Michael R. Markham

Regulation and modulation of electric waveforms in gymnotiform electric fish

Weakly electric gymnotiform fish specialize in the regulation and modulation of the action potentials that make up their multi-purpose electric signals. To produce communication signals, gymnotiform fish modulate the waveforms of their electric organ discharges (EODs) over timescales spanning ten orders of magnitude within the animal’s life cycle: developmental, reproductive, circadian, and behavioral. Rapid changes lasting milliseconds to seconds are the result of direct neural control of action potential firing in the electric organ. Intermediate-term changes taking minutes to hours result from the action of melanocortin peptides, the pituitary hormones that induce skin darkening and cortisol release in many vertebrates. Long-term changes in the EOD waveform taking days to weeks result from the action of sex steroids on the electrocytes in the electric organ as well as changes in the neural control structures in the brain. These long-term changes in the electric organ seem to be associated with changes in the expression of voltage-gated ion channels in two gene families. Electric organs express multiple voltage-gated sodium channel genes, at least one of which seems to be regulated by androgens. Electric organs also express multiple subunits of the shaker (Kv1) family of voltage-gated potassium channels. Expression of the Kv1 subtype has been found to vary with the duration of the waveform in the electric signal. Our increasing understanding of the mechanisms underlying precise control of electric communication signals may yield significant insights into the diversity of natural mechanisms available for modifying the performance of ion channels in excitable membranes. These mechanisms may lead to better understanding of normal function in a wide range of physiological systems and future application in treatment of disease states involving pathology of excitable membranes.

Serotonin modulates the electric waveform of the gymnotiform electric fish Brachyhypopomus pinnicaudatus.

SUMMARY The gymnotiform electric fish Brachyhypopomus pinnicaudatus communicates with a sexually dimorphic electric waveform, the electric organ discharge (EOD). Males display pronounced circadian rhythms in the amplitude and duration of their EODs. Changes in the social environment influence the magnitudes of these circadian rhythms and also produce more transient responses in the EOD waveforms. Here we show that injections of serotonin produce quick, transient, dose-dependent enhancements of the male EOD characters similar to those induced by encounters with another male. The response to serotonin administered peripherally begins 5-10 min post injection and lasts approximately 3 h. The magnitude of the response to serotonin is tightly associated with the magnitude of the day-to-night swing of the circadian rhythm prior to injection. Taken together these findings suggest that the males social environment influences his response to serotonin by altering the function of some part of the downstream chain between the serotonin receptors and the ion channels involved in control of the EOD waveform. Although chronic activation of serotonin circuitry is widely known to elicit subordinate behavior, we find that 5-HT initially increases a dominance signal in these fish. These findings are consistent with the emerging view that serotonin facilitates different adaptive responses to acute and chronic social challenge and stress.

Circadian and social cues regulate ion channel trafficking

Electric fish strengthen their communication signals nightly and during social encounters by rapidly trafficking ion channels into cell membranes, demonstrating a direct relationship between environmental stimuli, channel trafficking, and behavior.

Adrenocorticotropic Hormone Enhances the Masculinity of an Electric Communication Signal by Modulating the Waveform and Timing of Action Potentials within Individual Cells

We report here that melanocortin peptides appear to serve as the mechanism by which weakly electric fish couple socially regulated and stress-regulated brain pathways to unique changes in the intrinsic excitability and action potential waveform of excitable membranes in peripheral cells involved in communication. Gymnotiform electric fish modulate their electric organ discharges (EODs) by reshaping the electric discharges of excitable cells in the periphery. These fish show circadian enhancement of the EOD waveform. They also enhance their EOD waveforms within minutes in response to stressors and changes in the social environment, thus altering the communication value of the signal. Changes in the EOD waveform that occur within minutes result from changes in the discharges of individual electrocytes (μEODs) mediated by the cAMP/protein kinase A (PKA) pathway acting on ion channel kinetics. What activates the cAMP/PKA pathway in electrocytes has not been identified. In vivo injections of the melanocortin peptide adrenocorticotropic hormone (ACTH) increase the amplitude and duration of the electric signal waveform of the gymnotiform Brachyhypopomus pinnicaudatus over the course of 1 h. Applied to single electrocytes in vitro, ACTH increases μEOD amplitude and duration within minutes by differentially modulating the action potentials of the two excitable membranes of the electrocyte and changing the timing of these two spikes. Serotonin modulates the EOD in vivo but has no effect on the μEOD in vitro. The cAMP analog 8-bromo-cAMP mimicked the effects of ACTH, whereas inhibition of PKA by protein kinase A inhibitor 14–22 amide blocked the modulatory effects of ACTH, confirming the role of the cAMP/PKA pathway in μEOD modulation by ACTH.

