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PubMed1988

Behavioral and physiological effects of trimethyltin in the rat hippocampus.

An injection of trimethyltin (TMT) into adult male Wistar rats produced a transient hyperirritability and aggressive behavior. When these effects of the drug subsided, the rats were still markedly impaired in performance of a spatial memory task examined in a watermaze. Activity of neurons in the hippocampus of these TMT-treated rats was studied in a slice preparation. A large (8 mg/kg) or double (7.5 and 3.5 mg/kg, two weeks apart) i.p. injection of TMT caused a loss of slow inhibitory postsynaptic potentials recorded in CA1 neurons in response to stimulation of stratum radiatum. A loss of accommodating properties of the neurons in response to a prolonged depolarizing current pulse was also seen in some of these cells. Other resting properties of the neurons were within the normal range. Topical application of acetylcholine (ACh) produces in normal hippocampal neurons a depolarizing response and a blockade of after-hyperpolarization. Only the latter response to ACh was seen in cells from TMT treated rats. No effect of the drug on reactivity to serotonin was detected. These effects of TMT were not seen when the drug was applied acutely while recording from cells in the slice indicating that it involves a degeneration process. These results suggest that the cognitive deficits in TMT treated rats might be associated with deficits in cholinergic functions.

Acetylcholine↗

PubMed1986

Hippocampal slices in experimental and human epilepsy.

Many models of epileptiform activity have been developed using in vitro slices, particularly the in vitro hippocampal slice preparation. Using this preparation, investigators have elucidated some of the intrinsic neuronal and synaptic properties that appear to be involved in the generation of burst activity and hyperexcitability typical of epileptic brain. A variety of potassium and calcium conductances, in dendritic as well as somatic membrane, have been found in hippocampal neurons that produce burst discharges; appropriate channel blockers can modulate the firing patterns of these neurons. Receptor antagonists, particularly those which interact with the gamma-aminobutyric acid (GABA) receptor-chloride channel complex, have also been found to be very effective in producing epileptiform activity in the reduced central nervous system (CNS) slice preparation. In most acutely produced epileptogenic slice tissues, it appears that blockade of inhibition, intrinsic mechanisms of excitability, and recurrent excitatory synaptic connections interact to synchronize the cell population. Slice preparations of brain tissue taken from epileptic foci induced in chronic animals have been studied. The kainic acid model, kindling model, and other chronic models of epileptiform activity (alumina gel, freeze lesions) have been studied in vitro; results of these studies suggest that in these tissues there is an alteration in PSP efficacy. Seizure sensitivity in immature CNS tissue may also be produced, in part, by a late development of inhibitory postsynaptic potentials (IPSPs). Studies of cortical slices taken from human epileptic brain during surgery for intractable seizures have begun to reveal some interesting clues about cellular mechanisms underlying discharge in abnormal tissue. Spontaneous, rhythmic post-synaptic potential (PSP) activity has been recorded particularly in slices taken from mesial temporal lobe structures involved in epileptic foci. It is still unclear, however, whether such activity is a reflection of epileptogenicity of this tissue, or is rather characteristic of even normal tissue from mesial temporal cortex. We have learned much about the cellular and synaptic properties of CNS neurons using the in vitro slice preparation and have developed a variety of animal preparations in which we can model epileptiform activity. However, it is still unclear if any of these preparations accurately model human epileptiform abnormalities. A major challenge for modern epilepsy research is to build a bridge between experimental animal models of epilepsy and the epilepsies that occur in the clinical human population.

Animals↗

PubMed1985

Mechanisms of sensory seizures: brain-stem neuronal response changes and convulsant drugs.

