Biomedical subjects

D K Bilkey

Publications and source records attributed to D K Bilkey.

43 records · Page 3Linked to original sources

PubMed1990

Variation in electrophysiology and morphology of hippocampal CA3 pyramidal cells.

A proportion of pyramidal cells in region CA3 of the mammalian hippocampus generate bursts of action potentials when stimulated with an intracellular injection of depolarizing current. Although a previous study has suggested that burst-type cells are more likely to be located in subregion CA3a than CA3b, it has been unclear if, or how, this burst-type firing was related to cell morphology. In the present study, a sample of pyramidal cells located in subregions CA3a, b and c were recorded intracellularly. Many of these cells were filled with Lucifer yellow, allowing correlation of gross morphology with electrophysiology. Contrary to previous results, it was determined that the proportion of cells which generated bursts did not differ significantly across CA3 subregions. It was found, however, that cells with somata located close to the stratum pyramidale (s.p.)/oriens border ('deep' cells) were more than twice as likely to generate burst-type responses than were cells located closer to stratum radiatum ('shallow' cells). One notable morphological feature of the deep cells was the greater length of the initial portion of their apical dendrite, as measured from soma to primary branching point. This observation is consistent with the hypothesis that burst-type responses are generated or modulated by ion channels on this section of the dendrite.

Action Potentials↗

PubMed1990

The N-methyl-D-aspartate antagonists aminophosphonovalerate and carboxypiperazinephosphonate retard the development and expression of kindled seizures.

To investigate the possible role of N-methyl-D-aspartate (NMDA) receptors in the development and expression of amygdaloid-kindled seizures, rats were either chronically infused with 2-amino-5-phosphonovalerate (APV, 20-40 mM) or pre-injected with carboxypiperazine-phosphonate (CPP, 1-10 mg/kg), both selective NMDA-receptor antagonists, and then kindled from the amygdala. At the higher dose (40 mM), APV blocked the induction of long-term potentiation in the dentate gyrus. APV also retarded clinical seizure development dose-dependently and increased seizure thresholds without affecting afterdischarge (AD) duration. These same doses of APV had only small anticonvulsant effects on established kindled seizures. Although CPP (1-10 mg/kg) had no effect when rats were kindled 45 min after injection it dose-dependently retarded focal and generalization stages at the 150 min injection-kindling interval. Once relieved of drug, animals proceeded to develop stage 5 seizures with shorter duration ADs than saline-control animals. When the previously-kindled, saline groups were crossed to CPP a small depressant effect on seizure expression was observed. These results suggest that NMDA receptors are primarily involved in kindling development rather than in maintaining the kindled state.

2-Amino-5-phosphonovalerate↗

PubMed1990

Time-dependent pro- and anticonvulsant effects of cysteamine on the development and expression of amygdaloid kindled seizures.

The time-dependent pro- and anticonvulsant effects of cysteamine, a depletor of somatostatin, were investigated on the development and expression of amygdaloid kindled seizures. Acute administration of cysteamine (25-400 mg/kg, i.p.) produced a dose-dependent potentiation of kindled seizures when evoked 4 h after the drug. However, the seizures initiated 1 day after drug administration were dose-dependently suppressed. Furthermore, elicitation of seizures 4 h after cysteamine enhanced its anticonvulsant effects at 1 day after the drug, causing a parallel left shift of the dose-response curve. Since it has been reported that somatostatin is released during generalized seizures, the seizures given 4 h after cysteamine may encourage the somatostatin depletion by cysteamine and thereby potentiate its later anticonvulsant effects. The repeated administration of cysteamine (100 mg/kg, i.p.) during kindling development strongly retarded the development of generalized seizures but not the development of focal seizures or of afterdischarges in the amygdala. In contrast to the acute experiments, kindling stimulation given 4 h after each cysteamine treatment did not augment the blocking effect on kindling development. These data indicate that chronic cysteamine treatment has a strong inhibitory effect on the development of amygdaloid kindling.

Amygdala↗

PubMed1988

Myoclonus inducing and seizure modifying effect of cysteamine on cortical and amygdaloid kindled rats.

