Imaging the induction and spread of seizure activity in the isolated brain of the guinea pig: the roles of GABA and glutamate receptors

1996 ◽  
Vol 76 (5) ◽  
pp. 3471-3492 ◽  
Author(s):  
P. Federico ◽  
B. A. MacVicar
Keyword(s):  
Guinea Pig ◽  
Receptor Antagonist ◽  
Glutamate Receptor ◽  
Entorhinal Cortex ◽  
Seizure Activity ◽  
Olfactory Cortex ◽  
Receptor Subtypes ◽  
Amygdaloid Nucleus ◽  
Field Potentials

1. The induction and spread of seizure activity was studied using imaging and electrophysiological techniques in the isolated whole brain of the guinea pig. We examined the role of GABA and glutamate receptor subtypes in controlling the spread of seizure activity across the olfactory cortex from a focus in the entorhinal cortex. Seizure spread was monitored by video imaging of intrinsic optical signals (reflectance changes) combined with multiple extracellular recordings. Both the unilateral and bilateral spread of seizure activity was monitored in different experiments. 2. Electrical stimulation of the lateral entorhinal cortex (10-15 V, 5 Hz, 5-10 s) evoked seizure activity that originated in the entorhinal cortex/hippocampus and later spread preferentially toward the posteromedial cortical amygdaloid nucleus ipsilaterally and bilaterally. The pattern of seizure spread in a given brain was highly reproducible. 3. The influence of gamma-aminobutyric acid (GABA) receptors on the spread of seizure activity was monitored at higher resolution on one side of the brain. Perfusion of a low concentration of the GABAA antagonist bicuculline methiodide (20 microM) resulted in spontaneous seizures that spread to the posteromedial cortical amygdaloid nucleus more rapidly than electrically evoked seizures [spread times: 5.5 +/- 3.7 s vs. 15.5 +/- 2.7 s, respectively (means +/- SE)]. Seizure spread was also more extensive in the presence of bicuculline involving the posterior perirhinal cortex and larger areas over the medial amygdala. Higher concentrations of bicuculline (100 microM) resulted in even more widespread propagation of spontaneous seizure activity throughout the olfactory cortex as well as to the perirhinal, insular, and occipital cortices. This concentration of bicuculline also further reduced the time required for seizure activity to spread from the entorhinal cortex to the posteromedial cortical amygdaloid nucleus (spread time = 2.3 +/- 1.7 s). The GABAB antagonist, CGP 35348 (200 microM), in contrast, had no significant effect of seizure induction or propagation. 4. The role of glutamate receptor subtypes in seizure propagation was studied by examining the bilateral spread of seizures. Perfusion of the kainate/alpha-amino-3-hydroxy-5-methyl-4-isoxazole proprionic acid (K/A) receptor antagonist (6-cyano-7-nitroquinoxaline-2,3-dione, CNQX, 20 microM) completely and reversibly suppressed stimulus-evoked seizure activity as detected electrophysiologically and optically. CNQX also reduced the magnitudes of field potentials recorded in the isolated brain in a reversible manner by an average of 70.8 +/- 2.21% of control. The N-methyl-D-aspartate (NMDA) receptor antagonist dibenzocyclohepteneimine (MK-801) did not significantly alter the magnitudes or shapes of field potentials recorded in the isolated brain nor did it significantly alter seizure activity measured optically or electrophysiologically. 5. Perfusion of the metabotropic glutamate receptor agonist [trans-1-amino-(IS,3R)-cyclopentanedicarboxylic acid (trans-ACPD), 150 microM] completely and reversibly suppressed stimulus-evoked seizure activity as detected electrophysiologically and optically. The magnitudes of field potentials recorded in the isolated brain also were reduced by trans-ACPD an average of 75.4 +/- 5.39% of control values. 6. These results demonstrate that GABAA-mediated transmission is functionally present and may play an important role in epileptic tissue in limiting the spread of seizure activity from the entorhinal cortex to the posteromedial cortical amygdaloid nucleus and in creating functional pathways or preferential routes of seizure spread. GABAB-mediated postsynaptic inhibition played no significant role in the induction or spread of seizure activity in this study. K/A receptors but not NMDA receptors are necessary for the induction and subsequent spread of seizure activity originating in the entorhinal cortex/hippocampus.

scholarly journals The Role of the Entorhinal Cortex in Extinction: Influences of Aging