Generalized convulsive seizures can be triggered by sensory stimuli in animals treated with subthreshold levels of convulsant drugs. The sensory responses of the brain-stem reticular formation (RF) are extensively enhanced before seizure initiation with bicuculline, strychnine, pentylenetetrazol, physostigmine, and several other convulsants. The responses of RF neurons are more greatly enhanced than other nonprimary neurons in the hippocampus, amygdala, and cortex. The action of systemically administered convulsants involves direct effects on reticular neurons, because RF response enhancement is also seen with iontophoresis. RF neuronal response enhancement does not appear to involve actions of convulsants on specific neurotransmitters, because agents that act on different transmitters enhance the responses of the same RF neuron when given sequentially. Anticonvulsant drugs reverse the effects of convulsants on reticular neurons. The convulsant-induced response enhancement in the RF may involve blockade of inhibitory postsynaptic potentials and/or threshold reduction, effects observed in vitro. RF neurons may be most susceptible to convulsant action because these agents block habituation and other mechanisms that normally restrict RF neuronal responsiveness. The massive synchronization of reticular neuronal firing by sensory stimuli may induce seizures by intense output over widespread RF projection pathways analogous to the afterdischarge seizures seen with electrical stimulation of the RF.

Animals↗

PubMed1995

Postnatal development of synchronized network oscillations in the ferret dorsal lateral geniculate and perigeniculate nuclei.

Extracellular and intracellular recordings from slices of ferret dorsal lateral geniculate nucleus (LGNd) at postnatal ages P10-53 were performed to examine the postnatal development of spindle waves and the ability of block of GABAA receptors to alter these spindle waves into a slower, synchronous oscillation. As in prior studies in the adult, intracellular and extracellular recordings at ages P33-53 revealed robust spindle waves to be present in both the LGNd and perigeniculate nucleus (PGN). Intracellular recordings from thalamocortical relay cells in the A-laminae of the LGNd revealed that these cells received repetitive inhibitory postsynaptic potentials (IPSPs) at 6-9 Hz during the generation of spindle waves, and generated rebound low threshold Ca2+ spikes and bursts of 2-6 action potentials following each second or third IPSP. Intracellular recordings from the GABAergic neurons of the PGN at P33-53 revealed barrages of EPSPs that activated low threshold Ca2+ spikes and high frequency burst discharges of 2-10 action potentials during spindle wave generation. In contrast, full spindle waves were absent at ages prior to approximately P22 and spindle waves between the ages of P26 and approximately P30 were relatively weak and associated with only one or two action potentials per burst in both PGN neurons and LGNd relay cells. Bath application of the GABAA antagonist bicuculline methiodide at P41-53 resulted in a conversion of normal spindle waves into a marked 2-4 Hz oscillation in which the action potential firing of both thalamocortical relay and PGN neurons was greatly increased. In contrast, block of GABAA receptors prior to age P39 did not result in the generation of the slowed, 2-4 Hz network oscillation. Investigation of the electrophysiological properties of PGN neurons revealed that the postnatal development of spindle waves and bicuculline-induced slow oscillations were associated with an increase in the ability of PGN neurons to generate high frequency bursts of action potentials, suggesting that these changes in electrophysiological properties may contribute to the late development of synchronized oscillations in the ferret LGNd.

Aging↗

PubMed1993

Ethanol decreases glutamatergic synaptic transmission in rat nucleus accumbens in vitro: naloxone reversal.

The nucleus accumbens septi (NAcc) is a key brain region in the rewarding effects of addictive drugs such as opiates and ethanol. We recently showed that opiate peptides reduced both excitatory and inhibitory postsynaptic potentials (EPSPs and IPSPs) in NAcc neurons of a slice preparation, with naloxone (Nal) reversal (Yuan et al., 1992). To test other addictive drugs, we used intracellular recording in this rat NAcc slice preparation to investigate ethanol actions on NAcc neuronal properties. Ethanol 22 to 66 mM had little reproducible effect on membrane potential or input slope resistance, but reduced the amplitude of EPSPs evoked by stimulation of the peri-tubercle region ventral to NAcc. Ethanol 22, 44 and 66 mM all significantly decreased the EPSPs evoked by half-maximal stimulation to 80, 60 and 68% of control, respectively. Superfusion of 11 mM ethanol had no effect. To confirm a direct ethanol action on EPSPs, we tested 44 mM ethanol in the presence of 30 microM bicuculline to block IPSPs. In these cells ethanol still decreased EPSP size, suggesting GABAAergic IPSPs are not involved in this effect. The glutamate receptor blocker 6-cyano-7-nitroquinoxaline-2,3-dione abolished the EPSPs evoked at resting membrane potentials. As ethanol actions mimic those of opiates in reducing EPSPs without effect on resting membrane potentials in the NAcc, we applied the opiate antagonist Nal together with ethanol. Nal 1 to 2 microM significantly reversed ethanol (44 mM) reduction of EPSP amplitude. Thus, our data suggest that a major effect of intoxicating concentrations of ethanol in NAcc is to reduce glutamatergic synaptic transmission.(ABSTRACT TRUNCATED AT 250 WORDS)

