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G A Clark

Publications and source records attributed to G A Clark.

At least 19 recordsLinked to original sources
PubMed2001

Post-light potentiation at type B to A photoreceptor connections in Hermissenda.

We investigated whether the long (approximately 30-s) or short (approximately 3-s) light stimuli that have been used during behavioral training would induce post-light potentiation (PLP) at the type B to A photoreceptor connections of the isolated nervous system of Hermissenda. We found that a single approximately 30-s light step induced PLP at these connections relative to both pre-light baseline and seawater control preparations, as did a series of nine short (approximately 3-s) light steps. In addition, a 30-s step of depolarization-elicited type B cell activity induced potentiation comparable to that induced by a approximately 30-s light step, indicating that light-elicited type B cell activity contributes to the induction of PLP. By contrast, even though a series of short (3-s) light steps induced potentiation, short steps of depolarization-evoked type B cell activity did not. Hence, light-evoked processes other than type B cell depolarization or activity (e.g., perhaps intracellular Ca2+ release) also contribute to the induction of PLP. Further results suggest that these other light-evoked processes interact nonadditively with type B cell activity to generate PLP. Some but not all instances of synaptic potentiation were accompanied by various changes in parameters of type B cell action potentials and afterhyperpolarizing potentials, suggesting diverse underlying mechanisms, including increases in neurotransmitter release. Given that the type A cells have been proposed to polysynaptically excite the motor neurons that drive phototaxis, a light-evoked potentiation of synaptic strength at the inhibitory type B to A photoreceptor connections may play a mechanistic role in light-elicited nonassociative learning.

Adaptation, Physiological↗
PubMed1998

Human monogamy.

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Animals↗
PubMed1998

Synaptic depression at type B to A photoreceptor connections in Hermissenda.

We quantified synaptic depression at the type B to A photoreceptor connections of Hermissenda. Type B cell action potentials were evoked at interstimulus intervals (ISIs) of 0.3, 3 or 30 s and the resulting inhibitory postsynaptic potentials (IPSPs) were recorded in a type A cell. A progressive decline in IPSP amplitude occurred at all three ISIs. Synaptic depression was greater at shorter ISIs, as was the level of recovery 2 min after the stimulus series. The profound level of synaptic depression observed (79.0+/-3.2% at the 0.3 s ISI) implies that synaptic depression is an important control process in the neuronal circuitry that drives phototactic behavior.

Action Potentials↗
PubMed1997

GABA-induced synaptic facilitation at type B to A photoreceptor connections in Hermissenda.

Gamma-aminobutyric acid (GABA) is a prevalent neurotransmitter in both vertebrate and invertebrate systems. Here we report that, in addition to its usual inhibitory actions, GABA induced synaptic facilitation at type B to A photoreceptor connections of the marine mollusk Hermissenda when applied transiently to the isolated nervous system. Synaptic facilitation also occurred in response to mechanical stimulation of the GABAergic hair cells, which are normally activated by rotational unconditioned stimuli during behavioral training of the intact animal. This synaptic facilitation represents a novel form of GABA-induced neuromodulation which may contribute to learning-dependent suppression of phototaxis in Hermissenda.

Action Potentials↗
PubMed1996

Modeling Hermissenda: I. Differential contributions of IA and IC to type-B cell plasticity.

We developed a multicompartmental Hodgkin-Huxley model of the Hermissenda type-B photoreceptor and used it to address the relative contributions of reductions of two K+ currents, IA and IC, to changes in cellular excitability and synaptic strength that occur in these cells after associative learning. We found that reductions of [symbol: see text] C, the peak conductance of IC, substantially increased the firing frequency of the type-B cell during the plateau phase of a simulated light response, whereas reductions of [symbol: see text] A had only a modest contribution to the plateau frequency. This can be understood at least in part by the contributions of these currents to the light-induced (nonspiking) generator potential, the plateau of which was enhanced by [symbol: see text] C reductions, but not by [symbol: see text] A reductions. In contrast, however, reductions of [symbol: see text] A broadened the type-B cell action potential, increased Ca2+ influx, and increased the size of the postsynaptic potential produced in a type-A cell, whereas similar reductions of [symbol: see text] C had only negligible contributions to these measures. These results suggest that reductions of IA and IC play important but different roles in type-B cell plasticity.

Animals↗
PubMed1996

Modeling Hermissenda: II. Effects of variations in type-B cell excitability, synaptic strength, and network architecture.

