Search PubMed⌕ Search

Biomedical subjects

G V Goddard

Publications and source records attributed to G V Goddard.

At least 37 records · Page 2Linked to original sources
PubMed1985

Effects of thyrotropin-releasing hormone on evoked responses and long-term potentiation in dentate gyrus of rat.

Thyrotropin-releasing hormone (TRH), a neuropeptide with multiple neuromodulatory functions, has been receiving examination for clinical relevance in epilepsy. To investigate the neurophysiologic properties of the anticonvulsant action of TRH, its effects on the evoked responses and long-term potentiation (LTP) of the perforant path input to the dentate gyrus were examined in anesthetized rats. Intracerebroventricular microinjected 80 micrograms TRH increased the relationship between the amplitude of the population spike and the slope of the EPSP, and reduced the LTP of the EPSP by approximately 30% compared with saline-injected controls. The TRH, however, slightly increased the amplitude of the population spike. These effects of TRH on LTP were confirmed in a dose-related manner. These results indicate that TRH may have two independent effects in the dentate gyrus, an increase in cellular excitability and a decrease in synaptic plasticity. The latter may be related to the previously reported anticonvulsant effects on kindling.

Animals↗
PubMed1985

Heterosynaptic changes accompany long-term but not short-term potentiation of the perforant path in the anaesthetized rat.

Brief high-frequency trains of electrical stimulation delivered to the perforant path result in long-term potentiation (l.t.p.) of field potentials recorded extracellularly from granule cells of the dentate gyrus. L.t.p. of the population spike is often disproportionately greater than l.t.p. of the population excitatory post-synaptic potential (e.p.s.p.). We have investigated the basis of this effect in rats anaesthetized with sodium pentobarbitone. A series of graded stimuli were given before and after tetanization of the perforant path. From data obtained in this way, we plotted stimulus-response curves, and the relation (E-S curve) between the slope of the population e.p.s.p. (E) and the amplitude of the population spike (S). Curves relating spike onset latency to the slope of the e.p.s.p. were also constructed. Tetanization of the combined medial and lateral components of the perforant path led to long-term changes in the relation between the e.p.s.p. and the population spike. For a given e.p.s.p., the corresponding population spike was of greater amplitude and earlier onset. This E-S potentiation was marked by a shift to the left of the E-S amplitude curve and a downward displacement of the E-S latency curve. Tetanization of the lateral component of the perforant path had two long-term effects on responses evoked by test stimuli to the untetanized medial component: (1) long-term depression of the medial e.p.s.p. and (2) long-term E-S potentiation. The net result of these two heterosynaptically induced effects was to leave unaltered information transfer across medial perforant path-granule cell synapses; for a given test volley the e.p.s.p. was smaller, but because of E-S potentiation the population spike remained relatively unaffected. Short-term potentiation, which has a time course of only a few minutes and is presumed to be mediated by presynaptic mechanisms, was not accompanied by E-S potentiation or by corresponding changes in spike latency. Possible mechanisms of long-term heterosynaptic depression of the e.p.s.p. and of homo- and heterosynaptic E-S potentiation, are discussed. We conclude that although these effects probably reflect a generalized post-synaptic change, this change is unlikely to be a prolonged reduction in the membrane potential of granule cells.

Action Potentials↗
PubMed1984

The effects of disconnection on two phases of kindled frontal-cingulate motor seizures.

The effects of various central nervous system cuts on different aspects of behavioral convulsions were observed in separate groups of rats after kindling in the frontal-cingulate area. Cuts in the corpus callosum lateralized the main aspects of the convulsions whereas coronal and sagittal cuts had little effect. Horizontal cuts beneath the electrode eliminated the phase of the convulsions attributable to the neocortex, even at high-intensity stimulation, but permitted the phase attributable to subcortical seizures. Placement of DC lesions in the lateral thalamus or the red nucleus and brachium conjunctivum abolished the tonic component of the neocortical phase, indicating possible involvement of cerebellar circuitry.

Animals↗
PubMed1984

Adenosine modulation of amygdala kindling.

To test the hypothesis that kindling is restrained by the inhibitory neuromodulator, adenosine, the adenosine uptake blocker, papaverine, or the adenosine antagonist, aminophylline, were injected systemically into rats 20 min before each daily electrical stimulation of the amygdala. The effects on amygdala-triggered seizures of papaverine, adenosine, 2-chloroadenosine, and the adenosine antagonists, isobutylmethylxanthine and caffeine, were also investigated at seizure threshold. Papaverine inhibited kindling, whereas aminophylline accelerated kindling. The adenosine agonists had anticonvulsant effects on seizures, and the antagonists had proconvulsant effects which involved, primarily, the lengthening of afterdischarge duration. Aminophylline injected repeatedly, in the absence of electrical stimulation, induced seizures. These results support the hypothesis that adenosine can modulate kindling and affect the seizure process.

