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T H Brown

Publications and source records attributed to T H Brown.

At least 73 records · Page 4Linked to original sources
PubMed1986

Differential conditioning of associative synaptic enhancement in hippocampal brain slices.

An electrophysiological stimulation paradigm similar to one that produces Pavlovian conditioning was applied to synaptic inputs to pyramidal neurons of hippocampal brain slices. Persistent synaptic enhancement was induced in one of two weak synaptic inputs by pairing high-frequency electrical stimulation of the weak input with stimulation of a third, stronger input to the same region. Forward (temporally overlapping) but not backward (temporally separate) pairings caused this enhancement. Thus hippocampal synapses in vitro can undergo the conditional and selective type of associative modification that could provide the substrate for some of the mnemonic functions in which the hippocampus is thought to participate.

Animals↗
PubMed1986

Hebbian synapses in hippocampus.

A combination of current- and voltage-clamp techniques applied to hippocampal brain slices was used to evaluate the role of postsynaptic electrogenesis in the induction of associative synaptic enhancement. In accordance with Hebb's postulate for learning, repetitive postsynaptic spiking enabled enhancement in just those synapses that were eligible to change by virtue of concurrent presynaptic activity. However, the essential postsynaptic electrogenic event that controlled the enhancement was shown to involve biophysical processes that were unknown when Hebb formulated his neurophysiological postulate. The demonstrated spatiotemporal specificity of this pseudo-Hebbian conjunctive mechanism can account qualitatively for the known neurophysiological properties of associative long-term potentiation in these synapses, which in turn can explain the "cooperativity" requirement for long-term potentiation.

Animals↗
PubMed1986

Conductance mechanism responsible for long-term potentiation in monosynaptic and isolated excitatory synaptic inputs to hippocampus.

The biophysical mechanisms underlying long-term potentiation (LTP) were investigated in identifiable and monosynaptic excitatory inputs to hippocampal neurons. The results provide the first insights into the conductance changes that are responsible for the expression of LTP. Both current- and voltage-clamp measurements of the mossy fiber synaptic response in pyramidal neurons of region CA3 were made with a single-electrode-clamp system. The excitatory postsynaptic response was pharmacologically isolated by bathing hippocampal slices in saline containing 10 microM picrotoxin, which blocks the synaptic inhibition that normally accompanies the experimentally evoked mossy fiber response. LTP was induced by tetanically stimulating the mossy fiber input for 1 s at 100 Hz. Before and 20 min to 1 h after inducing LTP, we attempted to measure the mean excitatory postsynaptic potential (EPSP) amplitude, intrasomatic current-voltage relationship to a step (RN) or alpha function (AN) current waveform, membrane time constant (tau m), spike threshold (T50), peak excitatory postsynaptic current amplitude (IP), synaptic conductance increase (delta G), and synaptic reversal potential (VR); but adequate assessments of all eight of these were not always obtained for every cell that was studied. The induction of LTP increased the mean (+/- SE) EPSP amplitude form 10.5 +/- 1.4 mV during the control period to 16.8 +/- 2.4 mV after the induction of LTP (n = 14; P less than 0.05). This change was not accompanied by increases in the mean value of RN (63 +/- 11 M omega before and 61 +/- 11 M omega after induction; n = 8; P greater than 0.05); AN, which approximates the effective synaptic input resistance at the soma (10.0 +/- 1.50 M omega before and 10.5 +/- 1.60 M omega after; n = 10; P greater than 0.05); or tau m (22 +/- 2 ms before and 20 +/- 2 ms after; n = 8; P greater than 0.05). There was no significant change in T50, which was also assessed with an alpha function current waveform (1.48 +/- 0.11 nA before and 1.49 +/- 0.10 nA after; n = 6; P greater than 0.05). The mean value of IP increased from 1.1 +/- 0.2 nA during the control period to 1.8 +/- 0.3 nA after inducing LTP (n = 15; P less than 0.05). Similarly, delta G increased from 30 +/- 4 nS before to 47 +/- 4 nS after induction (n = 10; P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Voltage-clamp analysis of synaptic inhibition during long-term potentiation in hippocampus.