2008 ◽  
Vol 2008 ◽  
pp. 1-8 ◽  
Author(s):  
Lia R. M. Bevilaqua ◽  
Janine I. Rossato ◽  
Juliana S. Bonini ◽  
Jociane C. Myskiw ◽  
Julia R. Clarke ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Entorhinal Cortex ◽  
Amyloid Plaques ◽  
Memory Formation ◽  
Amygdaloid Nucleus ◽  
Dependent Protein Kinase ◽  
Dependent Protein ◽  
Glutamate Nmda Receptors ◽  
The Brain

The entorhinal cortex is perhaps the area of the brain in which neurofibrillary tangles and amyloid plaques are first detectable in old age with or without mild cognitive impairment, and very particularly in Alzheimer's disease. It plays a key role in memory formation, retrieval, and extinction, as part of circuits that include the hippocampus, the amygdaloid nucleus, and several regions of the neocortex, in particular of the prefrontal cortex. Lesions or biochemical impairments of the entorhinal cortex hinder extinction. Microinfusion experiments have shown that glutamate NMDA receptors, calcium and calmodulin-dependent protein kinase II, and protein synthesis in the entorhinal cortex are involved in and required for extinction. Aging also hinders extinction; it is possible that its effect may be in part mediated by the entorhinal cortex.

Role of sulfate ester in influencing biologic activity of cholecystokinin-related peptides

1987 ◽  
Vol 252 (2) ◽  
pp. G178-G181 ◽  
Author(s):  
R. Vinayek ◽  
R. T. Jensen ◽  
J. D. Gardner
Keyword(s):  
Guinea Pig ◽  
Receptor Antagonist ◽  
Partial Agonist ◽  
Tyrosine Residue ◽  
Sulfate Ester ◽  
Rat Pancreas ◽  
Cck Receptors ◽  
Cholecystokinin Receptor ◽  
Cholecystokinin Receptors

In dispersed acini from guinea pig, mouse, or rat pancreas cholecystokinin-(27-33) is a full agonist, and removing the sulfate ester from the tyrosine residue in position 27 caused a 100- to 300-fold decrease in potency with no change in efficacy. In dispersed acini from mouse or rat pancreas, cholecystokinin-(27-32)-NH2 is a partial agonist, and removing the sulfate ester from the tyrosine in position 27 abolished the efficacy. The desulfated peptide was able, however, to interact with CCK receptors with a potency that was threefold less than that of cholecystokinin-(27-32)-NH2 and therefore functioned as a cholecystokinin receptor antagonist. In dispersed acini from guinea pig pancreas cholecystokinin-(27-32)-NH2 is a cholecystokinin receptor antagonist. Removing the sulfate ester from the tyrosine residue in position 27 of cholecystokinin(27-32)-NH2 caused a fourfold decrease in potency but did not abolish the ability of the peptide to interact with cholecystokinin receptors; therefore, desulfated cholecystokinin-(27-32)-NH2 functioned as a cholecystokinin receptor antagonist.

Role of NMDA, Non-NMDA, and GABA Receptors in Signal Propagation in the Amygdala Formation

2001 ◽  
Vol 86 (3) ◽  
pp. 1422-1429 ◽  
Author(s):  
C. Wang ◽  
W. A. Wilson ◽  
S. D. Moore
Keyword(s):  
Receptor Antagonist ◽  
Glutamate Receptor ◽  
Gaba Receptors ◽  
Critical Role ◽  
Signal Propagation ◽  
Central Nucleus ◽  
Complex Signals ◽  
Basolateral Nucleus ◽  
Nmda Glutamate Receptor

Although the synaptic physiology of the amygdala has been studied with single neuron recordings, the properties of the networks between the various nuclei have resisted characterization because of the limitations of field recording in a neuronally diffuse structure. We addressed this issue in the rat amygdala complex in vitro by using a photodiode array coupled with a voltage-sensitive dye. Low-intensity single pulse stimulation of the lateral amygdala nucleus produced a complex multi-phasic potential. This signal propagated to the basolateral nucleus and the amygdalostriatal transition zone but not to the central nucleus. The local potential, which depended on both synaptic responses and activation of voltage-dependent ion channels, was reduced in amplitude by the non– N-methyl-d-aspartate (non-NMDA) glutamate receptor antagonist 6,7-dinitroquinoxaline (DNQX) and reduced to a lesser extent by the NMDA glutamate receptor antagonistd-2-amino-5-phosphonovaleric acid (d-APV). We next characterized the less complex signals that propagated to more distal regions with or without the addition of the GABA receptor antagonist bicuculline (BIC). BIC alone greatly increased the signal propagation and permitted activation of previously silent areas within the amygdala. DNQX blocked signal propagation to amygdala regions outside of La, even in the presence of BIC, whereas d-APV had minimal effects on these distal signals. These data represent several novel findings: the characterization of the multi-component potential near the site of stimulation, the gating of signal propagation within the amygdala by GABAergic inhibition, the critical role of non-NMDA receptor–mediated depolarization in signal propagation, and the lack of a role for NMDA receptors in maintaining propagation.

