Neuropharmacological mechanisms underlying rhythmical discharge in trigeminal interneurons during fictive mastication

1994 ◽  
Vol 71 (6) ◽  
pp. 2061-2073 ◽  
Author(s):  
T. Inoue ◽  
S. H. Chandler ◽  
L. J. Goldberg
Keyword(s):  
Nmda Receptor ◽  
Receptor Antagonist ◽  
Pulse Train ◽  
Short Pulse ◽  
Nmda Receptor Antagonist ◽  
Homocysteic Acid ◽  
Iontophoretic Application ◽  
Drive Signals ◽  
Train Stimulation ◽  
Stimulation Of

1. We have examined the effects of iontophoretic application of antagonists to excitatory amino acid (EAA) receptors, as well as glycine and gamma-aminobutyric acid (GABA), on rhythmically active (RA) brain stem neurons during cortically induced masticatory activity (RMA) in the anesthetized guinea pig. Ten of these neurons were antidromically activated at latencies of 0.3–0.9 ms by stimulation of the trigeminal motor nucleus (MoV). 2. RA neurons were divided into closer and opener type according to the phase of activation during RMA. Iontophoretic application of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), a specific non-N-methyl-D-aspartate (NMDA) receptor antagonist, suppressed discharge of both closer and opener type RA neurons during RMA. In contrast, iontophoretic application of 3-((1)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP), a specific NMDA receptor antagonist, was not effective in suppressing discharge of most opener type RA neurons but did reduce activity of closer type RA neurons. 3. Spike discharge of most RA neurons was time locked to each cortical stimulus during RMA. Some of the RA neurons were activated at a short latency to short pulse train stimulation of the cortex in the absence of RMA. In most cases CNQX reduced such time-locked responses during RMA and greatly reduced discharge evoked by short pulse stimulation of the cortex in all cases. In contrast, CPP was not as effective in suppressing either the time-locked responses during RMA or the discharge evoked by short pulse train stimulation of the cortex. 4. D,L-Homocysteic acid (HCA) application produced low level maintained discharge in RA neurons before RMA induction. When RMA was evoked in combination with HCA, rhythmical burst discharges with distinct interburst periods during the opening phase of RMA were observed in most closer type RA neurons. In contrast, during RMA in combination with HCA application, opener type RA neurons showed burst discharges that were modulated during the RMA cycle but lacked distinct interburst periods during the closer phase of the cycle. 5. During application of strychnine (STR), a glycine antagonist, discharge of closer type RA neurons increased in the opener phase of RMA during continuous HCA application. In contrast, bicuculline methiodide (BIC), a GABA antagonist, did not increase unit discharge of closer type RA neurons in the opener phase of RMA. 6. It is concluded that closer type RA neurons receive, alternatively, EAA-mediated excitatory and glycine-mediated inhibitory masticatory synaptic drive signals during RMA.(ABSTRACT TRUNCATED AT 400 WORDS)

Excitatory transmission in the basolateral amygdala

1991 ◽  
Vol 66 (3) ◽  
pp. 986-998 ◽  
Author(s):  
D. G. Rainnie ◽  
E. K. Asprodini ◽  
P. Shinnick-Gallagher
Keyword(s):  
Nmda Receptor ◽  
Receptor Antagonist ◽  
Nmda Antagonist ◽  
Receptor Activation ◽  
Nmda Receptor Antagonist ◽  
Current Injection ◽  
Membrane Hyperpolarization ◽  
Postsynaptic Potentials ◽  
The Mean ◽  
Stimulation Of

