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J P Lindemann

Publications and source records attributed to J P Lindemann.

At least 19 recordsLinked to original sources

Responses of blowfly motion-sensitive neurons to reconstructed optic flow along outdoor flight paths.

The retinal image flow a blowfly experiences in its daily life on the wing is determined by both the structure of the environment and the animal's own movements. To understand the design of visual processing mechanisms, there is thus a need to analyse the performance of neurons under natural operating conditions. To this end, we recorded flight paths of flies outdoors and reconstructed what they had seen, by moving a panoramic camera along exactly the same paths. The reconstructed image sequences were later replayed on a fast, panoramic flight simulator to identified, motion sensitive neurons of the so-called horizontal system (HS) in the lobula plate of the blowfly, which are assumed to extract self-motion parameters from optic flow. We show that under real life conditions HS-cells not only encode information about self-rotation, but are also sensitive to translational optic flow and, thus, indirectly signal information about the depth structure of the environment. These properties do not require an elaboration of the known model of these neurons, because the natural optic flow sequences generate--at least qualitatively--the same depth-related response properties when used as input to a computational HS-cell model and to real neurons.

Animals↗

On the computations analyzing natural optic flow: quantitative model analysis of the blowfly motion vision pathway.

For many animals, including humans, the optic flow generated on the eyes during locomotion is an important source of information about self-motion and the structure of the environment. The blowfly has been used frequently as a model system for experimental analysis of optic flow processing at the microcircuit level. Here, we describe a model of the computational mechanisms implemented by these circuits in the blowfly motion vision pathway. Although this model was originally proposed based on simple experimenter-designed stimuli, we show that it is also capable to quantitatively predict the responses to the complex dynamic stimuli a blowfly encounters in free flight. In particular, the model visual system exploits the active saccadic gaze and flight strategy of blowflies in a similar way, as does its neuronal counterpart. The model circuit extracts information about translation velocity in the intersaccadic intervals and thus, indirectly, about the three-dimensional layout of the environment. By stepwise dissection of the model circuit, we determine which of its components are essential for these remarkable features. When accounting for the responses to complex natural stimuli, the model is much more robust against parameter changes than when explaining the neuronal responses to simple experimenter-defined stimuli. In contrast to conclusions drawn from experiments with simple stimuli, optimization of the parameter set for different segments of natural optic flow stimuli do not indicate pronounced adaptational changes of these parameters during long-lasting stimulation.

Adaptation, Physiological↗

Visually guided orientation in flies: case studies in computational neuroethology.

To understand the functioning of nervous systems and, in particular, how they control behaviour we must bridge many levels of complexity from molecules, cells and synapses to perception behaviour. Although experimental analysis is a precondition for understanding by nervous systems, it is in no way sufficient. The understanding is aided at all levels of complexity by modelling. Modelling proved to be an inevitable tool to test the experimentally established hypotheses. In this review it will by exemplified by three case studies that the appropriate level of modelling needs to be adjusted to the particular computational problems that are to be solved. (1) Specific features of the highly virtuosic pursuit behaviour of male flies can be understood on the basis of a phenomenological model that relates the visual input to the motor output. (2) The processing of retinal image motion as is experienced by freely moving animals can be understood on the basis of a model consisting of algorithmic components and components which represent a simple equivalent circuit of nerve cells. (3) Behaviourally relevant features of the reliability of encoding of visual motion information can be understood by modelling the transformation of postsynaptic potentials into sequences of spike trains.

Animals↗

FliMax, a novel stimulus device for panoramic and highspeed presentation of behaviourally generated optic flow.

A high-speed panoramic visual stimulation device is introduced which is suitable to analyse visual interneurons during stimulation with rapid image displacements as experienced by fast moving animals. The responses of an identified motion sensitive neuron in the visual system of the blowfly to behaviourally generated image sequences are very complex and hard to predict from the established input circuitry of the neuron. This finding suggests that the computational significance of visual interneurons can only be assessed if they are characterised not only by conventional stimuli as are often used for systems analysis, but also by behaviourally relevant input.

Animals↗

Neuronal processing of behaviourally generated optic flow: experiments and model simulations.

The stimuli traditionally used for analysing visual information processing are much simpler than what an animal sees when moving in its natural environment. Therefore, we analysed in a previous study the performance of an identified neuron in the optomotor system of the fly by using as visual stimuli image sequences that were experienced by the animal while walking in a structured environment. These electrophysiological experiments revealed that the fly visual system computes from behaviourally generated optic flow a rather unambiguous representation of the animal's self-motion. In contrast to conclusions based on simple stimuli, the directions of turns are represented by an interneuron, the HSE cell, quite independent of the spatial layout of the environment and its textural properties when the cell is stimulated with behaviourally generated optic flow. This conclusion is substantiated here by further experimental evidence. Moreover, it is shown that the largely unambiguous responses of the HSE cell to behaviourally generated optic flow can be replicated to a large extent by a network model of the fly's visual motion pathway. These results stress the significance of naturalistic stimuli for analysing what is encoded by neuronal circuits under natural operating conditions.

