Biomedical subjects

H J Faulkner

Publications and source records attributed to H J Faulkner.

13 recordsLinked to original sources

PubMed2001

Self-organized synaptic plasticity contributes to the shaping of gamma and beta oscillations in vitro.

gamma (30-70 Hz) followed by beta (10-30 Hz) oscillations are evoked in humans by sensory stimuli and may be involved in working memory. Phenomenologically similar gamma-->beta oscillations can be evoked in hippocampal slices by strong two-site tetanic stimulation. Weaker stimulation leads only to two-site synchronized gamma. In vitro oscillations have memory-like features: (1) EPSPs increase during gamma-->beta; (2) after a strong one-site stimulus, two-site stimulation produces desynchronized gamma; and (3) a single synchronized gamma-->beta epoch allows a subsequent weak stimulus to induce synchronized gamma-->beta. Features 2 and 3 last >50 min and so are unlikely to be caused by presynaptic effects. A previous model replicated the gamma-->beta transition when it was assumed that K(+) conductance(s) increases and there is an ad hoc increase in pyramidal EPSCs. Here, we have refined the model, so that both pyramidal-->pyramidal and pyramidal-->interneuron synapses are modifiable. This model, in a self-organized way, replicates the gamma-->beta transition, along with features 1 and 2 above. Feature 3 is replicated if learning rates, or the time course of K(+) current block, are graded with stimulus intensity. Synaptic plasticity allows simulated oscillations to synchronize between sites separated by axon conduction delays over 10 msec. Our data suggest that one function of gamma oscillations is to permit synaptic plasticity, which is then expressed in the form of beta oscillations. We propose that the period of gamma oscillations, approximately 25 msec, is "designed" to match the time course of [Ca(2+)](i) fluctuations in dendrites, thus facilitating learning.

Analgesics, Opioid↗

PubMed2001

Evidence for a common binding cavity for three general anesthetics within the GABAA receptor.

The GABA(A) receptor is an important target for a variety of general anesthetics (Franks and Lieb, 1994) and for benzodiazepines such as diazepam. Specific point mutations in the GABA(A) receptor selectively abolish regulation by benzodiazepines (Rudolph et al., 1999; McKernan et al., 2000) and by anesthetic ethers (Mihic et al., 1997; Krasowski et al., 1998; Koltchine et al., 1999), suggesting the existence of discrete binding sites on the GABA(A) receptor for these drugs. Using anesthetics of different molecular size (isoflurane > halothane > chloroform) together with complementary mutagenesis of specific amino acid side chains, we estimate the volume of a proposed anesthetic binding site as between 250 and 370 A(3). The results of the "cutoff" analysis suggest a common site of action for the anesthetics isoflurane, halothane, and chloroform on the GABA(A) receptor. Moreover, the data support a crucial role for Leu232, Ser270, and Ala291 in the alpha subunit in defining the boundaries of an amphipathic cavity, which can accommodate a variety of small general anesthetic molecules.

Anesthetics↗

PubMed2001

Poor reading comprehension despite fast word decoding in children with hydrocephalus.

Children with hydrocephalus decode words better than they understand what they read. We tested whether children with hydrocephalus (from myelomeningocele or aqueduct stenosis) (1) decode words slowly, (2) use decoding processes similar to those of neurologically intact peers, and (3) comprehend poorly to the extent that they are slow decoders. We compared speed of word decoding in 33 children with hydrocephalus and 33 controls matched on a pairwise basis for age, grade, and word decoding accuracy. The children with hydrocephalus were as fast as controls in reading words, but, unlike controls, they did not demonstrate an effect of spelling-sound regularity. Further, decoding speed did not contribute to reading comprehension beyond word decoding accuracy. The reading comprehension deficits of good decoders with hydrocephalus are not related to early-stage processing deficits in word recognition speed. Likely origins of comprehension failure in this group are discussed.

Adolescent↗

PubMed2000

Pathway-specific habituation of induced gamma oscillations in the hippocampal slice.