Role of glutamate receptor subtypes in the lamprey respiratory network

1999 ◽  
Vol 826 (2) ◽  
pp. 298-302 ◽  
Author(s):  
Fulvia Bongianni ◽  
Tatiana G Deliagina ◽  
Sten Grillner
Keyword(s):  
Glutamate Receptor ◽  
Receptor Subtypes ◽  
Respiratory Network

scholarly journals The Role of NMDA Receptor Subtypes in Short-Term Plasticity in the Rat Entorhinal Cortex

2008 ◽  
Vol 2008 ◽  
pp. 1-13 ◽  
Author(s):  
Sophie E. L. Chamberlain ◽  
Jian Yang ◽  
Roland S. G. Jones
Keyword(s):  
Entorhinal Cortex ◽  
Glutamate Release ◽  
Receptor Subtypes ◽  
Short Term ◽  
Low Frequencies ◽  
Short Term Plasticity ◽  
Whole Cell Patch Clamp ◽  
Layer V ◽  
Presynaptic Nmda Receptors

We have previously shown that spontaneous release of glutamate in the entorhinal cortex (EC) is tonically facilitated via activation of presynaptic NMDA receptors (NMDAr) containing the NR2B subunit. Here we show that the same receptors mediate short-term plasticity manifested by frequency-dependent facilitation of evoked glutamate release at these synapses. Whole-cell patch-clamp recordings were made from layer V pyramidal neurones in rat EC slices. Evoked excitatory postsynaptic currents showed strong facilitation at relatively low frequencies (3 Hz) of activation. Facilitation was abolished by an NR2B-selective blocker (Ro 25-6981), but unaffected by NR2A-selective antagonists (Zn2+, NVP-AAM077). In contrast, postsynaptic NMDAr-mediated responses could be reduced by subunit-selective concentrations of all three antagonists. The data suggest that NMDAr involved in presynaptic plasticity in layer V are exclusively NR1/NR2B diheteromers, whilst postsynaptically they are probably a mixture of NR1/NR2A, NR1/NR2B diheteromers and NR1/NR2A/NR2B triheteromeric receptors.

Role of muscarinic M2 receptors in regulating beta-adrenergic responsiveness in maturing rabbit airway smooth muscle

1995 ◽  
Vol 269 (6) ◽  
pp. L783-L790 ◽  
Author(s):  
C. M. Schramm ◽  
N. C. Arjona ◽  
M. M. Grunstein
Keyword(s):  
Smooth Muscle ◽  
Receptor Antagonist ◽  
Airway Smooth Muscle ◽  
Smooth Muscle Contraction ◽  
Receptor Subtypes ◽  
Response Curves ◽  
Beta Adrenergic ◽  
Gi Protein ◽  
Functional Antagonism

Muscarinic M2 and M3 receptor subtypes have been pharmacologically distinguished in airway smooth muscle. Whereas M3 receptors have been associated with smooth muscle contraction, M2 receptors have been implicated in Gi protein-coupled inhibition of adenylyl cyclase. To determine whether the role of M2 receptors varies with age in tracheal smooth muscle (TSM), dose-dependent relaxation responses to isoproterenol were compared in TSM isolated from 3-day-old and adult rabbits precontracted with acetylcholine (ACh) in the absence (control) and presence of an M2 receptor antagonist (gallamine or methoctramine). From sustained half-maximal ACh contractions, adult TSM were 5.6-fold less sensitive than 3-day-old tissues to isoproterenol-induced relaxation. Furthermore, the magnitude of muscarinic functional antagonism of isoproterenol-mediated TSM relaxation, assessed by varying the initial degree of ACh-induced contraction, significantly increased with age. In gallamine- and methoctramine-treated tissues, the relaxation-response curves to isoproterenol were shifted to the left in both 3-day-old and adult TSM. In contrast, pretreatment with either M2 receptor antagonist had no significant effect on the magnitude of muscarinic functional antagonism at either age. Moreover, Western blot analysis of G alpha i common and specific subunit expression in TSM membranes demonstrated qualitatively similar levels in 3-day-old and adult TSM. Collectively, these findings provide new evidence that 1) there exist inherent age-dependent differences in both the airway relaxant responsiveness to beta-adrenoceptor stimulation and muscarinic functional antagonism of beta-adrenergic relaxation, and 2) the latter are attributed to mechanisms other than ontogenetic alteration in M2 receptor function or Gi protein expression in maturing rabbit TSM.