Alcohol Deterrents↗

PubMed1977

[Mechanism of disorders of inhibition of electrogenesis in spinal alpha-motor neurons in experimental local botulin poisoning].

Disorders of postsynaptic inhibition and of the spinal cord alpha-motoneurons were studied in cats with experimental local botulinum intoxication. A significant decrease of the reciprocal, and, to a lesser extent, of polysynaptic inhibitory postsynaptic potential (IPSP) was noted. With the appearance of total paralysis of the muscles in the poisoned extremity there proved to be an even greater depression of the reciprocal and polysynaptic IPSP; however, they never disappeared or turned into depolarization potentials. Synaptic permeability of motor neurons as a rule decreased during the IPSP development, this indirectly indicating a reduction of ion transport.

Animals↗

PubMed1998

Effects of botulinum neurotoxin type A on the expression of gephyrin in cat abducens motoneurons.

In this study, we investigated the effects of long-term synaptic blockade on postsynaptic receptor clustering at central inhibitory glycinergic synapses. High doses of botulinum neurotoxin type A injected in the lateral rectus muscle completely abolishes inhibitory postsynaptic potentials onto abducens motoneurons within 2 days postinjection, and transmission remains blocked for at least 2 months. Using this model, we analyzed the expression of gephyrin, a glycine receptor clustering protein, on the membrane of motoneuron somata after botulinum neurotoxin type A injection in their target muscle. Immunofluorescence or electron microscopy immunohistochemistry revealed gephyrin-immunoreactive clusters (most < 0.5 microm in diameter) densely covering the surface of control abducens motoneurons. Ultrastructurally, presynaptic terminals containing flattened synaptic vesicles (F terminals) were found associated with multiple gephyrin-immunoreactive postsynaptic densities (average 1.24 gephyrin clusters/F+ profile). No significant changes in gephyrin-immunoreactive clusters were observed at 5 days postinjection, but we found significant reductions (25-40%) in the density of gephyrin clusters 19 and 35 days postinjection. Hence, the physiological alterations reported in this model precede structural changes on postsynaptic receptor cluster density. The decrease in gephyrin-immunoreactive clusters was paralleled by reductions in synaptic covering (F+ terminals per 100 microm of membrane). Presumed inactive F+ terminals that remained attached to the motoneuron surface displayed normal gephyrin-immunoreactive clusters; however, the pre- and postsynaptic membranes in between synaptic active zones frequently appeared separated by enlarged extracellular spaces. We concluded that postsynaptic receptor cluster dissolution seemed more directly related to terminal retraction than to inactivity alone.

Abducens Nerve↗

PubMed1999

Precocious development of parvalbumin-like immunoreactive interneurons in the hippocampal formation and entorhinal cortex of the fetal cynomolgus monkey.

