Group I, II, and III mGluR compounds affect rhythm generation in the gastric circuit of the crustacean stomatogastric ganglion.

We have studied the effects of group I, II, and III metabotropic glutamate receptor (mGluR) agonists on rhythm generation by the gastric circuit of the stomatogastric ganglion (STG) of the Caribbean spiny lobster Panulirus argus. All mGluR agonists and some antagonists we tested in this study had clear and distinct effects on gastric rhythm generation when superfused over combined oscillating or blocked silent STG preparations. A consistent difference between group I agonists and group II and III agonists was that group I agonists acted excitatory. The group I-specific agonists L-quisqualic acid and (S)-3,5-dihydroxyphenylglycine, as well as the nonspecific agonist (1S,3R)-1-aminocyclopentane-1, 3-dicarboxylic acid accelerated ongoing rhythms and could induce gastric rhythms in silent preparations. The group II agonist (2S,1'S, 2'S)-2-(carboxycyclopropyl)glycine (L-CCG-I) and the group III agonist L(+)-2-amino-4-phosphonobutyric acid (L-AP4) slowed down or completely blocked ongoing gastric rhythms and were without detectable effect on silent preparations. The action of L-CCG-I was blocked partially by the group-II-specific antagonist, (RS)-1-amino-5-phosphonoindan-1-carboxylic acid [(RS)APICA], and the group-III-specific antagonist (RS)-alpha-methyl-4-phosphonophenylglycine completely blocked the action of L-AP4. Besides its antagonistic action, the group-II-specific antagonist (RS)APICA had a remarkably strong apparent inverse agonist action when applied alone on oscillating preparations. The action of all drugs was dose dependent and reversible, although recovery was not always complete. In our experiments, the effects of none of the mGluR-specific agonists were antagonized or amplified by the N-methyl-D-aspartate (NMDA)-receptor-specific antagonist D(-)-2-amino-5-phosphonopentanoic acid, excluding the contamination of responses to mGluR agonists by nonspecific cross-reactivity with NMDA receptors. Picrotoxin did not prevent the inhibitory action of L-CCG-I and L-AP4. We conclude that mGluRs, probably similar to those belonging to groups I, II, and III described in mammals, may play a role as modulators of gastric circuit rhythm generation in vivo.

A receptor with GABAC-like pharmacology in invertebrate neurones in culture.

We have characterized in crustacean neurones in culture a receptor for gamma-aminobutyric acid (GABA) which conforms to the pharmacological profile of the proposed type-C GABA receptor (GABAC) found in the vertebrate retina. It is associated with a chloride-selective ion channel and is blocked by picrotoxin. It is neither inhibited by bicuculline nor activated by baclofen, while diazepam and phenobarbital are without modulatory effect. Like the GABAC-like receptor of the vertebrate retina it is activated by the folded GABA analogue cis-4-aminocrotonic acid (CACA). Desensitization is moderate allowing for a more sustained action of GABA. Single channel recordings revealed a bicuculline-resistant GABA- and CACA-activated chloride channel with a conductance about eight times higher than that described for the bicuculline-resistant GABA receptor channel from the rat retina.

BICUCULLINE/BACLOFEN-INSENSITIVE GABA RESPONSE IN CRUSTACEAN NEURONES IN CULTURE

Neurones were dissociated from thoracic ganglia of embryonic and adult lobsters and kept in primary culture. When gamma-aminobutyric acid (GABA) was applied by pressure ejection, depolarizing or hyperpolarizing responses were produced, depending on the membrane potential. They were accompanied by an increase in membrane conductance. When they were present, action potential firing was inhibited. The pharmacological profile and ionic mechanism of GABA-evoked current were investigated under voltage-clamp with the whole-cell patch-clamp technique. The reversal potential of GABA-evoked current depended on the intracellular and extracellular Cl- concentration but not on extracellular Na+ and K+. Blockade of Ca2+ channels by Mn2+ was also without effect. The GABA-evoked current was mimicked by application of the GABAA agonists muscimol and isoguvacine with an order of potency muscimol>GABA>isoguvacine. cis-4-aminocrotonic acid (CACA), a folded and conformationally restricted GABA analogue, supposed to be diagnostic for the vertebrate GABAC receptor, also induced a bicuculline-resistant chloride current, although with a potency about 10 times lower than that of GABA. The GABA-evoked current was largely blocked by picrotoxin, but was insensitive to the GABAA antagonists bicuculline, bicuculline methiodide and SR 95531 at concentrations of up to 100 µmol l-1. Diazepam and phenobarbital did not exert modulatory effects. The GABAB antagonist phaclophen did not affect the GABA-induced current, while the GABAB agonists baclophen and 3-aminopropylphosphonic acid (3-APA) never evoked any response. Our results suggest that lobster thoracic neurones in culture express a chloride-conducting GABA-receptor channel which conforms to neither the GABAA nor the GABAB types of vertebrates but shows a pharmacology close to that of the novel GABAC receptor described in the vertebrate retina.

