Interactions of Nereistoxin and Its Analogs with Vertebrate Nicotinic Acetylcholine Receptors and Molluscan ACh Binding Proteins

Nereistoxin (NTX) is a marine toxin isolated from an annelid worm that lives along the coasts of Japan. Its insecticidal properties were discovered decades ago and this stimulated the development of a variety of insecticides such as Cartap that are readily transformed into NTX. One unusual feature of NTX is that it is a small cyclic molecule that contains a disulfide bond. In spite of its size, it acts as an antagonist at insect and mammalian nicotinic acetylcholine receptors (nAChRs). The functional importance of the disulfide bond was assessed by determining the effects of inserting a methylene group between the two sulfur atoms, creating dimethylaminodithiane (DMA-DT). We also assessed the effect of methylating the NTX and DMA-DT dimethylamino groups on binding to three vertebrate nAChRs. Radioligand receptor binding experiments were carried out using washed membranes from rat brain and fish (Torpedo) electric organ; [3H]-cytisine displacement was used to assess binding to the predominantly high affinity alpha4beta2 nAChRs and [125I]-alpha-bungarotoxin displacement was used to measure binding of NTX and analogs to the alpha7 and skeletal muscle type nAChRs. While the two quaternary nitrogen analogs, relative to their respective tertiary amines, displayed lower α4β2 nAChR binding affinities, both displayed much higher affinities for the Torpedo muscle nAChR and rat alpha7 brain receptors than their respective tertiary amine forms. The binding affinities of DMA-DT for the three nAChRs were lower than those of NTX and MeNTX. An AChBP mutant lacking the C loop disulfide bond that would potentially react with the NTX disulfide bond displayed an NTX affinity very similar to the parent AChBP. Inhibition of [3H]-epibatidine binding to the AChBPs was not affected by exposure to NTX or MeNTX for up to 24 hr prior to addition of the radioligand. Thus, the disulfide bond of NTX is not required to react with the vicinal disulfide in the AChBP C loop for inhibition of [3H]-epibatidine binding. However, a reversible disulfide interchange reaction of NTX with nAChRs might still occur, especially under reducing conditions. Labeled MeNTX, because it can be readily prepared with high specific radioactivity and possesses relatively high affinity for the nAChR-rich Torpedo nAChR, would be a useful probe to detect and identify any nereistoxin adducts.

From Columbia Studio B to Carnegie Hall: The Studio-to-Stage Creative Trajectory in the Fusion Jazz of Miles Davis

<p>This thesis proposes an interrelationship between the creative processes of the recording studio and the concert stage in the fusion jazz of Miles Davis. Recent scholarship highlights the importance of the recording studio to fusion jazz musicians as they developed unique approaches to composition and improvisation. While providing valuable insight into the studio-derived creative processes distinctive of fusion jazz, this scholarship inadvertently obscures some of the live performance practices of fusion jazz musicians. Turning attention towards live performance, yet without neglecting the insights of this recent scholarship, I consider how the creative processes forged by Davis in the recording studio manifested in his activities as a concert artist. Combining commentary on Davis’s formative fusion jazz studio recordings (produced between 1969 and 1972) with analyses of the live album Dark Magus (exemplary of his mid-1970s concert performances), this thesis suggests a reorientation in Davis’s conceptions of improvisation and composition during this period by highlighting some of the creative processes he engaged in, both in the recording studio and on the concert stage. Drawing on the accounts of several musicians who worked with Davis in the recording studio during the late-1960s and early-1970s, I consider how post production tape editing allowed Davis and his band a new means for composing and improvising in the studio. Then, to demonstrate what I have termed a studio-to-stage creative trajectory, I analyse two creative processes common to Davis’s mid-1970s concerts as evidenced in Dark Magus: Davis’s on-stage direction of sudden, rhythm section cuts in the midst of lead instrumentalists’ improvisations; and the featured use of two accompanimental instruments unusual to jazz performance—a YC45 electric organ (played by Davis ) and a drum machine (played by percussionist James Mtume). Finally, framing this studio-to-stage creative trajectory in terms of performance theorist Philip Auslander’s concept of liveness, I claim that Davis’s fusion jazz stands as an example of mediatization rich in human agency. I then suggest that the work of other fusion jazz musicians and musicians associated with other jazz styles could be usefully reappraised using a similar methodology that explores the role of record production in creative process</p>