The calcium-binding protein parvalbumin (PV), a reliable marker of the hippocampal basket and chandelier cells, is first expressed on embryonic day 83 (E83), corresponding to midgestation of the macaque monkey, in restricted hippocampal groups of immature neurons (Berger and Alvarez [1996] J. Comp. Neurol. 366:674-699). In the present study, PV-like immunoreactivity (LIR) was used to follow the further development of this subclass of interneurons. Asynchronous area-specific developmental sequences were observed, predominating initially in the caudal half of the hippocampal formation and the laterocaudal division of the entorhinal cortex and occurring relatively simultaneously in the interconnected hippocampal and entorhinal subfields. Dendritic elongation of PV-like immunoreactive interneurons and perisomatic distribution of PV-like immunoreactive terminal boutons on their cellular targets were first observed in the subiculum around E127; then from E127 to E142 in CA3/CA2 and layers III-V of the entorhinal cortex and, to a lesser extent in CA1, the dentate hilus and deep granule cell layer; and finally from E156 to postnatal day 12 in the rest of the dentate gyrus, the presubiculum and parasubiculum, and layers III-II-I of the entorhinal cortex. These data provide the first indication that a population of basket cells, a major gamma-aminobutyric acid (GABA)ergic component of the hippocampal intrinsic inhibitory circuitry, reaches its cellular targets several weeks before birth in primates in contrast to rodents. The role of the prenatal PV expression in the hippocampal formation of nonhuman primates and whether it coincides with the onset of postsynaptic inhibitory potentials or is accompanied or preceded by a period of gamma-aminobutyric acid-mediated excitatory effects as in rat pups, are crucial questions. They underline the need to pursue direct investigations on primates to be able to legitimately extrapolate the data obtained in rodents.

Aging↗

PubMed1999

Characterization of G-protein-gated K+ channels composed of Kir3.2 subunits in dopaminergic neurons of the substantia nigra.

G-protein-gated K+ (KG) channels generate slow inhibitory postsynaptic potentials in the brain. Current opinion suggests that neuronal KG channels are heterotetramers of Kir3.1 and Kir3.2. In substantia nigra (SN), however, mRNA of Kir3.1 does not express, whereas that of Kir3.2 clearly does. Therefore, we have characterized the KG channels containing Kir3.2 subunits in SN using biochemical and immunological techniques. We found that they were composed of only Kir3.2 subunits and did not contain significant amounts of either Kir3.1 or Kir3.3. Furthermore, at least some of the KG channels in SN were assemblies of the splicing variants Kir3. 2a and Kir3.2c. The channels were localized specifically at the postsynaptic membrane on the dendrites of dopaminergic neurons. Kir3. 2c, but not Kir3.2a, could bind a PDZ domain-containing protein, PSD-95. The heterologously expressed KG channels composed of Kir3.2a plus Kir3.2c or Kir3.2a alone were activated by G-protein stimulation, but expression of Kir3.2c alone was not. This study reveals that the Kir3.2 splicing variants play distinct roles in the control of function and localization of some of the KG channels in dopaminergic neurons of SN.

Animals↗

PubMed1988

Responses of rat lateral hypothalamic neuron activity to dorsal raphe nuclei stimulation.

1. The effects of dorsal raphe (DR) stimulation on neural activity in the rat lateral hypothalamic area (LHA), including specific glucose-sensitive neurons, were investigated by extracellular and intracellular recording in vivo, and the neurotransmitters involved were determined. 2. In 67 adult male anesthetized rats, 287 extracellular and 49 intracellular recordings of LHA responses to electrical stimulation of the DR were examined. 3. To determine neurotransmitter candidates, the effects of serotonin and the serotonin antagonists methysergide, lisuride, and (-)-propranolol were investigated by systemic administration and microelectrophoresis. 4. Of 287 spontaneously firing LHA neurons tested by DR stimulation, 157 (55%) were inhibited. Among these, 51% were glucose sensitive. The serotonin 1 receptor antagonists, lisuride and (-)-propranolol, attenuated the inhibitory responses to both DR stimulation and electrophoretic serotonin application. 5. Seventy-three (25%) were excited by DR stimulation, and 71% of these were glucose insensitive. Methysergide attenuated the excitatory responses to DR stimulation and the inhibitory response to electrophoretic serotonin application, but (-)-propranolol did not attenuate the excitation. 6. Intracellular recordings of LHA neurons during DR stimulation showed monosynaptic excitatory postsynaptic potentials (EPSPs) or inhibitory postsynaptic potentials (IPSPs) with 3.8 and 3.0 ms latency, respectively. The reversal potential for the former was approximately -17 and for the latter, -94 mV. 7. From the results we concluded that 75% of LHA glucose-sensitive neurons receive inhibitory serotonin inputs from the DR through serotonin 1 receptors, and 20% of glucose-insensitive neurons receive excitatory inputs from the DR through serotonin 2 receptors though 41% of these receive inhibitory inputs through serotonin 1 receptor.

