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D K Bilkey

Publications and source records attributed to D K Bilkey.

At least 37 records · Page 2Linked to original sources
PubMed1997

Current source density analysis of the potential evoked in hippocampus by perirhinal cortex stimulation.

Previous anatomical research has demonstrated that the perirhinal cortex (PRC) projects to the dorsal hippocampal CA1 field. We have recently presented data (Liu and Bilkey, Hippocampus 1996; 6:125-135) which suggests that this pathway courses via the lateral perforant path (LPP). In the present study, laminar profiles of the average evoked potentials and current source density (CSD) analysis were used to study the input from the perirhinal cortex to the dorsal hippocampus in the urethane-anaesthetized rat. Stimulation of the lateral perforant path activated a current sink in the stratum lacunosum-moleculare of CA1 and the outer molecular layer of the dentate gyrus with an onset latency of 3.5 ms. Stimulation of the perirhinal cortex produced a very similar sink-source pattern with an onset latency of 4.0 ms. Higher-intensity stimulation of lateral entorhinal cortex also produced a similar pattern with an onset latency of 4.5 ms. Electrolytic lesions of PRC conducted 4-5 days prior to testing resulted in a major decrease (58%) in the amplitude of the LPP-elicited potentials and a corresponding reduction across the whole source-sink pattern. A similar result was observed following ibotenic acid lesions of PRC. In contrast, similar-sized electrolytic lesions of lateral entorhinal cortex produced a much smaller (16%) decrease in potential amplitude and little change in the source-sink pattern. These data provide further support for the hypothesis that perirhinal cortex projects to both the dentate gyrus and CA1 regions of the hippocampus via the lateral perforant path.

Afferent Pathways↗
PubMed1996

Characterization of epileptiform field potentials recorded in the in vitro perirhinal cortex of amygdala-kindled epileptogenesis.

The perirhinal cortex (PRC) has recently been reported that the excitatory role of this area is important for the generation and the propagation of kindled seizures. In the present study, we investigated the extracellular electrophysiological properties of the circuitry which contribute to the propagation of seizures in the PRC, and examined the hypothesis that amygdala-kindling changes the electrophysiological nature of the rat PRC slice in vitro. Field potentials elicited in the PRC had extended duration (> 200 ms, most approximately equal to 1 s) with overlying spike components. The potentials showed strong synchronizing effect governed by an all-or-none rule. Although spontaneous epileptiform discharges that were equivalent in appearance to synaptically-activated field potentials were observed in the PRC of both amygdala-kindled and control rats, the number of slices showing spontaneous activity was significantly larger in the kindled group than in the control group (chi 2-test, P < 0.01). The occurrence of tetanus-induced afterdischarges in kindled rats was significantly higher than in control rats (chi 2-test, P < 0.01). The afterdischarge durations of control slices were generally short and the afterdischarges did not consist of the typical "tonic-clonic' phases. However, the occurrence of the electrographical seizure in the high K+ ACSF were not affected by amygdala-kindling operation. These results indicate that amygdala-kindling lowers the threshold for transsynaptic excitability and enhances the synchronized activity of the PRC induced by episodic proconvulsive manipulations such as tetanus stimulation.

Amygdala↗
PubMed1996

Long-term potentiation in the in vitro perirhinal cortex displays associative properties.

Brief high frequency tetanization trains reliably induced input-specific long-term potentiation (LTP) in slices of rat perirhinal cortex maintained in vitro. Furthermore, associative interactions between inputs were observed following simultaneous tetanization of separate inputs. This associativity may be mediated via NMDA receptors as LTP was blocked in the presence of APV. These results suggest that LTP may underline participation of perirhinal cortex in memory processes.

2-Amino-5-phosphonovalerate↗
PubMed1996

Long-term potentiation in the perirhinal-hippocampal pathway is NMDA dependent.

The putative memory mechanism known as long-term potentiation (LTP) has been described in both NMDA-dependent and non-NMDA-dependent forms. The aim of the present study was to determine which of these forms described the LTP generated between perirhinal cortex (PRC) and hippocampus, two structures which have previously been implicated in learning and memory processes. In urethane-anaesthetized rats, high-frequency stimulation of the PRC induced a significant potentiation of PRC-hippocampal field potentials which was blocked by the NMDA receptor antagonist, MK-801. These data demonstrate that perirhinal-hippocampal LTP is NMDA-dependent and, moreover, that hippocampal-dependent learning which occurs during blockade of the NMDA receptor cannot be attributed to LTP of this pathway.