2-Chloroadenosine↗
PubMed1983

Commissural inhibition and facilitation of granule cell discharge in fascia dentata.

Stimulation of the contralateral hippocampus in the hilar region had a marked effect on granule cell excitability in the fascia dentata. The primary effect was to block the population spike that otherwise occurred in response to perforant path stimulation. In contrast, the size the excitatory post-synaptic potential component of the perforant path-evoked field potential was only slightly reduced. The population spike diminution began at short latency (3.5 msec), beginning at about 1.0 msec after the onset of the slow component of the potential evoked by the contralateral stimulus. The completeness and duration of this population spike diminution depended on the contralateral stimulus intensity. The maximum duration was less than 40 msec in unanesthetized rats and more than 100 msec in rats under pentobarbital anaesthesia. Bicuculline did not diminish the field potential evoked by the contralateral stimulus but it did prevent the stimulus from blocking the perforant path population spike and, instead, permitted a weak facilitation of the population spike. The normal reduction of the population spike was not mediated by recurrent inhibition, secondary to granule cell activation, since it occurred whether or not the granule cells were inhibited at the time of contralateral stimulation. These results imply that the initial main effect on fascia dentata granule cells of activity in the contralateral hilus is a gamma-aminobutyric-acid-mediated inhibition. This effect most probably involves commissural excitation of local inhibitory interneurons. The direct excitatory action of commissural fibers on granule cells, by comparison, is very weak.

Anesthesia, General↗
PubMed1983

Reduction of long-term potentiation in the dentate gyrus of the rat following selective depletion of monoamines.

1. Brief, high-frequency stimulation of the perforant path results in a long-term potentiation (l.t.p.) of the field response evoked in the dentate gyrus by single shocks to the perforant path. We have compared the magnitude and duration of l.t.p. in normal, anaesthetized rats with animals depleted of noradrenaline (NA), 5-hydroxytryptamine (5-HT), or both. 2. All animals were exposed to an identical sequence of eight high-frequency trains of increasing intensity given over a period of 140 min to the perforant path of one hemisphere. The potential evoked by test shocks to the perforant path was monitored in both hemispheres throughout this period and for a further 96 min after the last train. 3. Plots of the mean potentiation of the population e.p.s.p. as a function of time were computed for all animals in each group. L.t.p. in the NA-depleted group was about 50% of that in the non-depleted control group throughout the course of the experiment. L.t.p. in the 5-HT-depleted group was more severely affected; mean potentiation did not exceed 30% of that in the control group at any time. 4. The duration of l.t.p. was unaffected by NA depletion and reduced by 5-HT depletion. 5. The threshold for the intensity of high-frequency current pulses necessary to elicit l.t.p. was unaffected by NA depletion and raised by 5-HT depletion. 6. Short-term potentiation of the population e.p.s.p. was unaffected by either NA depletion or 5-HT depletion. 7. The effect of monoamine depletion on granule cell excitability was investigated. 5-HT depletion, but not NA depletion, induced an increase in the excitability of the granule cell population, in the sense that a population e.p.s.p. of a given size was associated with a larger population spike. 8. Long-term potentiation of granule cell excitability was not affected by NA depletion, but was reduced by 5-HT depletion. 9. These results show that monoamines can modulate long-term changes in synaptic function in the dentate gyrus, and suggest that 5-HT is more potent in this respect than NA.

Action Potentials↗
PubMed1982

Septal modulation of the population spike in the fascia dentata produced by perforant path stimulation in the rat.

Electrical stimulation of the perforant path, which originates in the entorhinal cortex, produces a characteristic excitatory postsynaptic field potential (extracellular EPSP) which can be recorded in the fascia dentata. This evoked response may include a population spike, if stimulation is sufficient. In the anaesthetized rat, stimulation of the medial septum, when paired with perforant path stimulation, was found to augment the population spike component of the evoked field potential. Stimulation of the septum alone produced no apparent field potential. The augmentation effect was found to have a rapid onset (4 ms), which is sufficient for the participation of interneurons, and a relatively long time course (150 ms). Presynaptic mechanisms of facilitation were ruled out as there was no concurrent alteration of the extracellular EPSP. A change in population spike threshold, compatible with a postsynaptic mechanism, was observed and some possible models of action discussed. Augmentation survived depletion of hippocampal norepinephrine caused by injections of 6-hydroxydopamine into the dorsal noradrenergic bundle, indicating that the facilitation was not due to an activation of the ascending noradrenergic fibres of passage originating from the locus coeruleus. The cholinergic septo-hippocampal pathway was ruled out as a likely candidate for the modulation as the augmentation survived injections of the muscarinic antagonists atropine and scopolamine and the nicotinic antagonists tubocurarine and dihydro-beta-erythroidine. A relationship between the septal modulation and hippocampal theta was suggested.