Action Potentials↗

PubMed1987

Corticofugal inhibitory effects on lingually induced postsynaptic potentials in cat hypoglossal motoneurons.

The suppression of lingually or cortically induced postsynaptic potentials produced by conditioning stimulation of the cerebral cortex or the lingual nerve was studied in cat hypoglossal motoneurons. We have demonstrated that lingually or cortically induced inhibitory postsynaptic potentials were effectively suppressed by a conditioning stimulus of the cerebral cortex or the lingual nerve. In hypoglossal motoneurons after blocking inhibitory postsynaptic potentials by the administration of strychnine, lingually induced excitatory postsynaptic potentials and spikes were effectively suppressed by cortical stimulation. Whereas, a conditioning stimulus of the lingual nerve suppressed only a long-latency excitatory postsynaptic potential evoked by a test stimulus of the cerebral cortex, while a short-latency excitatory postsynaptic potential was unaffected. Picrotoxin and bicuculline appeared to act by reducing the suppression of lingually induced excitatory postsynaptic potentials produced by cortical conditioning stimulation.

Action Potentials↗

PubMed1991

Postsynaptic potentials mediated by excitatory and inhibitory amino acids in interneurons of stratum pyramidale of the CA1 region of rat hippocampal slices in vitro.

1. Because interneurons of stratum pyramidale partly mediate the feed-forward inhibition of pyramidal cells, intracellular postsynaptic potentials (PSPs) evoked by activation of afferent fibers were examined in 32 nonpyramidal cells of stratum pyramidale of the CA1 region of rat hippocampal slices. 2. Electrical stimulation of stratum radiatum at the CA1-CA3 border elicited, in interneurons, PSPs that were composed of four components: a fast excitatory postsynaptic potential (EPSP), an early inhibitory postsynaptic potential (IPSPA), a late IPSPB, and in some cells a delayed, slower EPSP. These synaptic potentials summated and elicited single action potentials in 57% of cells (17/30) and burst of action potentials (2-10) in the remaining 43%. 3. The fast EPSP was observed in all cells, and the mean stimulation intensity at its threshold was 53.4 microA. Its amplitude increased with membrane hyperpolarization, and it was associated with a 45.4% decrease in cellular input resistance. The fast EPSP always elicited an action potential at short latencies (3.6-6.4 ms poststimulation). It was reversibly reduced by 6-cyano-7-nitroquinoxaline-2,3- dione (CNQX), a blocker of non-N-methyl-D-aspartate (non-NMDA) excitatory amino acid receptors. 4. The IPSPA was observed in 28/32 cells, and the mean intensity of stimulation was 57.6 microA at its threshold. The mean latency of its peak amplitude was 17.4 ms. The mean equilibrium potential (Erev) was -72.8 mV, and it was associated with a 38.9% decrease in cellular input resistance. IPSPA was blocked by the GABAA antagonist bicuculline. 5. The IPSPB was seen in 29/32 cells, and the mean intensity of stimulation at its threshold was 80.3 microA. Its latency to peak was 130.6 ms, its Erev was -107.6 mV, and it was associated with a small (7.6%) decrease in cellular input resistance. IPSPB was blocked by the GABAB antagonist phaclofen. 6. In 11/32 cells a slower EPSP was also observed. Its mean latency to peak was 53.3 ms, and the mean intensity of stimulation at its threshold was 89.4 microA. In two cells its amplitude decreased with membrane hyperpolarization, and its was associated with a 6.8% increase in cellular input resistance. In 8 of 13 cells showing burst responses, this slow EPSP was present. 7. Both EPSPs and IPSPs were sensitive to repetitive stimulation. The amplitude of the fast EPSP was potentiated during paired-pulse stimulation at interstimulus intervals between 30 and 200 ms and occasionally depressed at intervals of 10-20 ms.(ABSTRACT TRUNCATED AT 400 WORDS)