Animals↗
PubMed1996

Direct connection between perirhinal cortex and hippocampus is a major constituent of the lateral perforant path.

Single-pulse stimulation of the perirhinal cortex (PRC) evoked field responses in the dorsal hippocampal CA1 region in urethane-anesthetized rats. In depth profiles conducted by moving the PRC stimulating electrode, the largest amplitude hippocampal potential was generated when the stimulating electrode was located within the perirhinal region. More dorsal (temporal cortex) or more ventral (lateral entorhinal cortex) stimulating sites elicited minimal hippocampal potentials. The hippocampal response was maintained during 100 Hz stimulation of the PRC, suggesting that it was monosynaptic, and high-frequency stimulation (400 Hz) of the PRC produced a significant potentiation of hippocampal CA1 field potentials (46.73 +/- 4.14%). When the PRC and the lateral perforant path (LPP) were stimulated separately, the depth/amplitude profiles obtained from a roving recording electrode located within the dorsal hippocampus were similar. In order to determine if fibers from PRC project to the hippocampus via the LPP, the PRC-CA1 and LPP-CA1 potentials were recorded prior to and during procaine (20%, 0.5 microliter) blockade of the LPP. A simultaneous loss of both potentials was observed immediately following procaine infusion, while a commissural control potential was unaffected. Both LPP and PRC potentials returned approximately 30-40 min later. Electrolytic lesions of PRC produced a significant decrease in the amplitude of LPP-hippocampal potentials when testing was conducted 4-5 days postlesion. Lesions of lateral entorhinal cortex or temporal cortex did not produce such effects. These data suggest that a direct pathway from perirhinal cortex to the dorsal hippocampal CA1 field can undergo long-term potentiation (LTP) and that this pathway makes a major contribution to the lateral perforant path.

Animals↗
PubMed1995

Lesions of rat perirhinal cortex exacerbate the memory deficit observed following damage to the fimbria-fornix.

Rats that had received bilateral lesions of the perirhinal cortex, fimbria-fornix, combined lesions of both these structures, or sham operations were tested on an object-guided delayed non-match-to-sample task. Perirhinal lesioned and fimbria-fornix lesioned rats were moderately impaired when delay intervals of 30 s or more were introduced between the sample and test phases of the experiment. Animals with combined lesions displayed a considerably greater impairment than animals with lesions of either structure alone. The combined lesioned animals were severely impaired in the initial acquisition of the task and displayed a profound memory deficit at delay intervals of greater than 4 s. These results emphasize the importance of the perirhinal cortex to memory function and suggest that the perirhinal cortex and the hippocampal formation may function interactively in the execution of memory processes.

Animals↗
PubMed1994

The effects of perirhinal cortical lesions on spatial reference memory in the rat.

Rats with bilateral, electrolytic lesions of the perirhinal cortex and sham operated control rats were tested in the Morris water maze, a procedure which has repeatedly been shown to be sensitive to hippocampal and limbic system dysfunction. The results of the present study demonstrate that perirhinal lesioned rats were mildly impaired on this task. The lesioned animals took significantly longer than controls to locate the hidden platform during place navigation acquisition, and had significantly larger heading errors across the entire experimental procedure. In addition, these lesioned animals made fewer platform crossings than control rats during the probe trials. These results suggest that the perirhinal cortex, like the anatomically related entorhinal cortex and hippocampus, may be involved in mnemonic processing.

Animals↗
PubMed1994

Perirhinal cortex lesions in rats disrupt performance in a spatial DNMS task.

Rats with bilateral electrolytic lesions of the perirhinal cortex and sham operated control rats were tested in a spatially guided, delayed non match to sample task. Although perirhinal lesioned animals showed no deficit in acquisition of the task, a performance deficit was observed across longer delay intervals. These results indicate that the perirhinal cortex is a critical component of the network subserving working or declarative memory in the rat.

Animals↗
PubMed1994

Effects of perforant path procaine on hippocampal type 2 rhythmical slow-wave activity (theta) in the urethane-anesthetized rat.