1. Intracellular current-clamp recordings obtained from neurons of the basolateral nucleus of the amygdala (BLA) were used to characterize postsynaptic potentials elicited through stimulation of the stria terminalis (ST) or the lateral amygdala (LA). The contribution of glutamatergic receptor subtypes to excitatory postsynaptic potentials (EPSPs) were analyzed by the use of the non N-methyl-D-aspartate (non-NMDA) antagonist, 6-cyano-7-nitro-quinoxaline-2,3-dione (CNQX), and the NMDA antagonist, (DL)-2-amino-5-phosphonovaleric acid (APV). 2. Basic membrane properties of BLA neurons determined from membrane responses to transient current injection showed that at the mean resting membrane potential (RMP; -67.2 mV) the input resistance (RN) and time constant for membrane charging (tau) were near maximal, and that both values were reduced with membrane hyperpolarization, suggesting an intrinsic regulation of synaptic efficacy. 3. Responses to stimulation of the ST or LA consisted of an EPSP followed by either a fast inhibitory postsynaptic potential (f-IPSP) only, or by a fast- and subsequent slow-IPSP (s-IPSP). The EPSP was graded in nature, increasing in amplitude with increased stimulus intensity, and with membrane hyperpolarization after DC current injection. Spontaneous EPSPs were also observed either as discrete events or as EPSP/IPSP waveforms. 4. In physiological Mg2+ concentrations (1.2 mM), at the mean RMP, the EPSP consisted of dual, fast and slow, glutamatergic components. The fast-EPSP (f-EPSP) possessed characteristics of kainate/quisqualate receptor activation, namely, the EPSP increased in amplitude with membrane hyperpolarization, was insensitive to the NMDA receptor antagonist, APV (50 microM), and was blocked by the non-NMDA receptor antagonist, CNQX (10 microM). In contrast, the slow-EPSP (s-EPSP) decreased in amplitude with membrane hyperpolarization, was insensitive to CNQX (10 microM), and was blocked by APV (50 microM), indicating mediation by NMDA receptor activation. 5. In the presence of CNQX (10 microM), ST stimulation evoked an APV-sensitive s-EPSP. In contrast, LA stimulation evoked a f-IPSP, which when blocked by subsequent addition of bicuculline methiodide (BMI; 30 microM) revealed a temporally overlapping APV-sensitive s-EPSP. These data suggest that EPSP amplitude and duration are determined, in part, by the shunting of membrane conductance caused by a concomitant IPSP. 6. Superfusion of either CNQX or APV in BLA neurons caused membrane hyperpolarization and blockade of spontaneous EPSPs and IPSPs, suggesting that these compounds may act to block tonic excitatory amino acid (EAA) release within the nucleus, and that a degree of feed-forward inhibition occurs within the nucleus.(ABSTRACT TRUNCATED AT 400 WORDS)

Role of the medullary lateral tegmental field in reflex-mediated sympathoexcitation in cats

2004 ◽  
Vol 286 (3) ◽  
pp. R451-R464 ◽  
Author(s):  
Hakan S. Orer ◽  
Gerard L. Gebber ◽  
Shaun W. Phillips ◽  
Susan M. Barman
Keyword(s):  
Nmda Receptor ◽  
Nmda Receptors ◽  
Receptor Antagonist ◽  
Sympathetic Nerve Activity ◽  
Nmda Receptor Antagonist ◽  
Vagal Afferents ◽  
Reflex Pathways ◽  
Excitatory Responses ◽  
Stimulation Of

We tested the hypothesis that blockade of N-methyl-d-aspartate (NMDA) and non-NMDA receptors on medullary lateral tegmental field (LTF) neurons would reduce the sympathoexcitatory responses elicited by electrical stimulation of vagal, trigeminal, and sciatic afferents, posterior hypothalamus, and midbrain periaqueductal gray as well as by activation of arterial chemoreceptors with intravenous NaCN. Bilateral microinjection of a non-NMDA receptor antagonist into LTF of urethane-anesthetized cats significantly decreased vagal afferent-evoked excitatory responses in inferior cardiac and vertebral nerves to 29 ± 8 and 24 ± 6% of control ( n = 7), respectively. Likewise, blockade of non-NMDA receptors significantly reduced chemoreceptor reflex-induced increases in inferior cardiac (from 210 ± 22 to 129 ± 13% of control; n = 4) and vertebral nerves (from 253 ± 41 to 154 ± 20% of control; n = 7) and mean arterial pressure (from 39 ± 7 to 21 ± 5 mmHg; n = 8). Microinjection of muscimol, but not an NMDA receptor antagonist, caused similar attenuation of these excitatory responses. Sympathoexcitatory responses to the other stimuli were not attenuated by microinjection of a non-NMDA receptor antagonist or muscimol into LTF. In fact, excitatory responses elicited by stimulation of trigeminal, and in some cases sciatic, afferents were enhanced. These data reveal two new roles for the LTF in control of sympathetic nerve activity in cats. One, LTF neurons are involved in mediating sympathoexcitation elicited by activation of vagal afferents and arterial chemoreceptors, primarily via activation of non-NMDA receptors. Two, non-NMDA receptor-mediated activation of other LTF neurons tonically suppresses transmission in trigeminal-sympathetic and sciatic-sympathetic reflex pathways.