6-Cyano-7-nitroquinoxaline-2,3-dione↗

PubMed1990

Phaclofen-insensitive presynaptic inhibitory action of (+/-)-baclofen in neonatal rat motoneurones in vitro.

1. Intracellular recordings were made from antidromically identified motoneurones in transverse spinal cord slices from neonatal (12-16 day) rats. 2. Superfusion of (+/-)-baclofen (0.5-50 microM) reduced the excitatory postsynaptic potentials (e.p.s.ps) and inhibitory postsynaptic potentials (i.p.s.ps) evoked by dorsal root or dorsal root entry zone stimulation in a concentration-dependent manner; the calculated EC50 was 2.4 microM. Baclofen in comparable concentrations also reversibly eliminated spontaneously occurring e.p.s.ps and i.p.s.ps. 3. (-)-Baclofen was more effective as compared to baclofen in reducing the synaptic responses, whereas (+)-baclofen at concentrations as high as 50 microM was ineffective. 4. Baclofen (less than 5 microM) attenuated the synaptic responses without causing a significant change of passive membrane properties and depolarizations induced by exogenously applied glutamate. In addition to synaptic depression, baclofen (greater than 5 microM) caused a hyperpolarization associated with decreased membrane resistance in some of the motoneurones; the glutamate responses were also attenuated. 5. Baclofen reversibly depressed the spike after-hyperpolarization of the motoneurones. 6. GABA (1-10 mM) depressed synaptic transmission and depolarized or hyperpolarized motoneurones. While potentiated by the uptake inhibitor nipecotic acid, the synaptic depressant effect of GABA was not antagonized by bicuculline. 7. The synaptic depressant effect of baclofen was neither blocked by GABAA antagonists bicuculline and picrotoxin (10-50 microM) nor by the GABAB antagonist phaclofen (0.1-1 mM). 8. It is suggested that baclofen depresses excitatory and inhibitory transmission in rat motoneurones by primarily a presynaptic mechanism in reducing the liberation of chemical transmitters from nerve endings via a phaclofen-insensitive GABAB receptor.

Animals↗

PubMed2006

Role of protein kinase C in modulation of excitability of CA1 pyramidal neurons in the rat.

Biochemical and in situ hybridization studies demonstrated that the levels of protein kinase C variants were significantly increased in the hippocampus of the experimental models of epilepsy in rats. In addition it has been demonstrated that protein kinase C plays an important role in modulating synaptic transmission in the hippocampus. We examined the effects of activating of protein kinase C on the excitability of CA1 pyramidal neurons and synaptic transmission, using whole-cell current-clamp and extracellular field potential recording techniques. Indolactam V (1 microM) a novel protein kinase C activator, increased the excitability of CA1 neurons acting at both pre- and post-synaptic sites. Indolactam V, acting postsynaptically, significantly reduced the threshold for initiation of action potential from -42+/-3.8 mV to -51+/-3.1 mV and selectively inhibited the slow afterhyperpolarizing potential. Indolactam V also altered the neuronal firing properties in response to prolonged depolarizing pulse by eliminating the spike frequency accommodation. Our data indicate that indolactam V potentiated both amplitudes of Shaffer-collateral stimulation evoked excitatory postsynaptic currents and disynaptically evoked inhibitory evoked postsynaptic currents. However, the potentiation of inhibitory evoked postsynaptic currents amplitudes was not observed after blockade of NMDA and AMPA/kainate currents suggesting it was due to excitatory activity driving inhibitory neurons. The results indicate that the potentiation of pharmacologically isolated excitatory postsynaptic currents (215% of control) and amplitudes of population spikes (290% of control) was due to action of indolactam V presynaptically since the agonist reduced the paired-pulse ratio and the potentiating effect was not blocked by dialyzing the postsynaptic neuron through the recording electrode with a specific protein kinase C inactivator calphostin C. These findings suggest that protein kinase C increases the amplitude of epileptiform activity by causing potentiation of excitatory synaptic transmission, increasing the excitability of postsynaptic neurons and reducing negative feed back provided by slow afterhyperpolarizing potential.