Previous research has suggested that the entorhinal cortex plays a major role in the production of type 1 rhythmical slow-wave activity (RSA) recorded in the hippocampus of the freely moving preparation. In the present experiment we investigated the contribution of the entorhinal cortex to the type 2 fields recorded under urethane anesthesia. Rats had stimulating electrodes and cannulae filled with procaine positioned in the perforant pathway of one or both hemispheres. Recording electrodes were positioned in the dorsal hippocampus of each hemisphere to record perforant path and commissural/associational evoked potentials and RSA fields. Following unilateral procaine blockade, a decrease in RSA amplitude was observed in the stratum oriens and fissure regions of both hemispheres. Concomitant with this change in RSA, there was a loss of perforant path evoked responses, although commissural/associational control potentials remained unaltered. A greater reduction in RSA amplitude was observed following bilateral procaine microinfusion. RSA phase reversal also occurred more dorsally in microelectrode depth profiles conducted through the hippocampus during perforant path inactivation. In current source density analyses performed under baseline conditions, large rhythmic sinks were observed in stratum oriens, in stratum radiatum, and in strata adjacent to the hippocampal fissure. A rhythmic source was often observed in stratum pyramidale. Following perforant path inactivation decreases in the magnitude of the phasic sinks located near the fissure and stratum radiatum were observed. In contrast to the reduction in RSA amplitude observed in the stratum oriens region, the sink in this region and the source in stratum pyramidale remained relatively unaltered. These results demonstrate that the entorhinal region contributes to the production of RSA observed under urethane anesthesia. Furthermore, the CSD and amplitude changes following perforant path inactivation suggest that a substantial portion of RSA recorded in stratum oriens may result from ventrally located RSA dipoles.

Anesthesia↗
PubMed1994

Effects of kainic acid microinfusions on hippocampal type 2 RSA (theta).

This study investigated the effects of bilateral, selective lesions of subfield CA3, produced by intrahippocampal administration of kainic acid, on the generation of hippocampal type 2 RSA. Within 4 weeks of lesioning, animals were anesthetized with urethane and microelectrode depth profiles were performed throughout the dorsal-ventral extent of the hippocampus. In control animals, spontaneous and stimulation-induced RSA was present at the amplitude maxima in stratum oriens of the CA1 and at the level of the hippocampal fissure. Animals that received intrahippocampal microinfusions of kainic acid showed a significant reduction of RSA amplitude at both the stratum oriens and fissure regions. These results suggest that the CA3 subfield may play an important role in the production of type 2 RSA.

Animals↗
PubMed1993

Induction of trypsin-induced hyperexcitability in the rat hippocampal slice is blocked by the N-methyl-D-aspartate receptor antagonist, MK-801.

Bath application of trypsin (0.05%, type I) gave rise to epileptiform activities in CA1 of the rat hippocampal slice. A non-competitive antagonist of N-methyl-D-aspartate (NMDA) receptors, MK-801, blocked the induction of the epileptiform activity, whereas a competitive antagonist, D-APV, showed weak antagonism on the induction of the epileptiform activity. These results may lead us to the understanding of the role of NMDA receptors in the neurotoxic action of trypsin.

2-Amino-5-phosphonovalerate↗
PubMed1993

Stimulation-induced RSA-like field activity in region CA1 of the hippocampal slice: amplitude maxima and topography.

In the present experiment RSA-patterned stimulation was applied to afferents in the CA1 region of the hippocampal slice preparation and depth profiles of the resultant field activity were performed. RSA-patterned stimulation applied to the stratum lacunosum-moleculare region resulted in field activity through the CA1 region with similar morphology, phase, and amplitude profiles to the type 1 RSA profile found in vivo. In contrast, RSA-patterned stimulation applied to the stratum oriens and midstratum radiatum regions did not result in field profiles characteristic of the RSA recorded in vivo. The results of the present study confirm predictions made by previous modelling experiments and CSD analyses performed in the freely moving animal, which suggest that the type 1 RSA profile is primarily the result of distal excitation onto CA1 pyramidal cells.

Afferent Pathways↗
PubMed1992

The infusion of an NMDA antagonist into perirhinal cortex suppresses amygdala-kindled seizures.

The seizure-modulating role of N-methyl-D-aspartate (NMDA) receptors located in several limbic areas was investigated. Amygdala-kindled rats were microinfused with the selective NMDA-receptor antagonist 2-amino-5-phosphonovalerate (APV, 1 microliter, 70 nmol) or artificial cerebrospinal fluid (ACSF) applied through a cannula located in either the amygdala or perirhinal, pyriform or deep prepyriform cortices. APV infused into the stimulation site raised the threshold for seizure generation. Surprisingly, APV infused into perirhinal cortex, but not into other regions, also dramatically suppressed behavioural seizures and afterdischarges (AD) elicited 5 min after the infusion. If stimulus intensities were markedly elevated however, the seizure suppression was overcome. This latter effect was reversible and repeatable, as seizures and AD were reliably reinstated when these animals were stimulated after infusion with ACSF. A similar effect, whereby perirhinal infusions blocked seizure activity, was also demonstrated in an animal kindled from the olfactory bulb and in one kindled from the perforant path. These results suggest that NMDA receptors located in the perirhinal cortex may play a major role in the modulation of AD activity elicited from more distal brain regions. Furthermore, activation of perirhinal cortex may be a critical requirement for the generation of amygdala-stimulated AD in the kindled animal.