Treating a heterogeneous set of anxiety disorders in youths with group cognitive behavioral therapy: A partially nonconcurrent multiple-baseline evaluation

This study investigated the efficacy of Group Cognitive Behavioral Therapy (GCBT) in the treatment of a heterogeneous set of anxiety disorders in children and adolescents using a partially nonconcurrent multiple-baseline across groups design with 12 clinically referred youth between 6 and 16 years of age who met DSM-IV criteria for an anxiety disorder. Targeted diagnoses included specific phobia, separation anxiety disorder, social phobia, generalized anxiety disorder, and obsessive-compulsive disorder, with 3 of the children also presenting with school refusal behavior. Duration of baseline for each of the 3 groups varied and ran for 1, 2, or 3 weeks. Dependent measures included diagnostic status, daily child and parent ratings of child anxiety severity, and child- and parent-completed questionnaires. Results indicated that GCBT was generally efficacious in reducing anxious symptoms in youth treated in diagnostically heterogeneous groups, and that gains were generally maintained at 6 and 12 month follow-ups. Findings are discussed in terms of their theoretical and practical implications for the efficient treatment of children and adolescents with anxiety disorders.

8 Stimulus classes and the untrained acquisition of stimulus functions

Publisher Summary The chapter discusses stimulus classes and the untrained acquisition of stimulus functions. The relation between stimulus classes and the untrained acquisition or emergence of stimulus function is interesting and complex. However, one of the problems in interpreting and integrating the stimulus class literature is that there is an inconsistent terminology for talking about stimulus classes. The other problem is the identification of the prerequisites for the formation of stimulus classes and the variables that control their union. The stimulus classes were distinguished among three types of classes: (1) stimulus classes, (2) functional equivalence classes, and (3) stimulus equivalence classes (Dougher and Markham). The chapter provides a conceptual scheme for integrating the various findings from the stimulus class literature and identifies the classes of variables that may shed light on the relevant issues in the field. Untrained acquisition of stimulus function is one of the most interesting findings to emerge from the recent and growing body of research on stimulus classes, and it is the primary topic of this chapter.

Circadian rhythms in electric waveform structure and rate in the electric fish Brachyhypopomus pinnicaudatus

Weakly electric fish have long been known to express day-night oscillations in their discharge rates, and in the amplitude and duration of individual electric organ discharges (EODs). Because these oscillations are altered by social environment and neuroendocrine interactions, electric fish are excellent organisms for exploring the social and neuroendocrine regulation of circadian rhythm expression. Previous studies asserting that these oscillations are circadian rhythms have been criticized for failing to control temperature and randomize feeding regimes, or for running the fish under constant conditions for just 2-3 days. Here we show that the day-night oscillations in the EODs of the neotropical gymnotiform fish Brachyhypopomus pinnicaudatus free-run for over a week under constant photic and thermal conditions, and randomized food provisioning. Sex differences were apparent in strength and magnitude of the circadian oscillations; male oscillations were stronger and larger. All three parameters retain a common oscillation period while differing in the persistence of oscillation strength and magnitude, a difference consistent with proposals by others that declines of behavioral circadian rhythms may result from breakdowns downstream of the central oscillator.