Animals↗

PubMed1997

Excitatory and inhibitory vestibular pathways to the extraocular motor nuclei in goldfish.

Electrophysiological, ultrastructural, and immunohistochemical techniques were utilized to describe the excitatory and inhibitory vestibular innervation of extraocular motor nuclei in the goldfish. In antidromically activated oculomotor motoneurons, electrical stimulation of the intact contralateral vestibular nerve produced short-latency, variable amplitude electrotonic excitatory postsynaptic potentials (EPSPs) at 0.5-0.7 ms followed by chemical EPSPs at 1.0-1.3 ms. Stimulation of the ipsilateral vestibular nerve produced small amplitude membrane hyperpolarizations at a latency of 1.3-1.7 ms in which equilibrium potentials were slightly more negative than resting potentials. The inhibitory postsynaptic potentials (IPSPs) reversed with large amplitudes after the injection of chloride ions suggesting a proximal soma-dendritic location of terminals exhibiting high efficacy inhibitory synaptic conductances. In antidromically identified abducens motoneurons and putative internuclear neurons, electrical stimulation of the contralateral vestibular nerve produced large-amplitude, short-latency electrotonic EPSPs at 0.5 ms followed by chemical depolarizations at 1.2-1.3 ms. Stimulation of the ipsilateral vestibular nerve evoked IPSPs at 1.4 ms that were reversed after injection of current and/or chloride ions. gamma-Aminobutyric acid (GABA) antibodies labeled inhibitory neurons in vestibular subdivisions with axons projecting into the ipsilateral medial longitudinal fasciculus (MLF). Putative GABAergic terminals surrounded oculomotor, but not abducens, motoneurons retrogradely labeled with horseradish peroxidase. Hence the spatial distribution of GABAergic neurons and terminals appears highly similar in the vestibuloocular system of goldfish and mammals. Electron microscopy of motoneurons in the oculomotor and abducens nucleus showed axosomatic and axodendritic synaptic endings containing spheroidal synaptic vesicles establishing chemical, presumed excitatory, synaptic contacts with asymmetric pre- and/or postsynaptic membrane specializations. The majority of contacts with spheroidal vesicles displayed gap junctions in which the chemical and electrotonic synapses were either en face to dissimilar or adjacent to one another on the same soma/dendritic profiles. Another separate set of axosomatic synaptic endings, presumed to be inhibitory, contained pleiomorphic synaptic vesicles with symmetric pre- and/or postsynaptic membrane specializations that never included gap junctions. Excitatory and inhibitory synaptic contacts appeared equal in number but were more sparsely distributed along the soma-dendritic profiles of oculomotor as compared with abducens motoneurons. Collectively these data provide evidence for both disynaptic vestibular inhibition and excitation in all subdivisions of the extraocular motor nuclei suggesting the basic vestibulooculomotor blueprint to be conserved among vertebrates. We propose that unique vestibular neurons, transmitters, pathways, and synaptic arborizations are homologous structural traits that have been essentially preserved throughout vertebrate phylogeny by a shared developmental plan.

Abducens Nerve↗

PubMed2006

The functional nature of synaptic circuitry is altered in area CA3 of the hippocampus in a mouse model of Down's syndrome.