Animals↗
PubMed1982

Inhibitory modulation of long-term potentiation: evidence for a postsynaptic locus of control.

Long-term potentiation (LTP) of the excitatory synapses of the perforant path onto the granule cells of the fascia dentata was prevented, or greatly reduced in amount, by stimulation of the contralateral hilus, a source of the commissural afferents and an indirect source of granule cell inhibition. The LTP was reduced only when the onset of contralateral stimulation fell within 50 ms before and 1 ms after the onset of the perforant path conditioning train. Over this time interval, the ability of the volley from the contralateral hilus to block granule cell discharge (population spike) caused by the perforant path conditioning train varied, but not with a time course corresponding to the reduction of LTP. Although trains of impulses applied at high frequency (3-8 pulses at 400 Hz) were often able to block the perforant path LTP completely, single shocks strong enough to block the perforant path population spike were not sufficient to reduce LTP. The results support Marr's proposal that local inhibitory networks may set the threshold for producing long-term synaptic modification. They do not support Hebb's nor Uttley's proposal since the long-term synaptic modification did not depend on either the occurrence or the absence of a postsynaptic action potential.U

Anesthesia, General↗
PubMed1978

Synaptic enhancement in fascia dentata: cooperativity among coactive afferents.

Evidence is presented that long-lasting enhancement of perforant path synapses following high-frequency activity is a cooperative process requiring coactivity of a considerable number of fibers. This was demonstrated in two ways: (1) A threshold stimulus intensity during high-frequency stimulation was required before any enhancement was observed. This threshold was considerably above the stimulus threshold for observing a minimal synaptic response in the fascia dentata. Above the enhancement threshold, the amount of enhancement increased as the intensity of high-frequency stimulation increased. (2) Concurrent high-frequency activation of fibres of the medial and lateral perforant path produced enhancement at intensities where identical but independent stimulation of the two pathways either failed or was less effective. Discharge of the granule cells during the high-frequency stimulation was independently manipulated and found not to be physically coupled to the enhancement generating mechanism.

Afferent Pathways↗
PubMed1977

Circadian rhythm of synaptic excitability in rat and monkey central nervous system.

Synaptic responses in hippocampal granule cells to stimulation of their afferent fibers from the entorhinal cortex fluctuate with a 24-hour period. The phase of this cycle for rats and monkeys depends on whether the animal is naturally nocturnal or diurnal. In a rat blinded by enucleation, the rhythm persists but drifts out of phase with the rhythm of sighted controls.

Action Potentials↗
PubMed1975

Long-term potentiation of the perforant path-granule cell synapse in the rat hippocampus.

When the entorhinal cortex is electrically stimulated, a monosynaptic evoked potential is produced in the ipsilateral hippocampus. Twenty-four hours after a 120-pulse stimulation train, the response to a single test pulse was found to be increased. Stimulation trains presented at a rate of 1/day had a cumulative effect on both the population EPSP and spike components of the evoked potential, and the potentiation so produced lasted at least 12 days. In a few cases, retested 2 months after the last stimulation train, the population EPSP was found to be still highly potentiated while the population spike had declined to initial levels. The most reliable results and largest potentiation were obtained with diphasic stimulation trains of 10 Hz or greater, though some changes were observed even with very low frequencies (0.2 Hz). The results imply that the efficiency of synaptic transmission in the perforant path-granule cell synapse can be modified.

Animals↗
PubMed1975

Does the engram of kindling model the engram of normal long term memory?

The kindling effect is a relatively permanent alteration in brain function which results from repeated electrical or chemical stimulation and culminates in the appearance of electrographic and behavioral convulsions whenever the original stimulus is reapplied. The effect results from tetanic activation in the anterior cortex, limbic system or associated areas of the adult mammalian brain, and the lasting alterations are transynaptic and quite widespread. They are based in part on synaptic facilitation, and they are accompanied by specific alterations in normal behavior. In these and other respects, kindling is analogous to normal learning. It is possible that the stored component (engram) of kindling involves the same physiological mechanism as the engram of normal long term memory. Morphological study of identified synapses has not provided conclusive evidence for an anatomical substrate of kindling, but physiological experiments demonstrate a lasting potentiation of the excitatory post-synaptic potential.

Amygdala↗
PubMed1970

Epileptic focus location: spectral analysis method.

A spectral analysis technique for locating the site of an epileptic focus in the cat brain with the use of multielectrode data, obtained during a generalized seizure, is described. The data, indicating widespread appearance of epileptic activity, does not lend itself to conclusive analysis by conventional means. Three channels of data are examined at a time. One channel is said to drive the other channels if the first channel explains or accounts for the linear relation between the other two over a frequency interval corresponding to the interval of greatest energy concentration. The method of analysis involves computation of the coherence and partial coherence between data from all electrode pairs.

Animals↗