The excitatory synaptic response evoked by stimulating the mossy fiber synaptic input to hippocampal CA3 neurons in normally accompanied by concomitant feedforward or recurrent inhibition. The purpose of the present study was to determine whether a decrease in the inhibitory conductance of this mixed synaptic response contributes to the enhanced synaptic efficacy observed during long-term potentiation (LTP). Intracellular recordings were made from CA3 neurons of rat hippocampal brain slices. Current- and voltage-clamp measurements of the mixed excitatory/inhibitory evoked synaptic response were made, using a single-electrode clamp system. Outward and inward rectification were reduced, respectively, by intracellular injection and bath application of Cs+. Biophysical analysis of the evoked synaptic conductance sequence was performed before and 15 min to 1 h after inducing LTP. As expected, measurements made in the early part of the conductance sequence, which represents primarily the monosynaptic excitatory input, demonstrated an increase in the slope conductance during LTP. Measurements made later in the conductance sequence, when the excitatory component appeared to have declined to a negligible value, revealed no decrease in the slope conductance of the inhibitory component of the mixed response. We conclude that a decrease in the conductance associated with the inhibitory component of the mixed synaptic response plays little or no role in the increase in synaptic efficacy observed during LTP of this synaptic system.

Animals↗
PubMed1986

Control theory applied to neural networks illuminates synaptic basis of interictal epileptiform activity.

A brief historical account is presented of the formulation of two hypotheses that have been proposed to explain the mechanisms underlying the paroxysmal depolarizing shift (PDS) in experimental epilepsy. The two hypotheses are called the giant EPSP hypothesis and the endogenous burst hypothesis. The giant EPSP hypothesis states that the PDS (the intracellular correlate of the interictal discharge) is comprised of a larger-than-normal-strength excitatory synaptic input, whereas the endogenous burst hypothesis states that the PDS is an endogenous burst triggered by an excitatory postsynaptic potential of normal strength. Two sets of four experimentally testable predictions, which were derived from these two hypotheses for the PDS, are presented. These predictions describe the expected behavior of the PDS in response to changes in membrane potential and under conditions of voltage clamping. With the advent of single-electrode current- and voltage-clamp techniques and improved intracellular recording conditions, the testing of these predictions has become possible. Experiments are described in which each of the predictions from the two hypotheses were tested. The results strongly support the giant EPSP hypothesis and are not easily reconciled with the endogenous burst hypothesis. Because the PDS is a network-driven event, it is important to understand the properties of the neuronal network responsible for the genesis of the PDS. Others have proposed that there are three necessary conditions for epileptiform activity in any neuronal network: endogenous bursting, disinhibition, and recurrent excitatory synapses. Using control theory as a frame of reference, we argue that it is premature to raise these three phenomena to the level of general theoretical requirements for interictal activity. Insufficient quantitative information exists about the properties of neurons, synapses, and connectivity patterns in any cortical neuronal network to conclude that the three preposed requirements are necessary and sufficient general conditions for epileptiform activity. Because all of the key predictions of the giant EPSP hypothesis have now been experimentally verified, we conclude that the PDS is a large, network-driven EPSP. The current challenge to neurophysiologists is to describe is detail the properties of neurons and synapses in a cortical neuronal network and then to evaluate the relative contributions of network and individual neuronal properties to the expression of interictal epileptiform activity.

Animals↗
PubMed1985

The rapidly growing mycobacteria--Mycobacterium fortuitum and Mycobacterium chelonei.

In summary, rapidly growing mycobacteria, M. fortuitum and M. chelonei, are pathogens of increasing importance which are often hospital-acquired and can infect patients with iatrogenic immunosuppression. They readily grow on routine mycobacterial culture media and must be distinguished from non-pathogenic rapidly growing species and slowly growing mycobacteria. Widely distributed in nature, they are often present in hospital environments, especially in water. Compared to M. tuberculosis they are weak pathogens, and infected patients are not considered contagious. Disease is probably acquired from environmental sources by direct entry of the organisms through traumatized skin or mucous membranes or by aspiration into previously abnormal lungs. They are usually resistant to antituberculous agents but are susceptible to several commonly used antibacterial agents. Treatment generally requires one or more active antibiotics plus adjunctive surgery in many cases. Prevention of nosocomial infection lies in proper disinfection of potentially contaminated medical devices and elimination of contaminated water.

Anti-Bacterial Agents↗
PubMed1985

Quantal mechanism of long-term synaptic potentiation.

Intracellular recordings were used to demonstrate the occurrence and to analyze the microphysiology of long-term synaptic potentiation (LTP) in the crayfish opener neuromuscular synapse. Brief stimulation of the single excitor motor axon enhanced the amplitudes of subsequent postsynaptic potentials for several hours. Three methods of quantal analysis were used to evaluate the mechanism responsible for LTP. The results of all three methods supported predictions of the hypothesis that LTP results from a presynaptic mechanism that increases the average of neurotransmitter quanta evoked by nerve impulses in the excitor axon.

