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Harold H Zakon

Publications and source records attributed to Harold H Zakon.

11 recordsLinked to original sources
PubMed2006

Gene duplications and evolution of vertebrate voltage-gated sodium channels.

Voltage-gated sodium channels underlie action potential generation in excitable tissue. To establish the evolutionary mechanisms that shaped the vertebrate sodium channel alpha-subunit (SCNA) gene family and their encoded Nav1 proteins, we identified all SCNA genes in several teleost species. Molecular cloning revealed that teleosts have eight SCNA genes, compared to ten in another vertebrate lineage, mammals. Prior phylogenetic analyses have indicated that the genomes of both teleosts and tetrapods contain four monophyletic groups of SCNA genes, and that tandem duplications expanded the number of genes in two of the four mammalian groups. However, the number of genes in each group varies between teleosts and tetrapods, suggesting different evolutionary histories in the two vertebrate lineages. Our findings from phylogenetic analysis and chromosomal mapping of Danio rerio genes indicate that tandem duplications are an unlikely mechanism for generation of the extant teleost SCNA genes. Instead, analyses of other closely mapped genes in D. rerio as well as of SCNA genes from several teleost species all support the hypothesis that a whole-genome duplication was involved in expansion of the SCNA gene family in teleosts. Interestingly, despite their different evolutionary histories, mRNA analyses demonstrated a conservation of expression patterns for SCNA orthologues in teleosts and tetrapods, suggesting functional conservation.

Animals↗
PubMed2006

Sodium channel genes and the evolution of diversity in communication signals of electric fishes: convergent molecular evolution.

We investigated whether the evolution of electric organs and electric signal diversity in two independently evolved lineages of electric fishes was accompanied by convergent changes on the molecular level. We found that a sodium channel gene (Na(v)1.4a) that is expressed in muscle in nonelectric fishes has lost its expression in muscle and is expressed instead in the evolutionarily novel electric organ in both lineages of electric fishes. This gene appears to be evolving under positive selection in both lineages, facilitated by its restricted expression in the electric organ. This view is reinforced by the lack of evidence for selection on this gene in one electric species in which expression of this gene is retained in muscle. Amino acid replacements occur convergently in domains that influence channel inactivation, a key trait for shaping electric communication signals. Some amino acid replacements occur at or adjacent to sites at which disease-causing mutations have been mapped in human sodium channel genes, emphasizing that these replacements occur in functionally important domains. Selection appears to have acted on the final step in channel inactivation, but complementarily on the inactivation "ball" in one lineage, and its receptor site in the other lineage. Thus, changes in the expression and sequence of the same gene are associated with the independent evolution of signal complexity.

Amino Acid Sequence↗
PubMed2006

A "sample-and-hold" pulse-counting integrator as a mechanism for graded memory underlying sensorimotor adaptation.

The mechanisms behind the induction of cellular correlates of memory by sensory input and their contribution to meaningful behavioral changes are largely unknown. We previously reported a graded memory in the form of sensorimotor adaptation in the electromotor output of electric fish. Here we show that the mechanism for this adaptation is a synaptically induced long-lasting shift in intrinsic neuronal excitability. This mechanism rapidly integrates hundreds of spikes in a second, or gradually integrates the same number of spikes delivered over tens of minutes. Thus, this mechanism appears immune to frequency-dependent fluctuations in input and operates as a simple pulse counter over a wide range of time scales, enabling it to transduce graded sensory information into a graded memory and a corresponding change in the behavioral output. This adaptation is based on an NMDA receptor-mediated change in intrinsic excitability of the postsynaptic neurons involving the Ca2+-dependent activation of TRP channels.

Acclimatization↗
PubMed2006

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.

Action Potentials↗
PubMed2005

Species-specific differences in sensorimotor adaptation are correlated with differences in social structure.

Here, we report a species difference in the strength and duration of long-term sensorimotor adaptation in the electromotor output of weakly electric fish. The adaptation is produced by changes in intrinsic excitability in the electromotor pacemaker nucleus; this change is a form of memory that correlates with social structure. A weakly electric fish may be jammed by a similar electric organ discharge (EOD) frequency of another fish and prevents jamming by transiently raising its own emission frequency, a behavior called the jamming avoidance response (JAR). The JAR requires activation of NMDA receptors, and prolonged JAR performance results in long-term frequency elevation (LTFE) of a fish's EOD frequency for many hours after the jamming stimulus. We find that LTFE is stronger in a shoaling species (Eigenmannia virescens) with a higher probability of encountering jamming conspecifics, when compared to a solitary species (Apteronotus leptorhynchus). Additionally, LTFE persists in Eigenmannia, whereas, it decays over 5-9 h in Apteronotus.