Brief tetanic stimulation (eight pulses at 100 Hz) of afferent fibers innervating area CA1 of the hippocampus produce gamma oscillations. When delivered every minute the oscillation habituated markedly after the first stimulus. This habituation could be transiently reversed by stimulating a different pathway to the recorded area. Gamma oscillation-induced beta frequency oscillations were only seen in response to the first (novel) stimulus and the gamma oscillation itself was markedly attenuated by on-going, non-oscillogenic, synaptic activity. The NMDA receptor antagonist ketamine abolished the response to novel stimuli but left the habituated response relatively unaffected. The pattern of habituation parallelled that seen for sensory induced gamma and beta oscillations in the clinical EEG.

Anesthetics, Dissociative↗

PubMed2000

Neuronal fast oscillations as a target site for psychoactive drugs.

Neuronal oscillations within the electroencephalogram beta and gamma bands (15-80 Hz) are associated with intense mental activity and cognitive function in general. Specifically, recent advances have implicated gamma oscillations in the processing of sensory stimuli and demonstrated that synchronous gamma oscillations, appearing concurrently in spatially separate brain regions, can induce beta activity. beta activity generated in this manner represents established synchronous communication between brain regions and is thought to represent a neuronal network correlate of the "binding phenomenon" in cognitive theory. This review will outline the mechanisms of generation of these oscillations at the cellular and network level, and will highlight the effects of drugs that may modify these mechanisms. Possible modification of fast oscillations by disease processes and clinical intervention are discussed.

Animals↗

PubMed1999

On the mechanism of the gamma --> beta frequency shift in neuronal oscillations induced in rat hippocampal slices by tetanic stimulation.

Tetanic stimulation of the CA1 region of rat hippocampal slices can induce gamma frequency population oscillations (30-100 Hz) after a latency of 50-150 msec that are synchronized to within 1-2 msec when simultaneous stimuli are delivered to two sites 2 mm or more apart. When tetanic stimuli, twice-threshold for eliciting gamma oscillations, are used, new phenomena occur. (1) After a period of gamma, there is a switch to beta frequencies (10-25 Hz); (2) during the switch, pyramidal cell spike afterhyperpolarizations (AHPs) increase and rhythmic EPSPs occur in pyramidal cells; and (3) after an episode of single-site, twice-threshold-induced gamma/beta oscillations, simultaneous two-site threshold stimuli induce gamma oscillations that are locally synchronized, but no longer are capable of long-range synchrony. We studied the cellular mechanisms of the gamma/beta switch with electrophysiological techniques and computer simulations. Our model predicts that the observed increases in both pyramidal cell AHPs and in pyramidal/pyramidal cell EPSPs are necessary and sufficient for the beta switch to occur. Firing patterns generated by the model, both for pyramidal cells and for interneurons, resemble experimental records. A one-site twice-threshold stimulus might lead to an inability of the two sites to synchronize at gamma frequencies, after subsequent two-site stimulation, via this mechanism. If depression is induced at synapses coupling pyramidal cells at one site to interneurons at the other site, then two-site stimulation cannot produce interneuron doublets; hence, as shown previously, the two sites will be unable to synchronize. This mechanism works in simulations, and we provide experimental evidence that synaptic depression and loss of doublets occur after a sufficiently strong local tetanus to one site. We suggest that long-range excitatory connections onto interneurons determine whether different pyramidal cell "assemblies" can synchronize at gamma frequencies, whereas excitatory connections onto pyramidal cells determine whether such assemblies can synchronize at beta frequencies.

Animals↗

PubMed1999

Anaesthetic/amnesic agents disrupt beta frequency oscillations associated with potentiation of excitatory synaptic potentials in the rat hippocampal slice.

