphery effects were elicited by spots of light and by large field phase-reversing gratings with and without central sparing of the receptive field area. Binocular inhibition was elicited with the phase-reversing grating presented to the non-dominant eye. After localized destruction of the retinal receptive field area, retinogeniculate excitation ceased and an isolated lateral inhibition was observed in the acutely deafferented d.l.g.n. cells. The time course and strength of this inhibition was disclosed by raising the background discharge with microiontophoretically applied L-glutamate. With increasing size of retinal lesions the strength of isolated lateral inhibition decreased exponentially. A maximal intrageniculate range of more than 1000 microns was derived from computations of the lateral extent of deafferentation in the d.l.g.n. The inhibition acted beyond the classic surround inhibition of d.l.g.n. cells and thus was named long-range lateral inhibition. Microiontophoretically applied GABA elicits a strong inhibitory effect at the d.l.g.n. cells which is antagonized by bicuculline. Centre-surround antagonism, binocular inhibition and long-range inhibition were blocked by bicuculline and thus proven to be GABAergic. Each class of inhibition was differentially influenced by microiontophoretically applied ACh. Long-range inhibition was disinhibited, centre-surround antagonism was enhanced, and binocular inhibition was not significantly changed. In contrast to ACh excitation, the disinhibitory action of ACh was not suppressed by pentobarbitone.(ABSTRACT TRUNCATED AT 400 WORDS)
Topics: Acetylcholine; Action Potentials; Animals; Bicuculline; Cats; Cold Temperature; Geniculate Bodies; Glutamates; Glutamic Acid; Neural Inhibition; Neurons; Pentobarbital; Retinal Ganglion Cells; Time Factors; Visual Cortex; gamma-Aminobutyric Acid
PubMed: 2870178
DOI: 10.1113/jphysiol.1986.sp015932 -
ENeuro 2022Low-frequency (<200 Hz), subperception spinal cord stimulation (SCS) is a novel modality demonstrating therapeutic efficacy for treating chronic neuropathic pain. When...
Low-frequency (<200 Hz), subperception spinal cord stimulation (SCS) is a novel modality demonstrating therapeutic efficacy for treating chronic neuropathic pain. When stimulation parameters were carefully titrated, patients experienced rapid onset (seconds-minutes) pain relief without paresthesia, but the mechanisms of action are unknown. Using an integrated computational model and in vivo measurements in urethane-anesthetized rats, we quantified how stimulation parameters (placement, pulse width, frequency, and amplitude) influenced dorsal column (DC) axon activation and neural responses in the dorsal horn (DH). Both modeled and recorded DC axons responded with irregular spiking patterns in response to low-amplitude SCS. Maximum inhibition of DH neurons occurred at ∼80% of the predicted sensory threshold in both modeled and recorded neurons, and responses were strongly dependent on spatially targeting of stimulation, i.e., the complement of DC axons activated, and on stimulation parameters. Intrathecal administration of bicuculline shifted neural responses to low-amplitude stimulation in both the model and experiment, suggesting that analgesia is dependent on segmental GABAergic mechanisms. Our results support the hypothesis that low-frequency subperception SCS generates rapid analgesia by activating a small number of DC axons which inhibit DH neuron activity via surround inhibition.
Topics: Animals; Bicuculline; Neuralgia; Posterior Horn Cells; Rats; Spinal Cord; Spinal Cord Stimulation; Urethane
PubMed: 36150892
DOI: 10.1523/ENEURO.0058-22.2022 -
British Journal of Pharmacology Jul 19811 Interactions of depressant and anticonvulsant drugs with the neuronal gamma-aminobutyric acid (GABA) receptor + effector system have been examined on afferent fibres...
Distinction between the effects of barbiturates, benzodiazepines and phenytoin on responses to gamma-aminobutyric acid receptor activation and antagonism by bicuculline and picrotoxin.
1 Interactions of depressant and anticonvulsant drugs with the neuronal gamma-aminobutyric acid (GABA) receptor + effector system have been examined on afferent fibres to the rat cuneate nucleus in vitro. Three types of interaction have been measured: (a) potentiation of depolarizing responses to the GABA analogue, muscimol: (b) reduction in the potency of bicuculline as an antagonist of muscimol at the GABA receptor: (c) reduction in the potency of picrotoxin as an antagonist of muscimol acting on the effector mechanism. 2 Phenobarbitone reduced the potency of picrotoxin in doses which did not affect the potency of bicuculline and which caused only a small potentiation of muscimol. Pentobarbitone did not show such selectivity, a reduction in potency of picrotoxin always being accompanied by a reduction in potency of bicuculline and a substantial potentiation of muscimol. 3 Flurazepam and lorazepam both reduced the potency of picrotoxin without affecting that of bicuculline and with very little potentiation of muscimol. Phenytoin had no effect on the potency of picrotoxin whilst potentiating muscimol to the same extent as phenobarbitone. 4 The spectrum of drug activity in reducing the potency of picrotoxin correlates well with the reported anticonvulsant effects of these drugs against kindled amygdaloid seizures. Potentiation of muscimol and reduction of bicuculline potency appear more closely related to hypnotic properties.
Topics: Animals; Barbiturates; Benzodiazepines; Bicuculline; Dose-Response Relationship, Drug; Drug Interactions; Muscimol; Phenytoin; Picrotoxin; Rats; Receptors, Cell Surface; Receptors, GABA-A
PubMed: 6265019
DOI: 10.1111/j.1476-5381.1981.tb16810.x