From Columbia Studio B to Carnegie Hall: The Studio-to-Stage Creative Trajectory in the Fusion Jazz of Miles Davis

<p>This thesis proposes an interrelationship between the creative processes of the recording studio and the concert stage in the fusion jazz of Miles Davis. Recent scholarship highlights the importance of the recording studio to fusion jazz musicians as they developed unique approaches to composition and improvisation. While providing valuable insight into the studio-derived creative processes distinctive of fusion jazz, this scholarship inadvertently obscures some of the live performance practices of fusion jazz musicians. Turning attention towards live performance, yet without neglecting the insights of this recent scholarship, I consider how the creative processes forged by Davis in the recording studio manifested in his activities as a concert artist. Combining commentary on Davis’s formative fusion jazz studio recordings (produced between 1969 and 1972) with analyses of the live album Dark Magus (exemplary of his mid-1970s concert performances), this thesis suggests a reorientation in Davis’s conceptions of improvisation and composition during this period by highlighting some of the creative processes he engaged in, both in the recording studio and on the concert stage. Drawing on the accounts of several musicians who worked with Davis in the recording studio during the late-1960s and early-1970s, I consider how post production tape editing allowed Davis and his band a new means for composing and improvising in the studio. Then, to demonstrate what I have termed a studio-to-stage creative trajectory, I analyse two creative processes common to Davis’s mid-1970s concerts as evidenced in Dark Magus: Davis’s on-stage direction of sudden, rhythm section cuts in the midst of lead instrumentalists’ improvisations; and the featured use of two accompanimental instruments unusual to jazz performance—a YC45 electric organ (played by Davis ) and a drum machine (played by percussionist James Mtume). Finally, framing this studio-to-stage creative trajectory in terms of performance theorist Philip Auslander’s concept of liveness, I claim that Davis’s fusion jazz stands as an example of mediatization rich in human agency. I then suggest that the work of other fusion jazz musicians and musicians associated with other jazz styles could be usefully reappraised using a similar methodology that explores the role of record production in creative process</p>

The captivating effect of electric organ discharges: species, sex, and orientation are embedded in every single received image

Some fish communicate using pulsatile, stereotyped electric organ discharges (EODs) that exhibit species- and sex-specific time courses. To ensure reproductive success, they must be able to discriminate conspecifics from sympatric species in the muddy waters they inhabit. We have previously shown that they use the electric field lines as a tracking guide to approach conspecifics (electrotaxis) in both Gymnotus and Brachyhypopomus genera. Here we show that the social species Brachyhypopomus gauderio uses electrotaxis to arrive abreast a conspecific, coming from behind. Stimulus image analysis shows that, even in a uniform field, every single EOD causes an image in which the gradient and the local field time courses contain enough information to allow the fish to evaluate conspecific sex, and to find the path to reach it. Using a forced-choice test we show that sexually mature individuals orient themselves along a uniform field in the direction encoded by the time course characteristic of the opposite sex. This indicates that these fish use the stimulus image profile as a spatial guidance clue to find a mate. Embedding species, sex, and orientation cues is a particular example of how species can encode multiple messages in the same self-generated communication signal carrier, allowing for other signal parameters (e.g., EOD timing) to carry additional, often circumstantial, messages. This ‘multiple messages’ EOD embedding approach expressed in this species is likely to be a common and successful strategy widespread across evolutionary lineages and among varied signaling modalities.