Because the Hermissenda eye is relatively simple and its cells well characterized, it provides an attractive preparation for detailed computational analysis. To examine the neural mechanisms of learning in this system, we developed multicompartmental models of the type-A and type-B photoreceptors, simulated the eye, and asked three questions: First, how do conductance changes affect cells in a network as compared with those in isolation; second, what are the relative contributions of increases in B-cell excitability and synaptic strength to network output; and third, how do these contributions vary as a function of network architecture? We found that reductions in the type-B cells of two K+ currents, IA and IC, differentially affected the type-B cells themselves, with IC reductions increasing firing rate (excitability) in response to light, and IA reductions increasing quantal output (synaptic strength) onto postsynaptic targets. Increases in either type-B cel excitability or synaptic strength, induced directly or indirectly, each suppressed A-cell photoresponses, and the combined effect of both changes occurring together was greater than either alone. To examine the effects of network architecture, we compared the full network with a simple feedforward B-A pair and intermediate configurations. Compared with a feedforward pair, the complete network exhibited greater A-cell sensitivity to B-cell changes. This was due to many factors, including an increased number of B-cells (which increased B-cell impact on A-cells), A-B feedback inhibition (which slowed both cell types and altered spike timing relationships), and B-B lateral inhibition (which reduced B-cell sensitivity to intrinsic biophysical modifications). These results suggest that an emergent property of the network is an increase both in the rate of information acquisition ("learning") and in the amount of information that can be stored ("memory").

Animals↗
PubMed1996

Differential responses of Aplysia siphon motor neurons and interneurons to tail and mantle stimuli: implications for behavioral response specificity.

1. Tail shock and mantle shock elicit different forms of siphon responses in Aplysia (flaring and backward bending vs. constriction and forward bending, respectively). Moreover, training with these two unconditioned stimuli (USs) in US-alone or classical conditioning paradigms differentially modifies the direction of the response to a siphon tap subsequently presented. As a first step toward addressing neural mechanisms underlying this response specificity, we systematically mapped the central siphon withdrawal circuit to determine which motor neurons and interneurons are differentially engaged by, and potentially modified by, tail and mantle USs. We utilized semi-intact preparations consisting of the intact mantle organs (including the gill and siphon), the tail, and the abdominal and circumesophageal ganglia. USs were delivered either cutaneously through silver wires implanted in the tail and mantle or via suction electrodes to the tail and branchial nerves. 2. We found that one class of central siphon motor neurons, the LFSB cells, was preferentially activated by tail USs, whereas other siphon motor neurons, the LBs cells and RDs cells, were preferentially activated by mantle USs. These motor neurons thus appear to be the final common path for the differential siphon movements to these USs. In addition, because activation of these cells can elicit neuromuscular facilitation and thereby enhance siphon movements, this differential activation may contribute to behavioral response specificity by imposing a specific response bias. 3. L29 interneurons, which both mediate and modulate the siphon withdrawal response, responded preferentially and exhibited synaptic facilitation selectively in response to tail shock USs. In contrast, L34 and the interneuron II network did not show differential activation. Facilitation at L29-LFSB connections following training with tail shock may contribute to tail-directed siphon responses to siphon tap and may thus be an additional mechanism contributing to behavioral response specificity. Possibly, facilitation at other L29 connections could also enhance its modulatory capabilities. 4. The generation of specific response topographies thus appears to involve the coordinate regulation of diverse neuronal elements and multiple mechanisms, which may contribute to different aspects of learning.

Animals↗
PubMed1994

Extrapulmonary beta 2-responses to intravenous salbutamol during the menstrual cycle.

Extrapulmonary beta 2-adrenoceptor mediated responses to salbutamol were evaluated in 9 healthy female subjects during the follicular (day 2-4, Visit 1) and luteal (day 21-23, Visit 2) phases of the menstrual cycle, and were compared with those of 9 age-matched male controls. At each visit, salbutamol was given by intravenous infusion for 30 minutes at a dose of 0.2 mg.kg-1.min-1. Plasma salbutamol concentration and responses in heart rate (HR), finger tremor (Tr), Q-T interval (Q-Tc), serum potassium (K), serum insulin (Ins) and serum glucose (Glu) were measured at baseline and at 10, 20 and 30 minutes after commencing the infusion. Comparisons were made between sexes and between visits for peak responses calculated as percentage change from baseline. Mean plasma salbutamol concentration (ng.ml-1) were not significantly different between males and females on Visit 1: 6.9 (95% CI 6.01, 7.82) vs 7.3 (95% CI 6.4, 8.3), or on Visit 2: 6.9 (95% CI 6.0, 7.8) vs 7.2 (95% CI 6.3, 8.1). On Visit 1, significantly greater responses were demonstrated in females, compared with males for K (as mean difference): 6 (95% CI 1, 11)%, Tr: 17 (95% CI 1, 33)%, Q-Tc: 8 (95% CI 2, 14)% and Ins: 276 (95% CI 71, 481)%. In addition, a significantly greater response was demonstrated in females on Visit 1 compared with males on Visit 2 for HR (as mean difference): 32 (95% CI 1, 63)%, and for Ins: 262 (95% CI 57, 467)%. Thus, despite no difference in plasma salbutamol concentrations, female subjects exhibited greater responsiveness to salbutamol compared with males during the follicular phase of the menstrual cycle. This suggests that in vivo, females have enhanced sensitivity of extrapulmonary beta 2-adrenoceptors.