1. Anaesthetic agents produce disruption in cognitive function typified by reductions in sensory perception and memory formation. Oscillations within the EEG gamma and beta bands have been linked to sensory perception and memory and have been shown to be modified by anaesthetic agents. 2. Synchronous gamma oscillations generated by brief tetanic stimulation in two regions of hippocampal area CA1 in slices in vitro were seen to potentiate excitatory synaptic communication between the areas. This synaptic potentiation, was seen to contribute to a transition from gamma frequency (30 - 70 Hz) to beta frequency (12 - 30 Hz) oscillations. 3. Four drugs having anaesthetic/hypnotic and amnesic properties were tested on this synchronous gamma-induced beta oscillation. Thiopental 10 - 200 microM, Diazepam 0.05 - 1.0 microM, Morphine 10 - 200 microM, and Ketamine 10 - 200 microM were all added to the bathing medium. Each drug markedly disrupted the formation of beta oscillations in a manner consistent with their primary modes of action. Thiopental and morphine disrupted synchrony of gamma oscillations and prevented potentiation of recurrent excitatory potentials measured in stratum oriens (fEPSPs). Neither diazepam, nor ketamine produced such marked changes in synchrony at gamma frequencies or reduction in potentiation of fEPSPs. However, each disrupted expression of subsequent beta oscillation via changes in the magnitude of inhibitory network gamma oscillations and the duration and magnitude of tetanus-induced depolarization respectively. 4. The degree of disruption of fEPSP potentiation correlated quantitatively with the degree of disruption in synchrony between sites during gamma oscillations. The data indicate that synchronous gamma-induced beta oscillations represent a mode of expression of excitatory synaptic potentiation in the hippocampus, and that anaesthetic/amnesic agents can disrupt this process markedly.

Anesthetics↗

PubMed1999

Fluent and nonfluent forms of transfer in reading: words and their message.

In two experiments, we examined transfer to the reading of a normal text from a prior reading of that intact text or from a prior reading of a scrambled word version of the passage. In Experiment 1, we studied good and poor readers in Grade 4; in Experiment 2, high- and low-ability undergraduate readers. Good readers at both ages showed rereading benefits only when the prior reading was of the intact text, with no reliable benefit from experience with words only. The poorer readers showed reliable rereading benefits even when only the words, in a scrambled order, were read on the first encounter. The results are discussed in terms of two forms of transfer nonfluent reading transfer when attention must be focused on word recognition, and fluent rereading transfer when word recognition is skilled so that attention can be focused on text processing.

Adult↗

PubMed1998

Gamma frequency oscillations gate temporally coded afferent inputs in the rat hippocampal slice.

Gamma (25-60 Hz) oscillations are associated with cognitive processing in the cortex. They can be generated by excitation of populations of mutually inhibitory, interconnected interneurons. Such oscillations can entrain the firing patterns of excitatory projection neurons and have been shown both to facilitate the synchronization of spatially separate populations of neurons and mediate changes in synaptic strength that alter the ability of populations to synchronize. Here we demonstrate that gamma oscillations also act as a powerfully selective gate for trains of afferent inputs to an oscillating area, based on the 'precise timing of inputs' as opposed to their absolute magnitude or frequency.

Action Potentials↗

PubMed1998

Morphine disrupts long-range synchrony of gamma oscillations in hippocampal slices.

Oscillations in neuronal population activity within the gamma frequency band (>25 Hz) have been correlated with cognition: Gamma oscillations could bind together features of a sensory stimulus by generating synchrony between discrete cortical areas [Eckhorn, R., Bauer, R., Jordan, W., Brosch, M., Kruse, W., Munk, M. & Reitboeck, H. J. (1989) Biol. Cybern. 60, 121-130; Singer, W. & Gray, C. M. (1995) Annu. Rev. Neurosci. 18, 555-556]. Herein we demonstrate that morphine and beta-endorphin disrupt this long-range synchrony of gamma oscillations while leaving the synchrony of local oscillations relatively intact. The effect is caused by a decrease in type A gamma-aminobutyric acid receptor-mediated inhibition of both excitatory pyramidal cells and inhibitory interneurons. The effects of morphine on gamma oscillations were blocked by mu-opioid receptor antagonists but not by antagonists of delta or kappa receptors. Morphine also produced burst firing in interneurons, because synaptic excitation from pyramidal cells was no longer balanced by synchronous inhibitory postsynaptic potentials. The loss of synchrony of gamma oscillations induced by morphine may constitute one mechanism involved in producing the cognitive deficits that this drug causes clinically.