Excitatory synaptic transmission in cultures of rat olfactory bulb

1990 ◽  
Vol 64 (2) ◽  
pp. 598-606 ◽  
Author(s):  
P. Q. Trombley ◽  
G. L. Westbrook
Keyword(s):  
T Cells ◽  
Nmda Receptor ◽  
Olfactory Bulb ◽  
Receptor Antagonist ◽  
Voltage Clamp ◽  
Nmda Receptor Antagonist ◽  
Half Width ◽  
Time To Peak ◽  
Stimulation Of ◽  
Olfactory Bulb Neurons

1. Olfactory bulb neurons were dissociated from neonatal rats and plated at low density on a confluent layer of olfactory bulb astrocytes. Intracellular stimulation of presumptive mitral/tufted (M/T) cells evoked monosynaptic excitatory postsynaptic potentials (EPSPs) in adjacent neurons. Whole-cell recording techniques and a flow-pipe drug delivery system were used to compare EPSPs with voltage-clamp recordings of currents evoked by excitatory amino acids (EAA) including N-acetylaspartylglutamate (NAAG), a putative mitral cell transmitter. 2. Cultured olfactory bulb neurons were morphologically and physiologically distinct. Large pyramidal-shaped neurons were present, which were NAAG immunoreactive; stimulation of these neurons invariably evoked EPSPs, suggesting that they were M/T cells. The majority of small bipolar neurons were glutamic acid decarboxylase (GAD) immunoreactive consistent with granule or periglomerular gamma-aminobutyric acid (GABA)ergic interneurons. 3. Monosynaptic EPSPs between M/T cells could be separated into fast and slow components by the use of EAA receptor antagonists. A fast component with a time-to-peak of 7.7 +/- 1.0 (SE) ms and half-width of 31.8 +/- 7.4 ms was blocked by the non-NMDA receptor antagonist 6-cyano-2,3-dihydroxy-7-nitro-quinoxaline (CNQX, 2.5 microM). The slow component (time-to-peak = 41.4 +/- 7.2 ms; half-width = 218.9 +/- 40.4 ms) was blocked by the N-methyl-D-aspartate (NMDA) receptor antagonist DL-2-amino-5-phosphonovaleric acid (AP5, 100 microM). 4. Under voltage clamp, flow-pipe applications of NAAG (10-1,000 microM) evoked inward currents at a holding potential of -60 mV in Mg-free solutions.(ABSTRACT TRUNCATED AT 250 WORDS)

Muscarinic Agonist–Induced Burst Firing in Immature Rat Olfactory Cortex Neurons In Vitro

1998 ◽  
Vol 79 (4) ◽  
pp. 2003-2012 ◽  
Author(s):  
M. Postlethwaite ◽  
A. Constanti ◽  
V. Libri
Keyword(s):  
Electrical Stimulation ◽  
Nmda Receptor ◽  
Receptor Antagonist ◽  
Epileptiform Activity ◽  
Nmda Receptor Antagonist ◽  
Olfactory Cortex ◽  
Muscarinic Agonist ◽  
Immature Rat ◽  
Stimulation Of

Postlethwaite, M., A. Constanti, and V. Libri. Muscarinic agonist–induced burst firing in immature rat olfactory cortex neurons in vitro. J. Neurophysiol. 79: 2003–2012, 1998. Age-related changes in pre-/postsynaptic muscarinic (mAChR) and metabotropic-glutamate (mGluR) responsiveness were studied in slices of olfactory cortex from both immature [postnatal day 16–22 ( P16–P22)] and adult (≥P40) rats, using a conventional intracellular recording technique. In adult neurons, bath application of the mAChR agonist oxotremorine-M (OXO-M; 10 μM), or the selective mGluR agonist 1-aminocyclopentane-1S-3R-dicarboxylic acid (1S,3R-ACPD; 10 μM) evoked sustained membrane depolarizations, increases in input resistance, intense repetitive firing, and the appearance of a slow poststimulus afterdepolarizing potential (sADP). Excitatory postsynaptic potentials (EPSPs) evoked by local electrical stimulation of association fiber terminals were also depressed. In contrast, in neurons from immature slices, the 10 μM OXO-M–induced membrane depolarization was followed by the appearance of spontaneous rhythmic epileptiform activity, which was voltage independent and reversible on drug wash out. Epileptiform bursts were abolished or reduced by coapplication of tetrodotoxin (1 μM), atropine (1 μM), pirenzepine (100–200 nM), the N-methyl-d-aspartate (NMDA) receptor antagonist dl-amino-5-phosphonovaleric acid (dl-APV; 100 μM), the non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 5–20 μM), the anesthetic-sedative barbiturate pentobarbitone (100 μM), or by raising the extracellular Mg2+ concentration, whereas a clear facilitatory effect was exhibited by the selective γ-aminobutyric acid-A (GABAA) receptor blocker (−)-bicuculline methiodide (10 μM). The epileptogenic effects induced by OXO-M were indistinguishable from those produced by 4-aminopyridine (4-AP; 100–200 μM), although these latter actions were unaffected by atropine. In slices from immature animals, electrical stimulation of layer III association fibers in the presence of 10 μM OXO-M was accompanied by a dramatic prolongation of evoked depolarizing postsynaptic potentials (PSPs), with the appearance of recurrent superimposed spike discharges. This effect was readily reversed on wash out of OXO-M. No comparable age-dependent differences were observed in the nature or time course of 1S,3R-ACPD–evoked pre- (or post)synaptic responses, even in immature cells where muscarinic epileptiform activity had previously been demonstrated. We suggest that the overall susceptibility toward muscarinic-induced epileptiform discharge in immature olfactory cortical neurons may depend on the functional integrity of presynaptic inhibitory mAChRs; additional contributing mechanisms were also considered.