Adult↗
PubMed1994

Synaptic facilitation at connections of Hermissenda type B photoreceptors.

The enhancement of excitability in type B photoreceptors is an important neural mechanism underlying classically conditioned suppression of phototaxis in the marine mollusk Hermissenda crassicornis. However, the possibility that type B photoreceptors also exhibit synaptic plasticity has not previously been explored. We now report that connections of type B photoreceptors onto type A photoreceptors exhibit synaptic facilitation, and that this facilitation involves the same first messenger (5-HT) and second messenger (protein kinase C) previously implicated in the learning-produced excitability changes. In brief, we found that application of 5-HT dramatically facilitates synaptic potentials evoked by type B cells in type A cell cells, and that this facilitation is blocked by preincubation with staurosporine, a protein kinase inhibitor. Furthermore, activation of protein kinase C also induces synaptic facilitation, whereas activation of the cAMP-dependent protein kinase has no effect. Changes in synaptic strength produced by these manipulations are paralleled by changes in type B cell input resistance (a simple index of cellular excitability), whereas type A cell input resistance is unaffected. These findings indicate a previously unrecognized form of neuronal plasticity in Hermissenda that may contribute importantly to the learned changes in behavior, and thereby highlight general principles of learning-related neuronal plasticity shared by different preparations and species.

Alkaloids↗
PubMed1993

Induction of long-term facilitation in Aplysia sensory neurons by local application of serotonin to remote synapses.

Long-term synaptic facilitation at the connections of Aplysia sensory neurons onto their target cells involves alterations in gene expression. How then are the relevant cellular signals for the induction and expression of long-term synaptic changes conveyed between the nucleus and remote synaptic terminals? We have explored this question using a set of remote, peripheral terminals of siphon sensory cells, which are approximately 3 cm from the sensory cell body in the abdominal ganglion. We found that these remote synapses, like the proximal synapses previously studied in dissociated cell culture, can exhibit long-term facilitation 24 hr after cell-wide serotonin application. Furthermore, serotonin applications restricted to the remote synaptic terminals nevertheless produced long-term facilitation, indicating that signals generated in synaptic regions can trigger the long-term process, perhaps via retrograde signals to the nucleus to modify gene expression, followed by anterograde signals back to the terminal. Serotonin applications restricted to the cell body and proximal synapses of the sensory neuron also produced long-term facilitation at remote synapses, although to a lesser extent, suggesting that long-term facilitation is expressed cell-wide, but that superimposed on this cell-wide facilitation there appears to be a component that is synapse-specific.

Animals↗
PubMed1989

Pharmacokinetics, efficacy and adverse effects of sublingual salbutamol in patients with asthma.

Administration of drugs by the sublingual route provides rapid systemic absorption and avoids first-pass metabolism. The purpose of the present study was to assess the pharmacokinetics, efficacy and adverse effects of standard salbutamol tablets given by this route to patients with asthma. Seven asthmatic patients were given either sublingual salbutamol tablet 2 mg (SL), swallowed tablet 2 mg (O), metered dose inhaler 200 micrograms (MDI) or placebo (PL), in a randomized single-blind cross-over design. Airways responses (FEV1, FVC, PEFR), finger tremor (Tr), heart rate (HR), plasma potassium (K) and plasma salbutamol were measured over a 6 h period following drug administration. There were highly significant changes in FEV1 with MDI, O and SL routes compared with PL, although the response to MDI was greater and more rapid than with O or SL. There were similar findings for FVC and PEFR responses. There were no adverse effects with MDI, whereas both 0 and SL produced significant tremor responses. There were no differences between O and SL for any of the pharmacodynamic parameters. In addition, pharmacokinetic profiles for O and SL were also similar apart from an initial delay in absorption with SL. There were however, no significant differences in any of the pharmacokinetic parameters, between O and SL. This suggest that buccal absorption of salbutamol was negligible, and that systemic absorption occurred after swallowing of the dissolved sublingual tablet. These results show that sublingual administration of salbutamol tablet has no clinical benefit over the oral route.