Animals↗
PubMed1985

Failure of chloramphenicol and cefotaxime therapy in Klebsiella meningitis: possible role of antibiotic antagonism.

We have described a patient with Klebsiella pneumoniae meningitis who was treated with cefotaxime and chloramphenicol concomitantly, and whose slow initial resolution and subsequent relapse plus in vitro evidence of antagonism of cefotaxime appear to indicate that chloramphenicol interfered with the activity of the cephalosporin. Thus, concomitant use of chloramphenicol should probably be avoided or used advisedly in adults with gram-negative bacillary meningitis susceptible to a third generation cephalosporin.

Brain Diseases↗
PubMed1985

Neurophysiology and pharmacology of long-term potentiation in the rat sympathetic ganglion.

Brief tetanic stimulation of the preganglionic nerve induced a persistent potentiation of nicotinic synaptic transmission in the rat superior cervical sympathetic ganglion. Quantitative measurements of the post-tetanic increase in synaptic efficacy revealed two distinct time courses. The early, rapidly decaying component, termed post-tetanic potentiation (p.t.p.), had a decay time constant of 2-3 min, as reported elsewhere. The duration of the more persistent component, called long-term potentiation (l.t.p.), was extremely temperature dependent, lasting much longer at 32 degrees C than at 22 degrees C. In half of the experiments performed at 32 degrees C, l.t.p. showed no detectable decay over the course of 1 h or more after a brief tetanic stimulation. Other experiments were conducted at 22 degrees C. The induction of l.t.p. was dependent on the extracellular [Ca2+]. Transient elevation of the extracellular [K+] also produced a long-term enhancement of synaptic efficacy, and this effect was also Ca2+ dependent. The tetani that were effective in inducing l.t.p. (5-20 Hz for 5-20 s) were well within the physiological range of preganglionic activity. The magnitude and time course were related to frequency and duration of stimulation. The occurrence of l.t.p. was restricted to those preganglionic fibres that were tetanically stimulated. This lack of heterosynaptic or generalized effects was demonstrated by splitting the preganglionic nerve into two branches that could be independently tested and conditioned. Physiological activation of muscarinic or nicotinic receptors apparently does not play an essential role in causing ganglionic l.t.p., which is expressed as an enhancement of nicotinic transmission. A muscarinic antagonist (2 microM-atropine) did not block l.t.p. Preganglionic stimulation induced l.t.p. even when a high concentration of a nicotinic antagonist (3 mM-hexamethonium) was present during the tetanic stimulation. Furthermore, bath application of a cholinergic agonist (100-1000 microM-carbachol) could not substitute for tetanic stimulation in provoking l.t.p. Activation of adrenergic receptors also appeared not to play an essential role. Neither a beta-adrenergic antagonist (10 microM-sotolol or 1 microM-propranolol) nor an alpha-adrenergic antagonist (1 microM-phentolamine) had any significant effect on the magnitude or duration of l.t.p. The results indicate that ganglionic l.t.p. is a Ca2+- and temperature-dependent process that can be created independently of the activation of nicotinic, muscarinic or adrenergic receptors.

Action Potentials↗
PubMed1985

A light-guidance system to be used for CT-guided biopsy.

We describe a light-guidance system that uses intersecting helium-neon laser beams to provide precise guidance for biopsy approaches from any direction (including compound angles) during CT-guided biopsy of the chest and abdomen. Interactive software provides visualization of the proposed path, indicates the segment of that path that will pass through each section, and displays the settings for the apparatus.

Biopsy, Needle↗
PubMed1984

The synaptic nature of the paroxysmal depolarizing shift in hippocampal neurons.

It is well known that there are two types of neuronal burst discharges: endogenous and network driven. Frequently, the two types are similar in appearance. But careful analysis has shown them to be quite different mechanistically and to share few common properties. Endogenous bursts are a common feature of certain hippocampal neurons. Application of a convulsant agent to a hippocampal slice, however, results in the appearance of interictal discharges whose intracellular correlate is the paroxysmal depolarizing shift (PDS). In contrast to the normal endogenous burst, the PDS is a network-driven burst. It has been proposed that the underlying depolarization of the PDS constitutes a large, compound, excitatory synaptic potential. In support of this hypothesis, recent voltage clamp experiments have demonstrated that a large synaptic conductance underlies the PDS. In this report we review those experiments and others that have established the synaptic nature of epileptiform activity in the hippocampus.

Animals↗
PubMed1984

Antagonism by chloramphenicol of broad-spectrum beta-lactam antibiotics against Klebsiella pneumoniae.