Practical identification of functional expansions of nonlinear systems submitted to non-Gaussian inputs.

Time-domain identification of nonlinear systems represented by functional expansions is considered. A general framework is defined for the analysis of three identification methods: the widely used cross-correlation method, Korenberg's method, and a suboptimal least-squares method based on a stochastic approximation algorithm. First, the major characteristics of the underlying estimation problem are pointed out. Then, the identification methods are interpreted as approximations to an optimal estimator, which helps gain insight into their internal functioning and to the investigation of their connections and differences. Examination of results previously published and of the simulations reported in this article indicate that stochastic approximation is an interesting alternative to other existing methods. Identification of a biological system stimulated by a non-Gaussian input confirms the practicality of this approach.

Interpretation of functional series expansions.

While much research has been devoted to the implementation and application of Volterra and Wiener functional series expansions in the identification and characterization of biological systems, little effort has been focused on the fundamental problem of interpreting the resulting kernels. This paper describes the application of the series to the components of a known model of the human pupil control system. As more complicated elements are put together, insight into kernel interpretation is built up incrementally until the total system is identified. Practical limitations and methods are also discussed.

Light and target distance interact to control pupil size.

Light and target distance stimuli were presented to normal human subjects, and their pupillary responses were measured. A homeomorphic computer model of the pupillary control system is presented in which the form of interaction of controller signals due to light and target distance was investigated. The error remaining when model parameters were optimized to fit experimental pupil size (area or diameter) was smaller for the linear interaction hypothesis than for either power law or logical law interaction. A generalized second-order nonlinear model with six parameters (vs. 3 for each of the other models) yielded somewhat lower residual error. With the use of a modified Akaike information criterion, the value (in an information theoretic sense) of the improved fit afforded by the three additional parameters in the generalized nonlinear model was shown to be small, and thus the generalized second-order nonlinear model was rejected in favor of the simpler and more parsimonious linear model.

Morphological and electrophysiological properties of the electromotoneurones of the electric ray Torpedo marmorata in vivo and in in vitro brain slices.

The morphology of the adult electromotoneurones of the electric ray Torpedo marmorata has been investigated by intracellular injection of horseradish peroxidase. The results show particularly small dendritic fields, poor dendritic branching, and the existence of two distinct types of dendrites. The electrophysiological data demonstrate that the electromotoneurones behave similarly in vivo and in in vitro brain slices. Observations on spontaneous and stimulus-evoked postsynaptic potentials suggest quantal release of transmitter in the Torpedo central nervous system.

Systems model for pupil size effect. II. Feedback model.

The human pupillary control system has been the subject of interest to biologists and engineers as an example of a sensorimotor reflex which can be embedded in a control system paradigm. We present a nonlinear feedback model whose compact structure allows us to hypothesize possible physiological mechanisms which generate the proper behavior of the pupil system. The important pupil responses, including pupil size effect, asymmetry, and response the high-frequency stimuli, are defined. This model was simulated on a digital computer and comparisons to the paradigm experimental responses were performed, demonstrating a fit to each of the observed conditions. Improvements on previous models are discussed.

Electrophysiological aspects of synaptic transmission at the electromotor junction of Torpedo marmorata.

Miniature and stimulus-evoked electroplaque potentials were recorded in Torpedo electrocytes intracellularly and extracellularly and analysed quantitatively. Tetrodotoxin reversibly blocked stimulus evoked potentials but hardly affected spontaneous miniature potentials in amplitude and frequency. The quantum content of stimulus-evoked potentials varied between 150 and 400 in normal saline and decreased in low Ca2+ high Mg2+ solution. Quantal release conformed to binomial statistics and allowed determination of the release parameters p and n. Analysis of the time constant of decay of spontaneous miniature electroplaque currents showed variation around a mean of 0.75 +/- 0.16 msec (SD) which was greatly prolonged by application of neostigmine.

A systems model for the pupil size effect. I. Transient data.

The human pupillary control system is a paradigm for linearized biological control systems. It also exhibits a series of interesting nonlinear behaviors, particularly asymmetry, "pupillary escape," and "pupillary capture." We present a nonlinear model in which a signal dependent upon pupil size is fed back internally to cause a change in system parameters related to gains and rates of light adaptation. The model was simulated on a digital computer, a variety of experimental data was well matched, and improvements over previous pupil models demonstrated. A candidate physiological mechanism for adaptive components of the model might have the form of an inverse "Henneman coded" neuronal pool.