Emergence of Conditional Stimulus Relations and Transfer of Respondent Eliciting Functions Among Compound Stimuli

Previous research has demonstrated that conditioned elicitation functions can transfer via stimulus equivalence classes. However, thus far investigations in this area have been limited to stimulus equivalence classes involving single element stimuli. This study attempted to demonstrate the transfer of eliciting functions via emergent relations involving compound stimuli. Eight college students participated in this study. Six of these participated in all experimental procedures, while the remaining two served as controls and did not receive some phases of the experiment. The experimental participants were first taught nine conditional relations of compound stimuli and unitary stimuli (AC-B & BC-A) using match-to-sample training. They were then tested for the emergence of untrained relations involving different combinations of the previously learne9 compound-single element relations and compound-compound relations (AC-AC or AB-AB or BC-BC). A classical conditioning procedure was then performed in which one compound stimulus from one class was paired with mild electric shock (1.0-2.0 mA) while two other compounds from two different classes were presented in the absence of shock. Participants were then presented with other compounds from the appropriate classes to assess whether the eliciting function had transferred to stimuli which were members of the same class as the originally conditioned stimulus. The control participants received the same procedures except for the initial conditional discrimination training of the compound-single relations and the testing for the emergence of compound-single relations. Four of thoe six experimental participants demonstrated transfer of the eliciting function. An analysis of the performance of both of the individuals who failed to demonstrate the transfer revealed that they may have failed to ° maintain the classes throughout the experiment. One participant discontinued the experiment before further procedures

Signal Cloaking by Electric Fish

ABSTRACT Electric fish produce weak electric fields to image their world in darkness and to communicate with potential mates and rivals. Eavesdropping by electroreceptive predators exerts selective pressure on electric fish to shift their signals into less-detectable high-frequency spectral ranges. Hypopomid electric fish evolved a signal-cloaking strategy that reduces their detectability by predators in the lab (and thus presumably their risk of predation in the field). These fish produce broad-frequency electric fields close to the body, but the heterogeneous local fields merge over space to cancel the low-frequency spectrum at a distance. Mature males dynamically regulate this cloaking mechanism to enhance or suppress low-frequency energy. The mechanism underlying electric-field cloaking involves electrogenic cells that produce two independent action potentials. In a unique twist, these cells orient sodium and potassium currents in the same direction, potentially boosting their capabilities for current generation. Exploration of such evolutionary inventions could aid the design of biogenerators to power implantable medical devices, an ambition that would benefit from the complete genome sequence of a gymnotiform fish.

Transfer of Operant Discrimination and Respondent Elicitation via Emergent Relations of Compound Stimuli

Two experiments investigated transfer of stimulus functions via emergent relations of compound stimuli. In Experiment 1, 4 college students were taught nine conditional relations of compound stimuli and unitary stimuli (A1B1-C1, A1B2-C3, A1B3-C2, A2B1-C3, A2B2-C2, A2B3-C1, A3B1-C2, A3B2-C1, and A3B3-C3), then tested for 18 untrained stimulus relations derived from the trained relations (e.g., A1C1-B1; B1C1-A1). Participants were then taught to sequence the A stimuli (A1 →A2→A3), and tested for transfer of this sequencing response to BC compounds. Two participants demonstrated transfer of the sequencing response. Two participants demonstrated transfer of the sequencing response after additional experimental phases. In Experiment 2, 5 college students were taught nine AB-C relations and then tested for 18 AC-B and BC-A relations as in Experiment 1. A skin conductance response was conditioned to A1 by pairing this stimulus with mild electric shock. Participants were then tested for transfer of this skin conductance response to B1C1 and B3C2. Three participants showed the transfer of conditioning. One participant did not demonstrate conditioning of the skin conductance response. One participant showed transfer of the skin conductance response after a supplemental conditioning phase. Initial failures to show transfer for some participants suggest that transfer of function sometimes depends upon a history of differential responding to compound stimuli. These results suggest that emergent relations involving compound stimuli and stimulus equivalence are related phenomena.