Chloramphenicol combined with cefotaxime, moxalactam, cefoperazone, aztreonam, or imipenem was tested in vitro against clinical isolates of Klebsiella pneumoniae. By time-kill cultures (killing curves), chloramphenicol interfered with activity of all five beta-lactams. When chloramphenicol was added before the beta-lactams, the action of cefotaxime, moxalactam, or cefoperazone against all isolates was antagonized at all times tested. The action of aztreonam was antagonized against four of six isolates. With imipenem, antagonism occurred against half of the isolates at some time during 24 h when chloramphenicol was added simultaneously, provided that a sufficient inoculum of K. pneumoniae was employed. Generally, less antagonism resulted when chloramphenicol was added after the cephalosporins. Interference of bactericidal activity of three new cephalosporins by chloramphenicol has potential clinical relevance to the therapy of gram-negative bacillary meningitis. The lesser antagonism of aztreonam and imipenem by chloramphenicol is of uncertain clinical relevance but indicates that this in vitro phenomenon may apply to a wide range of beta-lactam antibiotics.

Anti-Bacterial Agents↗
PubMed1983

Associative long-term potentiation in hippocampal slices.

Interactions between two excitatory monosynaptic inputs to hippocampal neurons of the CA1 region were examined in the in vitro slice. By adjusting the strengths of the electrical stimuli delivered to the two input pathways, one was made to generate a weak and the other a strong synaptic response. Simultaneous tetanic stimulation of both input pathways resulted in a subsequent long-term enhanced synaptic efficacy in the weak input under conditions in which the same tetanic stimulation of either input alone failed to have this effect. This form of long-term synaptic potentiation (LTP), known as associative LTP, was shown in some cases to last hours without decrement. The plastic changes were localized within the CA1 region and appear to reside in the pre- or postsynaptic elements of the monosynaptic excitatory input to the pyramidal neurons. The increased synaptic efficacy could not be accounted for by any of several measured postsynaptic passive membrane properties.

Afferent Pathways↗
PubMed1982

Long-term synaptic potentiation in the superior cervical ganglion.

Brief tetanic stimulation of the preganglionic nerves to the superior cervical ganglion enhances the postganglionic response to single preganglionic stimuli for 1 to 3 hours. This long-term potentiation of transmission through the ganglion is apparently not attributable to a persistent muscarinic action of the preganglionic neurotransmitter, acetylcholine, since neither the magnitude nor the time course of the phenomenon is reduced by atropine. The decay of long-term potentiation can be described by a first-order kinetic process with a mean time constant of 80 minutes. We conclude that long-term potentiation, once considered a unique property of the hippocampus, is in fact a more general feature of synaptic function. This form of synaptic memory may significantly influence information processing and control in other regions of the nervous system, including autonomic ganglia.

Animals↗
PubMed1982

Effects of a preventive and suppressive control scheme on the development of thiabendazole-resistance in Ostertagia spp.

Three years after the start of an experiment to assess the merits of thiabendazole (TBZ) treatment of trichostrongylid parasites in weaner sheep, field isolates of Ostertagia spp and Trichostrongylus spp were made from weaner sheep treated under one of three treatment schemes. Treatment frequencies were "nil", "planned" (5 or 6/year) and "regular" (every 3 weeks). In addition an isolate was taken from a group of "tracer" sheep drenched with TBZ every 10 days. Resistance to TBZ was assessed using an in vitro egg hatch assay, pre- and post-treatment faecal egg counts and a controlled anthelmintic efficiency test. Pre- and post-treatment egg counts revealed the presence of TBZ-resistance in field isolates of mixed species. Egg hatch assays indicated a level of resistance for Ostertagia spp which was proportional to the frequency of TBZ treatment. The "planned", "regular" and "tracer" strains of Ostertagia spp had resistance ratios for eggs of 4, 13 and 15 respectively when compared to the "nil" strain. In the anthelmintic efficiency assay treatment with 44 mg kg-1 and 88 mg kg-1 of TBZ removed 82 and 96% respectively of the total Ostertagia burden (adults and larvae) from the "nil" strain and 30 and 75% respectively from the "planned" strain. The same dose rates against the "regular" and "tracer" strains and additional rates of 132 or 176 mg kg-1 against the "tracer" strain failed to reduce the Ostertagia burden significantly. Intestinal Trichostrongylus spp from all isolates were fully susceptible to TBZ at 44 mg kg-1. Levamisole at 7.0 mg kg-1 was highly effective (99% reduction) against the "tracer" strain of Ostertagia.

Animals↗