An iontophoretic analysis of the pharmacologic mechanisms responsible for trigeminal motoneuronal discharge during masticatory-like activity in the guinea pig

1990 ◽  
Vol 63 (2) ◽  
pp. 356-369 ◽  
Author(s):  
N. Katakura ◽  
S. H. Chandler
Keyword(s):  
Amino Acid ◽  
Guinea Pig ◽  
Nmda Receptors ◽  
Pulse Train ◽  
Excitatory Amino Acid ◽  
Short Pulse ◽  
Drug Application ◽  
Cortical Stimulation ◽  
Iontophoretic Application ◽  
Train Stimulation

1. The effects of iontophoretic application of the excitatory amino acid antagonists kynurenic acid (KYN) and DL-2-amino-5-phosphonovaleric acid (APV), as well as the monoamines serotonin (5-HT) and norepinephrine (NE), on extracellularly recorded jaw opener motoneuron [digastric motoneuron (DIG)] discharge during cortically induced rhythmical masticatory-like activity (RMA) were examined in the anesthetized guinea pig. 2. Iontophoretic application of KYN, a broad-spectrum amino acid antagonist, suppressed the motoneuronal discharge evoked by short pulse train stimulation of the cortex for most cells tested. In contrast, iontophoretic application of APV, a specific N-methyl-D-aspartate (NMDA) antagonist, was usually without effect on the motoneuronal discharge evoked by short pulse train stimulation. 3. During RMA evoked by repetitive cortical stimulation, both KYN and APV suppressed rhythmical DIG motoneuronal discharge in many cells tested. 4. These data suggest that excitatory amino acid receptors on jaw opener motoneurons are involved in activation of RMA. It is proposed that the short-latency rapid excitation of jaw opener motoneurons, which occurs during both short pulse train cortical stimulation and RMA induced by repetitive cortical stimulation, is mediated, at least in part, by non-NMDA receptors. It is further suggested that the large-amplitude, long-duration slow rhythmical oscillations, which occur in the membrane potential of jaw opener motoneurons during RMA induced by repetitive cortical stimulation, are mediated, at least in part, by NMDA receptors. 5. Iontophoretic application of NE or 5-HT with low currents (less than 20 nA) produced a facilitation of digastric motoneuronal discharge during cycle-triggered glutamate application, short pulse train cortical stimulation, and RMA evoked by repetitive cortical stimulation. These facilitatory effects on motoneuronal discharge started within 1 min of drug application, reached a peak at approximately 3 min that persisted for several minutes after the application period, and recovered to control levels within 10-15 min. Direct application of NE or 5-HT, in the absence of chemical or synaptic activation, failed to activate these motoneurons. However, iontophoretic application of either monoamine could facilitate and bring to threshold rhythmical motoneuronal discharges during subthreshold repetitive cortical stimulation. 6. Iontophoretic application of methysergide, a 5-HT antagonist, and phentolamine, an alpha adrenoreceptor blocker, both produced a selective and reversible blockade of the facilitatory effects of 5-HT and NE, respectively, on motoneuronal discharge during cortically induced RMA. In contrast, iontophoretic application of sotalol, a beta adrenoreceptor blocker, had no effect on the NE-induced facilitation of RMA.(ABSTRACT TRUNCATED AT 400 WORDS)

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