The effect of the somatostatin depleting substance, cysteamine (100 mg/kg, i.p.), on cortical and amygdaloid kindled seizures was investigated. Cysteamine was tested after the establishment of amygdaloid kindling (AM group) and at two different developmental stages of cortical kindling, namely 'focal-cortical' (FC group) and 'cortico-generalized' seizures (CG group). In control, non-kindled, sham operated animals, cysteamine did not induce any spike activity or myoclonus. However, in all kindled groups clustered spike bursting appeared in the cortex within 5-15 min of the injection. The kindled bursting appeared in the cortex within 5-15 min of the injection. The kindled rats exhibited myoclonic jerks at 10 to 30 min after cysteamine injection, which coincided with the cortical spikes, and continued for about 40 min. In contrast, relatively small amounts of spiking were observed in the amygdala and this did not correlate with the myoclonus. At 4 h after cysteamine injection, the motor seizure and afterdischarge durations of the kindled seizure were prolonged in all kindled groups compared with preinjection levels. However, 24 h later the motor seizure duration and the afterdischarge duration were markedly reduced from the preinjection level in the AM and the CG groups and the tonic seizure component was suppressed in the FC group. This inhibitory effect on seizure activity lasted several days and gradually disappeared. These modifying effects of cysteamine were more marked in cortical kindled, than in amygdaloid kindled animals. The results suggest that the cortex is more sensitive to the effect of cysteamine on kindled seizures involves two phases. The first of these effect of cysteamine on kindled seizures involves two phases.(ABSTRACT TRUNCATED AT 250 WORDS)

Amygdala↗

PubMed1987

Septohippocampal and commissural pathways antagonistically control inhibitory interneurons in the dentate gyrus.

Available evidence suggests that a portion of the septohippocampal pathway may form inhibitory synapses on inhibitory interneurons in the dentate gyrus. In contrast, a portion of the commissural input from the contralateral hilus may form excitatory synapses on inhibitory interneurons. To ascertain whether these pathways synapse onto a common population of interneurons, a series of pulses were applied and their effects on perforant path evoked, granule cell population spikes were measured. The population spike was markedly reduced when the perforant path pulse was preceded by a pulse to the contralateral hilus. This inhibition was markedly reduced, however, when a medial septal pulse was applied either prior to, or within 3 ms after the commissural pulse. The disinhibition was critically dependent on the temporal relationship between the medial septal and commissural pulse, and not on the medial septal-perforant path relationship. This finding suggests that the septohippocampal pathway inhibits the interneurons through which the commissural pathway is able to inhibit granule cells.

Animals↗

PubMed1987

Field potential evidence for long-term potentiation of feed-forward inhibition in the rat dentate gyrus.

Trains of high-frequency stimulation to the perforant path cause (i) long-term potentiation (LTP) of the population excitatory post-synaptic potential (EPSP), (ii) a lasting increase in the population spike, and (iii) a lasting alteration of the relationship between the EPSP and population spike (E-S relationship), consisting of a decreased x-intercept and decreased slope of the linear regression. To compare the thresholds of these changes, we applied a series of trains, increasing in duration from below LTP threshold. The EPSP potentiated with about the same low threshold as the reduction in E-S slope, whereas the reduction in E-S x-intercept required longer trains. In the second experiment, LTP of the EPSP was reduced by concurrent high-frequency stimulation of the commissural input and a lasting reduction of the population spike height was observed. In a third experiment, picrotoxin, an antagonist of gamma-aminobutyric acid (GABA)-mediated inhibition, blocked the decrease in slope of the E-S relationship which normally accompanies LTP. These results imply that perforant path/granule cell LTP is normally accompanied by long-term potentiation of a feed-forward inhibitory pathway which may involve interneurones.

Animals↗

PubMed1985

Medial septal facilitation of hippocampal granule cell activity is mediated by inhibition of inhibitory interneurones.

Rats under barbiturate anaesthesia were implanted with stimulating electrodes in the medial septal nucleus and the medial perforant path. A recording electrode and cannula were implanted in the hilus of the dentate gyrus. Electrodes were positioned so that a conditioning pulse to the medial septum, although eliciting no field potential of its own, facilitated the granule cell population spike evoked by medial perforant path stimulation. In the first experiment, the infusion into the hilus of the GABA antagonist picrotoxin was found to block the facilitation. In a second experiment, it was found that a medial septal conditioning pulse blocked recurrent inhibition of the granule cells, only if it was timed to coincide with their initial activation. We suggest that these effects are mediated through an inhibitory connection from the medial septum onto inhibitory interneurones in the dentate gyrus, and that this connection may utilize the neurotransmitter GABA.

Animals↗