Analgesics, Opioid↗

PubMed1998

Disruption of synchronous gamma oscillations in the rat hippocampal slice: a common mechanism of anaesthetic drug action.

1. At the molecular level much progress has been made towards elucidating the mechanisms of action of general and dissociative anaesthetics. However, little is known about how these molecular actions may lead to disruption of cognitive function. 2. A promising physiological correlate of cognitive function is the ability of spatially separate areas of the brain to synchronize firing patterns via mutual inhibitory, gamma-frequency (20-80 Hz) electrical oscillations. Here we examine the effects of five different anaesthetic/hypnotic agents with different primary mechanisms of action on these oscillations in the hippocampus. 3. Gamma oscillations were elicited simultaneously at two sites at either end of area CAI by tetanic stimulation. Such oscillations are synchronous between these areas even when separated by up to c. 4 mm in control conditions. 4. Agents which act directly on GABA(A) receptor-mediated inhibition had different effects on synchronous gamma oscillations. Thiopental (10-200 microm) markedly disrupted the oscillation and resulting synchrony whereas the benzodiazepines diazepam and temazepam (0.05-1.0 microM) had little effect. 5. The opiate morphine (10-200 microM) and dissociative agent ketamine (10-100 microM) had a different profile of effects on gamma oscillations. However, as with thiopental, both agents markedly disrupted between site synchrony. These three agents demonstrated this effect at aqueous concentrations relevant to anaesthetic ED50. 6. Using the hippocampus as a model neuronal network we propose that, despite differing primary mechanisms of action, anaesthetics may disrupt cognitive function by interfering with the mechanism of generation of synchronous firing patterns between spatially separate areas of the brain.

Anesthetics↗

PubMed1997

Recurrent excitatory postsynaptic potentials induced by synchronized fast cortical oscillations.

Gamma frequency (about 20-70 Hz) oscillations occur during novel sensory stimulation, with tight synchrony over distances of at least 7 mm. Synchronization in the visual system has been proposed to reflect coactivation of different parts of the visual field by a single spatially extended object. We have shown that intracortical mechanisms, including spike doublet firing by interneurons, can account for tight long-range synchrony. Here we show that synchronous gamma oscillations in two sites also can cause long-lasting (>1 hr) potentiation of recurrent excitatory synapses. Synchronous oscillations lasting >400 ms in hippocampal area CA1 are associated with an increase in both excitatory postsynaptic potential (EPSP) amplitude and action potential afterhyperpolarization size. The resulting EPSPs stabilize and synchronize a prolonged beta frequency (about 10-25 Hz) oscillation. The changes in EPSP size are not expressed during non-oscillatory behavior but reappear during subsequent gamma-oscillatory events. We propose that oscillation-induced EPSPs serve as a substrate for memory, whose expression either enhances or blocks synchronization of spatially separated sites. This phenomenon thus provides a dynamical mechanism for storage and retrieval of stimulus-specific neuronal assemblies.

Animals↗

PubMed1994

How text difficulty and reader skill interact to produce differential reliance on word and content overlap in reading transfer.

Four experiments examined the factors that influence across-text transfer for children. Transfer was indicated by increases in the reading speed and accuracy of a second text following reading of different first texts. The first texts were related to the second by overlap in words only, in content only, in words and content, or in neither words nor content. Results indicated that the extent to which readers benefited from word or content overlap depended on the interaction of reader skill with text difficulty. Children who read texts that were easy for them showed transfer only when a pair of stories shared content. However, when children read stories that were difficult for them, they also showed transfer when words alone were shared by a pair of stories. The results are discussed in terms of how easy and difficult texts are represented in memory and retrieved to produce transfer.

Child↗