Down's syndrome (DS) is the most common cause of mental retardation, and memory impairments are more severe in DS than in most if not all other causes of mental retardation. The Ts65Dn mouse, a genetic model of DS, exhibits phenotypes of DS, including memory impairments indicative of hippocampal dysfunction. We examined functional synaptic connectivity in area CA3 of the hippocampus of Ts65Dn mice using organotypic slice cultures as a model. We found reductions in multiple measures of synaptic function in both excitatory and inhibitory inputs to pyramidal neurons in CA3 of the Ts65Dn hippocampus. However, associational synaptic connections between pyramidal neurons were more abundant and more likely to be active rather than silent in the Ts65Dn hippocampus. Synaptic potentiation was normal in these associational connections. Decreased overall functional synaptic input onto pyramidal neurons expressed along with the specific hyperconnectivity of associational connections between pyramidal neurons will result in predictable alterations of CA3 network function, which may contribute to the memory impairments seen in DS.

Animals↗

PubMed2006

Catastrophe theory enables moves to be detected towards and away from self-organization: the example of epileptic seizure onset.

Macroscopic systems with many interacting subunits, when driven far from equilibrium, exhibit self-organization, for example when a pathological rhythm appears suddenly in an epileptic patient. Sudden changes occurring while conditions vary smoothly have, in cases of interest, underlying mathematics that are the subject of Thom's catastrophe theory. The assumption made herein that the system's state variables, akin to order parameters, reduce in practice to only one single real variable, ensures that the system derives from a potential function, and warrants recourse to the catastrophe theory. The order parameter is, furthermore, interpreted as a measure of the electropathophysiological activity in the brain, increasing monotonously with the degree of neuronal synchronism. With two neuronal influences, excitatory and inhibitory, as control parameters, the catastrophe is the archetypal cusp. Implementation of catastrophe theory leads to equations showing that fluctuations in a system's dynamics may be utilised for signalling steps precursory to oncoming catastrophes. Pre-seizure dynamics in epileptic patients exhibit steps towards and away from catastrophe; the steps away are interpreted in terms of homeostatic feedback, consequent on changing patterns of neuronal activity. A number of characteristics of epileptic seizures of differing types merely follow from the geometry of the cusp equilibrium surface. In particular, types of seizures are distinguished by their angle of final approach to onset in parameter space. The measurable parameters by which approach to catastrophe is characterized, may be of use in investigations of the organism's plasticity in epileptic patients, and in tests of therapeutic means for preventing seizures. There is no need to resort to a model, in the usual sense of the word, and therefore no differential equation needs to be set up.

Action Potentials↗

PubMed2005

Properties of long-term synaptic plasticity and metaplasticity in organotypic slice cultures of rat hippocampus.

The aim of this study was to investigate whether synaptic plasticity and metaplasticity in slice cultures of the young rat hippocampus were comparable to previously reported synaptic plasticity and metaplasticity in acute adult hippocampal slices. This is relevant since differences do exist between the preparations as a result of age and the ex vivo maintenance. We prepared and maintained slice cultures from 5- to 6-day-old rats according to the porous membrane method. After 12-16 days in vitro, extracellular low-frequency stimulation (LFS) and high-frequency stimulation (HFS) protocols were applied to the Schaffer collaterals, and extracellular field potentials were recorded in area CA1. LFS and HFS induced long-term depression (LTD) and long-term potentiation (LTP), respectively. LTP could be reversed by LFS, as could LTD by HFS 60 min after induction. Plotting the amount of LTD and LTP versus stimulation protocol demonstrated frequency-dependence of the sign and extent of plasticity. Priming activation of group 1 metabotropic glutamate receptors (mGluRs) with DHPG facilitated subsequent LTP, revealing a metaplastic effect similar to that observed in acute slices. Immunohistochemistry for group 1 mGluR subtypes mGluR1alpha and mGluR5 showed both receptors to be present in these cultures. We conclude that synaptic plasticity and mGluR-mediated metaplasticity are largely comparable to those effects found in acute in vitro techniques.

Animals↗