Derived loss of signal complexity and plasticity in a genus of weakly electric fish

Signal plasticity can maximize the usefulness of costly animal signals such as the electric organ discharges (EODs) of weakly electric fishes. Some species of the order Gymnotiformes rapidly alter their EOD amplitude and duration in response to circadian cues and social stimuli. How this plasticity is maintained across related species with different degrees of signal complexity is poorly understood. In one genus of weakly electric gymnotiform fish (Brachyhypopomus) only one species, B. bennetti, produces a monophasic signal while all other species emit complex biphasic or multiphasic EOD waveforms produced by two overlapping but asynchronous action potentials in each electric organ cell (electrocyte). One consequence of this signal complexity is the suppression of low-frequency signal content that is detectable by electroreceptive predators. In complex EODs, reduction of the EOD amplitude and duration during daytime inactivity can decrease both predation risk and the metabolic cost of EOD generation. We compared EOD plasticity and its underlying physiology in Brachyhypopomus focusing on B. bennetti. We found that B. bennetti exhibits minimal EOD plasticity, but that its electrocytes retained vestigial mechanisms of biphasic signaling and vestigial mechanisms for modulating the EOD amplitude. These results suggest that this species represents a transitional phenotypic state within a clade where signal complexity and plasticity were initially gained and then lost. Signal mimicry, mate recognition, and sexual selection are potential factors maintaining the monophasic EOD phenotype in the face of detection by electroreceptive predators.

Glutamatergic Control Of A Pattern-Generating Central Nucleus In A Gymnotiform Fish

The activity of central pattern-generating networks (CPGs) may change under the control exerted by various neurotransmitters and modulators to adapt its behavioral outputs to different environmental demands. Although the mechanisms underlying this control have been well established in invertebrates, most of their synaptic and cellular bases are not yet well understood in vertebrates. Gymnotus omarorum, a pulse-type gymnotiform electric fish, provides a well-suited vertebrate model to investigate these mechanisms. G. omarorum emits rhythmic and stereotyped electric organ discharges (EODs), which function in both perception and communication, under the command of an electromotor CPG. This nucleus is composed of electrotonically coupled intrinsic pacemaker cells, which pace the rhythm, and bulbospinal projecting relay cells that contribute to organize the pattern of the muscle-derived effector activation that produce the EOD. Descending influences target CPG neurons to produce adaptive behavioral electromotor responses to different environmental challenges. We used electrophysiological and pharmacological techniques in brainstem slices of G. omarorum to investigate the underpinnings of the fast transmitter control of its electromotor CPG. We demonstrate that pacemaker, but not relay cells, are endowed with ionotropic and metabotropic glutamate receptor subtypes. We also show that glutamatergic control of the CPG likely involves two types of synapses contacting pacemaker cells, one type containing both AMPAR-NMDAR receptors and the other one only-NMDAR. Fast neurotransmitter control of vertebrate CPGs seems to exploit the kinetics of the involved postsynaptic receptors to command different behavioral outputs. The prospect of common neural designs to control CPG activity in vertebrates is discussed.

The third form electric organ discharge of electric eels

The electric eel is a unique species that has evolved three electric organs. Since the 1950s, electric eels have generally been assumed to use these three organs to generate two forms of electric organ discharge (EOD): high-voltage EOD for predation and defense and low-voltage EOD for electrolocation and communication. However, why electric eels evolved three electric organs to generate two forms of EOD and how these three organs work together to generate these two forms of EOD have not been clear until now. Here, we present the third form of independent EOD of electric eels: middle-voltage EOD. We suggest that every form of EOD is generated by one electric organ independently and reveal the typical discharge order of the three electric organs. We also discuss hybrid EODs, which are combinations of these three independent EODs. This new finding indicates that the electric eel discharge behavior and physiology and the evolutionary purpose of the three electric organs are more complex than previously assumed. The purpose of the middle-voltage EOD still requires clarification.