Administration, Inhalation↗
PubMed1989

Classical conditioning of the Aplysia siphon-withdrawal reflex exhibits response specificity.

The gill- and siphon-withdrawal reflex of Aplysia undergoes classical conditioning of its amplitude and duration when siphon stimulation (the conditioned stimulus, CS) is paired with tail or mantle shock (the unconditioned stimulus, US). This conditioning of a preexisting response exhibits both temporal and stimulus specificities, which can be accounted for by activity-dependent enhancement of presynaptic facilitation of the siphon sensory neurons. To test whether conditioning of the reflex also exhibits response specificity (development of a new type of response to the CS that often resembles the response to the US), we measured the direction of siphon withdrawal in response to siphon stimulation (the CS) with tail or mantle shock as the US. The unlearned response to siphon stimulation is straight contraction, the response to tail shock is backward bending, and the response to mantle shock is forward bending. In the first experiment, we trained different animals with the tail or mantle US paired or unpaired with the CS; in a second experiment, we trained each animal with two CSs, one of which was paired with the US; in a third experiment, we varied US intensity; and in a fourth experiment, we trained each animal with two USs, one of which was paired with the CS. There was a significant, pairing-specific tendency for the direction of the response to the CS to resemble the response to the US after training in each experiment, demonstrating response specificity in conditioning of the withdrawal reflex. This feature of conditioning could in principle be accounted for by an elaboration of activity-dependent facilitation.

Animals↗
PubMed1988

New method for assessing changes in growth and sexual dimorphism in paleoepidemiology.

This paper has three goals. First, traditional methods used for analyzing growth disruption (GD) and sexual dimorphism (SD) in prehistoric skeletal populations are critiqued. Second, a new method, using adult vertebrae, is presented which helps overcome these limitations. Third, this new method is then tested in the Dickson Mounds skeletal population. Between A.D. 950 and 1300 this population underwent a transition from hunting and gathering (PreMississippian: PreMiss.) to maize horticulture (Mississippian: Miss.). Previous research has found a decrease in long bone length in Miss. children, but no difference in adults, or a change in SD. Could this be due to catch-up growth? In the adult skeleton vertebral neural canals (VNCs) size and vertebral body heights (VBHs) can easily be measured. VNCs generally cease growth by early childhood, whereas VBHs grow through young adulthood. This new method offers inference into prehistoric GD and SD previously thought impossible. For example, if VNCs are reduced, but not VBHs, it implies early GD with subsequent catch-up growth. If both VNCs and VBHs are reduced, GD was presumably chronic. Moreover, within this framework, preadult SD can be examined. Results from Dickson show that early GD was followed by catch-up growth. There was a significant change in SD, with females becoming smaller. They had chronic GD. Miss. males had early GD, followed by catch-up growth. Indeed, Miss. males, compared to PreMiss. males, had significantly larger VBHs. Together, these results suggest females lost, but males gained, social status. Thus, vertebral morphometrics may be an invaluable new tool for paleoepidemiologists.

Adolescent↗
PubMed1988

Parallel processing of short-term memory for sensitization in Aplysia.

How is the short-term memory for a single form of learning distributed among the various elements of a neuronal circuit? To answer this question, we examined the short-term memory for sensitization, using the siphon component of the defensive gill- and siphon-withdrawal reflex. We found that the memory for short-term sensitization is represented by at least four sites of circuit modification, each involving a different type of plasticity. These include (1) presynaptic facilitation of the sensory neuron connections onto both interneurons and motorneurons; (2) presynaptic inhibition at the connections of the L30 inhibitory neurons onto the excitatory interneuron L29; (3) posttetanic potentiation of the excitatory connections made by L29 onto a specific subclass of siphon motorneurons, the LFS cells; and (4) an increase in the tonic firing rate of the LFS siphon motor neurons, resulting in neuromuscular facilitation. Each of the heterosynaptic changes seems to involve a common modulatory transmitter and to utilize a common second messenger system. Moreover, each of these sites seems capable of encoding a different component of the short-term memory. Facilitation of the connections of sensory neurons should contribute to the increase in amplitude of the response; the disinhibition of the L29 interneurons and the posttetanic potentiation at L29 synapses should contribute to an increase in the duration of the response; and the increase in tonic firing of the LFS subclass of siphon motor neurons seems capable of contributing both to an increase in response amplitude and to changes in response topography.

Animals↗