2-Amino-5-phosphonovalerate↗
PubMed1992

Induction of immediate-early gene proteins in dentate granule cells and somatostatin interneurons after hippocampal seizures.

The expression of the protein products of the immediate-early genes c-fos, Fos B, Fos-related proteins (FRAs), c-jun, jun B, jun D and krox-24 was investigated in the rat hippocampus at various times after electrically-induced hippocampal seizures. Hippocampal seizures induced all the immediate-early gene proteins in dentate granule cells with differing time-courses. In addition, Krox-24, Fos and Jun D were also induced in somatostatin-containing interneurons throughout the hippocampus and also in a small percentage of parvalbumin-containing interneurons. Thus, hippocampal seizures induce waves of immediate-early gene protein expression in dentate granule cells and a selective expression of krox-24, Fos and Jun D in hippocampal somatostatin interneurons. These results suggest that biochemical and/or morphological changes occurring in dentate granule cells and somatostatin interneurons after seizures may be regulated by immediate-early gene expression, and that these immediate-early gene proteins may be involved in seizure development in the nervous system.

Animals↗
PubMed1991

Kindling-induced persistent alterations in the membrane and synaptic properties of CA1 pyramidal neurons.

Intracellular recordings of CA1 pyramidal cells were performed in in vitro hippocampal slices obtained from control and amygdala- or perforant path-kindled rats. Passive membrane properties did not differ between control and kindled cells. Twenty-three percent of kindled cells, however, displayed burst firing with depolarizing current injection, whereas no control cells produced bursts (P less than 0.01). Two different types of voltage-dependent alteration of depolarizing postsynaptic potentials (PSPs) were also evident in kindled cells. The majority (26/29) of these cells showed a smaller increase (type 1, n = 18), or a sudden decrease (type 2, n = 8), in PSP amplitude with passive membrane hyperpolarization when compared to controls (P less than 0.01). The NMDA antagonist D-APV did not markedly alter the overall slope of the PSP/membrane potential function in either 'type 1' or 'type 2' cells, suggesting that neither behavior was due to a change in the activation characteristics of NMDA receptors. The amplitude of IPSPs was smaller in 'type 1' kindled cells (P less than 0.05) than in controls, however, suggesting that the reduced slope of the PSP/membrane function may be accounted for by a change in inhibition.

Action Potentials↗
PubMed1991

Nifedipine has paradoxical effects on the development of kindling but not on kindled seizures in amygdala-kindled rats.

The effects of nifedipine, an antagonist of voltage-operated calcium channels, on the development of amygdala kindling and on the production of fully kindled seizures, stimulated from the amygdala, were investigated. Rats were treated daily with two doses (5 and 50 mg/kg, i.p.) of nifedipine during the development of kindling. Both doses of nifedipine retarded the development of kindled seizures and 50 mg/kg of nifedipine prolonged the latency to the occurrence of bilateral forelimb clonus. In contrast to these antiepileptogenic effects, however, both doses also increased the duration of afterdischarge. This resulted in a striking increase in the cumulative duration of afterdischarge, required to reach stage 4 and 5 seizures. Contrary to the results of a previous study, 50 mg/kg of nifedipine did not produce any significant effect on fully kindled seizures, regardless of the interval (5 min-24 hr) between injection and stimulation of kindling. These results suggested that although nifedipine inhibited the propagation processes of seizures during development of kindling, it appeared to increase the duration of epileptic activity at the kindling focus.

Action Potentials↗
PubMed1991

Induction of RSA-like oscillations in both the in-vitro and in-vivo hippocampus.

Although the medial septum is generally regarded as the 'pacemaker' of hippocampal Rhythmical Slow Activity (RSA) its precise role has recently been queried, as RSA-like activity can be recorded from in-vitro juvenile hippocampal slices. Here we demonstrate that a critical condition for in-vitro RSA generation in the adult slice is concurrent excitation (provided by bath application of either carbachol or glutamate) and disinhibition (bath application of picrotoxin). Furthermore, under similar conditions of excitation and disinhibition, the in-vivo adult hippocampus is also capable of generating RSA-like oscillations in the absence of septal influences. These findings suggest that, in-vivo, the medial septum may modulate an intrinsically generated hippocampal oscillation through its excitatory and disinhibitory efferents.

Aging↗