Role of 5-HT in cholera toxin-induced mucin secretion in the rat small intestine

1996 ◽  
Vol 270 (6) ◽  
pp. G1001-G1009 ◽  
Author(s):  
B. A. Moore ◽  
K. A. Sharkey ◽  
M. Mantle
Keyword(s):  
Small Intestine ◽  
Receptor Antagonist ◽  
Cholera Toxin ◽  
Receptor Subtypes ◽  
Rat Small Intestine ◽  
Mucin Secretion ◽  
Common Pathway ◽  
Distal Small Intestine ◽  
Intestinal Segments

We examined the role of 5-hydroxytryptamine (5-HT) in cholera toxin (CT)-induced mucin secretion in the proximal and distal regions of the rat small intestine. Neither the 5-HT2 receptor antagonist ketanserin nor the cyclooxygenase inhibitor indomethacin was capable of inhibiting choleraic mucin secretion. However, in the presence of the mixed 5-HT3/4 receptor antagonist tropisetron at doses that block both receptor subtypes, the secretory response was reduced to baseline levels in the proximal and distal small intestine. The selective 5-HT3 receptor antagonist ondansetron had no significant effect. These findings suggest that choleraic mucin secretion is mediated primarily through the activation of a 5-HT4-like receptor. Mucin secretion in response to the exogenous application of 5-HT occurs via two pathways: one is mediated by a 5-HT4-like receptor and is capsaicin sensitive but tetrodotoxin (TTX) insensitive, and one lacks the capsaicin-sensitive 5-HT4-mediated response but is TTX sensitive. Both converge on a common pathway that is cholinergic. No significant differences were observed between proximal and distal intestinal segments.

scholarly journals Dopamine Has Bidirectional Effects on Synaptic Responses to Cortical Inputs in Layer II of the Lateral Entorhinal Cortex

2006 ◽  
Vol 96 (6) ◽  
pp. 3006-3015 ◽  
Author(s):  
Douglas A. Caruana ◽  
Robert E. Sorge ◽  
Jane Stewart ◽  
C. Andrew Chapman
Keyword(s):  
Receptor Antagonist ◽  
Entorhinal Cortex ◽  
Piriform Cortex ◽  
Receptor Subtypes ◽  
Bath Application ◽  
Sensory Cortices ◽  
Dopamine Reuptake Inhibitor ◽  
Cortical Inputs ◽  
Synaptic Responses

Dopaminergic modulation of neuronal function has been extensively studied in the prefrontal cortex, but much less is known about its effects on glutamate-mediated synaptic transmission in the entorhinal cortex. The mesocortical dopamine system innervates the superficial layers of the lateral entorhinal cortex and may therefore modulate sensory inputs to this area. In awake rats, systemic administration of the dopamine reuptake inhibitor GBR12909 (10 mg/kg, ip) enhanced extracellular dopamine levels in the entorhinal cortex and significantly facilitated field excitatory postsynaptic potentials (fEPSPs) in layer II evoked by piriform cortex stimulation. An analysis of the receptor subtypes involved in the facilitation of evoked fEPSPs was conducted using horizontal slices of lateral entorhinal cortex in vitro. The effects of 15-min bath application of dopamine on synaptic responses were bidirectional and concentration dependent. Synaptic responses were enhanced by 10 μM dopamine and suppressed by concentrations of 50 and 100 μM. The D1-receptor antagonist SCH23390 (50 μM) blocked the significant facilitation of synaptic responses induced by 10 μM dopamine and the D2-receptor antagonist sulpiride (50 μM) prevented the suppression of fEPSPs observed with higher concentrations of dopamine. We propose here that dopamine release in the lateral entorhinal cortex, acting through D1 receptors, can lead to an enhancement of the salience of sensory representations carried to this region from adjacent sensory cortices.

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