Acclimatization↗
PubMed2005

Sonic and electric fish: at the crossroads of neuroethology and behavioral neuroendocrinology.

Field and laboratory studies of weakly electric and sound-producing teleost fishes demonstrate how steroidal and non-steroidal hormones mediate the translation of neural events into behavior. The development of this research program has depended upon an interdisciplinary neuroethological approach that has characterized the neurophysiological properties of the motor and sensory pathways that lead to the production and detection of easily quantified highly stereotyped behaviors, namely, electric organ discharges (EODs) and vocalizations. Neuroethological studies of these teleosts have now integrated a behavioral neuroendocrinology approach that has provided several examples of how hormone-sensitive neurobiological traits contribute to adaptive behavioral plasticity in natural habitats. As such, these studies provide guideposts for comparable studies in other groups of teleosts and vertebrates in general.

Androgens↗
PubMed2003

Insight into the mechanisms of neuronal processing from electric fish.

Weakly electric fish use their electric fields to locate objects and communicate with each other. Their electric discharges vary with species, gender, and social status. This variation is mediated by steroid and peptide hormones that influence ion currents through changes in gene expression or phosphorylation state. Understanding how electric fish decode the perturbations of their electric fields that result from interactions with the discharges of other fish or prey is illuminating general mechanisms of neuronal processing. Their central sensory circuits are specialized to process amplitude modulated signals, to detect microsecond variations in spike timing, and are dynamically reconfigured depending on the stimulus parameters.

Animal Communication↗
PubMed2002

Skeletal muscle transformation into electric organ in S. macrurus depends on innervation.

The cells of the electric organ, called electrocytes, of the weakly electric fish Sternopygus macrurus derive from the fusion of mature fast muscle fibers that subsequently disassemble and downregulate their sarcomeric components. Previously, we showed a reversal of the differentiated state of electrocytes to that of their muscle fiber precursors when neural input is eliminated. The dependence of the mature electrocyte phenotype on neural input led us to test the hypothesis that innervation is also critical during formation of electrocytes. We used immunohistochemical analyses to examine the regeneration of skeletal muscle and electric organ in the presence or absence of innervation. We found that blastema formation is a nerve-dependent process because regeneration was minimal when tail amputation and denervation were performed at the same time. Denervation at the onset of myogenesis resulted in the differentiation of both fast and slow muscle fibers. These were fewer in number, but in a spatial distribution similar to controls. However, in the absence of innervation, fast muscle fibers did not progress beyond the formation of closely apposed clusters, suggesting that innervation is required for their fusion and subsequent transdifferentiation into electrocytes. This study contributes further to our knowledge of the influence of innervation on cell differentiation in the myogenic lineage.

Animals↗
PubMed2002

The long-term resetting of a brainstem pacemaker nucleus by synaptic input: a model for sensorimotor adaptation.

The cellular mechanisms behind sensorimotor adaptations, such as the adaptation to a sustained change in visual inputs by prism goggles in humans, are not known. Here we present a novel example of long-term sensorimotor adaptation in a well known neuroethological model, the jamming-avoidance response of a weakly electric fish. The adaptation is relatively long lasting, up to 9 hr in vivo, and is likely to be mediated by NMDA receptors. We demonstrate in a brain slice preparation that the pacemaker nucleus is the locus of adaptation and that it responds to long-lasting synaptic stimulation with an increase in the postsynaptic spike frequency persisting for hours after stimulus termination. The mechanism for the neuronal memory behaves as an integrator, and memory duration and strength are quantitatively related to the estimated amount of synaptic stimulation. This finding is contrary to the idea that neurons respond solely to long-lasting synaptic input by turning down their intrinsic excitability. We show that this positive feedback at the cellular level actually contributes to a negative feedback loop at the organismic level if the entire neural circuit and the behavioral link are considered.

Action Potentials↗
PubMed2002

Convergent evolution on the molecular level.

Divergence and convergence are two evolutionary processes by which organisms become adapted to their environments. With the advent of molecular biological techniques it is possible to ask if these processes are observed at the molecular level. There are many examples of molecular divergence in which molecular sequence or function change over evolutionary time. There are fewer reports of convergent evolution on the molecular level, and these claims are sometimes controversial. In this paper I discuss the types of convergent molecular evolution, describe the criteria for accepting or rejecting convergence, and give some examples relevant to neurobiology where convergence has been claimed. These include convergent evolution of opsins, gap junction proteins, neurotransmitter receptors, ion channels, and venoms directed against ion channels.

Animals↗