Algorithms↗

The positive inotropic effect of alpha 1A-adrenoceptor stimulation is inhibited by 4-aminopyridine.

This study was designed to determine if 4-aminopyridine, a reported inhibitor of the transient outward K+ current (Ito), alters the inotropic actions elicited via stimulation of WB4101- or chloroethylclonidine-sensitive receptors in rat myocardium. WB4101 (N-[2-(2, 6-dimethoxyphenoxy)ethyl]-2,3-dihydro-1,4-benzodioxin-2-m ethanamine) is a competitive antagonist that is selective for alpha 1A- and alpha 1C-adrenoceptors, while chloroethylclonidine is an irreversible blocker that is reported to antagonize alpha 1B-, alpha 1C-, and alpha 1D-adrenoceptor binding. Inotropic effects of the alpha 1-adrenoceptor agonist phenylephrine were examined in isolated left atrial and papillary muscle before and after addition of 4-aminopyridine, and before and after addition of 4-aminopyridine in preparations pretreated with chloroethylclonidine or WB4101. In addition, effects of phenylephrine were examined before and after treatment with staurosporine (an inhibitor of protein kinase C) in chloroethylclonidine-pretreated preparations. Phenylephrine (10 microM) elicited a sustained positive inotropic response in left atria and a triphasic inotropic action in papillary muscle (transient positive and negative inotropic components preceding a sustained positive inotropic response). 4-Aminopyridine (1.0, 1.7, 3.0 mM) reduced the sustained positive inotropic responses in the absence of antagonists and in chloroethylclonidine-pretreated preparations. However, in the presence of 10 nM WB4101, 4-aminopyridine had no effect on the remaining inotropic actions of phenylephrine. The sustained positive inotropic response to the alpha 1-agonist in chloroethylclonidine-pretreated preparations was not inhibited by 100 nM staurosporine. These data suggest that the sustained positive inotropic actions of alpha 1A-adrenoceptor stimulation in rat atrial and ventricular myocardium are mediated via non-protein kinase C-associated reductions in Ito.

4-Aminopyridine↗

Effects of extracellular Cl- on the inotropic response to alpha-adrenoceptor stimulation.

This study was designed to determine if the sustained positive inotropic action of alpha-adrenergic stimulation is affected by the absence of extracellular chloride ion (Clo-). Atrial and papillary muscle were isolated from adult male rats, bathed in Krebs-Henseleit solution (30 degrees C) with and without Cl- (methane-sulfonate substitution), and stimulated at 0.5 Hz. Isometric developed tension was monitored during cumulative addition of phenylephrine, isoproterenol and Ca2+. The dose-dependent positive inotropic effects of isoproterenol and Ca2+ were not altered by the absence of Clo-. However, the magnitude of the response to phenylephrine was diminished in both tissues. In atrial muscle, the maximum positive inotropic effect of phenylephrine was reduced from 2.05 +/- 0.17 g in the presence of Clo- to 0.39 +/- 0.06 g in the absence of Clo-; control developed tension was 0.60 +/- 0.08 and 0.47 +/- 0.10 g in these two groups before exposure to the alpha-adrenoceptor agonist. In papillary muscle, control developed tension was 1.40 +/- 0.11 and 1.17 +/- 0.18 g in the presence and absence of Clo-, respectively; and the maximum inotropic responses to phenylephrine were 0.71 +/- 0.12 and 0.27 +/- 0.13 g. EC50 values for phenylephrine were not significantly affected by substitution for Cl-. Similar results were observed in a Hepes-buffered bathing solution without bicarbonate (HCO3-). These results indicate that the positive inotropic action of alpha-adrenergic stimulation is mediated in part by a mechanism requiring Cl-. Furthermore, data suggest that the antagonistic effect of Clo- removal is not mediated via Cl-/HCO3- exchange.

Adrenergic alpha-Agonists↗

Alpha 1a-adrenergic receptor mediated positive chronotropic effect in right atria isolated from rats.

Experiments in right atria isolated from adult male rats were designed to determine which of the alpha 1-adrenergic receptor (alpha 1-AR) subtypes are involved in the positive chronotropic effect of phenylephrine, an alpha 1-AR agonist. Chloroethylclonidine (CEC), an irreversible alpha 1b-, alpha 1c-, and alpha 1d-AR antagonist, did not alter the efficacy or potency of phenylephrine; however, CEC did elicit a concentration-dependent negative chronotropic effect and reduce the absolute maximum spontaneous rate observed in the presence of phenylephrine. WB4101, a competitive alpha 1a- and alpha 1c-AR-selective antagonist, did not alter basal spontaneous rate or the efficacy of phenylephrine, but it did produce a significant rightward shift of the phenylephrine concentration-response curve. Phenoxybenzamine, an irreversible nonselective alpha-AR antagonist, elicited a concentration-dependent negative chronotropic effect, a significant rightward shift of the phenylephrine concentration-response curve, and a reduction in the efficacy of phenylephrine. The chronotropic action of the beta-adrenergic agonist isoproterenol was not affected by CEC, WB4101, or phenoxybenzamine. These data suggest that the positive chronotropic effect of alpha 1-adrenergic agonists in rat right atria is mediated via stimulation of alpha 1a-ARs.

Adrenergic alpha-1 Receptor Antagonists↗

WB4101- and CEC-sensitive positive inotropic actions of phenylephrine in rat cardiac muscle.

This study was designed to determine the role of the alpha 1-adrenergic receptor (AR) subtypes in the positive inotropic action of alpha 1-adrenergic agonists in rat myocardium. Isolated left atrial and papillary muscle were suspended in oxygenated Krebs-Henseleit buffer (37 degrees C) containing 3 microM nadolol and paced at 3.3 Hz. Isometric tension was continuously monitored. Cumulative concentration-response curves for phenylephrine (3 x 10(-7) to 3 x 10(-4) M) were obtained in the presence and absence of WB4101 (4 and 10 nM) and with and without treatment with chloroethylclonidine (CEC; 10, 100, and 300 microM). WB4101 antagonized the effect of phenylephrine in both tissues, increasing half-maximal effective concentration (EC50) values in a concentration-dependent manner. CEC pretreatment also increased EC50 values in both tissues, and 300 microM CEC reduced the maximal positive inotropic effect of phenylephrine by approximately 48 and 38% in left atrial and papillary muscle, respectively. CEC alone elicited significant increases in contractile force that were not readily reversible. These data suggest that the positive inotropic effect of alpha 1-adrenergic agonists in rat atrial and ventricular myocardium results from stimulation of both WB4101- and CEC-sensitive alpha 1-ARs.

Adrenergic alpha-Antagonists↗

Effects of WB4101 and chloroethylclonidine on the positive and negative inotropic actions of phenylephrine in rat cardiac muscle.

This study was designed to determine if the positive and negative inotropic actions of alpha-1-adrenergic agonists in rat atrial and ventricular myocardium are mediated via different alpha-1-adrenergic receptor (AR) subtypes. Inotropic effects of phenylephrine were examined in isolated left atrial and papillary muscle before and after treatment with prazosin, WB4101 (N-[2-(2,6-dimethoxyphenoxy)ethyl]-2,3-dihydro-1,4-benzodioxin+ ++-2-methanamine), chloroethylclonidine (CEC) and WB4101 plus CEC. Phenylephrine (10 microM) elicited a monophasic positive inotropic response in left atrial muscle and a triphasic inotropic action in papillary muscle (transient positive, then negative inotropic components preceding a sustained positive inotropic response). CEC, WB4101 and prazosin each antagonized the monophasic response in isolated left atria and the sustained positive inotropic response in papillary muscle. CEC and prazosin each antagonized the transient negative inotropic component in papillary muscle. The transient positive inotropic response was not affected by CEC, WB4101 or CEC plus WB4101, but was antagonized by higher concentrations of prazosin. These data suggest that the sustained positive inotropic effect of alpha-1-adrenergic agonists in rat atrial and ventricular myocardium results from stimulation of alpha-1A and alpha-1B ARs, whereas the transient negative inotropic component of the triphasic response in ventricular preparations is mediated via alpha-1B ARs. However, present data do not exclude the possibility that the CEC-sensitive inotropic responses elicited by phenylephrine may be mediated in part by other recently described alpha-1 subtypes. The receptors involved in the transient positive inotropic action cannot be identified by current results.

Adrenergic alpha-1 Receptor Antagonists↗

Alpha 1b-adrenoceptor-mediated stimulation of Na-K pump current in adult rat ventricular myocytes.

The purpose of this study was to determine if myocardial alpha 1a-and/or alpha 1b-adrenoceptors are involved in the increase in Na-K pump current (Ip) elicited by alpha 1-adrenergic agonists. Single rat ventricular myocytes were isolated by enzymatic disaggregation. The whole cell patch-clamp technique was used to examine dose-dependent effects of phenylephrine (PE) on holding current (Ih) and to determine whether observed actions were mediated via alpha 1a-or alpha 1b-adrenergic receptors. To minimize the contribution of transsar-colemmal currents other than Ip to Ih, membrane voltage was held constant -40 mV, and cells were maintained in a Ca-free perfusate containing 1 mM Ba and 0.1 mM Cd. All experiments were conducted in the presence of 3 microM nadolol. PE elicited dose-dependent increases in Ih, with a peak effect of 0.57 +/- 0.03 pA/pF observed at 30 microM. The response to PE was dose dependently inhibited by prazosin and chloroethylclonidine and was totally eliminated by 1 mM ouabain. When used at doses selective for the alpha 1a-subtype, WB4101 failed to significantly antagonize the action of PE. These data suggest that the observed alpha 1-adrenoceptor-mediated increase in Ih in isolated rat ventricular myocytes is the result of an increase in Ip effected via stimulation of alpha 1b-adrenergic receptors.

Adrenergic alpha-Antagonists↗

Contractile protein alterations in heart failure.

After nearly three decades of intense investigation, the precise cellular mechanisms underlying impaired contractility in heart failure remain to be defined. Nevertheless, growing use of the tools of molecular biology promises new insights into how alterations of contractile proteins mediate the functional derangements of failure.

Actins↗