Molecular Separation of Two Behavioral Phenotypes by a Mutation Affecting the Promoters of a Ca-Activated K Channel

Atkinson, Nigel S.; Brenner, Robert; Chang, Whei Meih; Wilbur, Jennette L.; Larimer, James L.; Yu, Jialiang

doi:10.1523/jneurosci.20-08-02988.2000

Cited by 46 publications

(60 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This observation is further supported by the analysis of ash2 18 /ϩ flies carrying a lethal inversion that exclusively removes the neural promoters away from the slo locus, leaving the remaining intact (33). This inversion has been shown to complement only the muscle-associated defects of slo 4 (28). Fig.…”

Section: Resultsmentioning

confidence: 69%

“…A null mutation in the slo locus strikingly alters the electrical properties of both neurons and muscles (22)(23)(24), affecting neurotransmitter release (25) and thereby causing a variety of behavioral defects among those in courtship behavior (26)(27)(28). We have previously demonstrated that a slo null mutant is behaviorally arrhythmic under free-running [constant darkness (DD)] conditions (13).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Impaired clock output by altered connectivity in the circadian network

Fernández

Chu

Villella

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Substantial progress has been made in elucidating the molecular processes that impart a temporal control to physiology and behavior in most eukaryotes. In Drosophila, dorsal and ventral neuronal networks act in concert to convey rhythmicity. Recently, the hierarchical organization among the different circadian clusters has been addressed, but how molecular oscillations translate into rhythmic behavior remains unclear. The small ventral lateral neurons can synchronize certain dorsal oscillators likely through the release of pigment dispersing factor (PDF), a neuropeptide central to the control of rhythmic rest-activity cycles. In the present study, we have taken advantage of flies exhibiting a distinctive arrhythmic phenotype due to mutation of the potassium channel slowpoke (slo) to examine the relevance of specific neuronal populations involved in the circadian control of behavior. We show that altered neuronal function associated with the null mutation specifically impaired PDF accumulation in the dorsal protocerebrum and, in turn, desynchronized molecular oscillations in the dorsal clusters. However, molecular oscillations in the small ventral lateral neurons are properly running in the null mutant, indicating that slo is acting downstream of these core pacemaker cells, most likely in the output pathway. Surprisingly, disrupted PDF signaling by slo dysfunction directly affects the structure of the underlying circuit. Our observations demonstrate that subtle structural changes within the circadian network are responsible for behavioral arrhythmicity.circadian circuitry ͉ Drosophila ͉ pigment dispersing factor ͉ potassium channels ͉ slowpoke R hythmicity in rest-activity cycles in Drosophila is under control of the circadian clock, which is based on selfsustaining, cell-autonomous transcriptional negative feedback loops. These feedback loops ultimately give rise to rhythms in the abundance, phosphorylation state, and nuclear localization of key intracellular proteins, such as period (PER) and timeless (TIM) (1). To date, several neuronal clusters have been shown to include a molecular oscillator. The one best understood encompasses the small ventral lateral neurons (LNvs), comprised of five cells, of which four rhythmically release the neuropeptide pigment dispersing factor (PDF) at their dorsal terminals. Other oscillators within the fly brain include the dorsal lateral neurons (LNds) together with the dorsal neurons (DN1-3) (2). Ablation of all LNvs by overexpression of proapoptotic genes, as well as null mutations on the pdf gene or its receptor, cause behavioral arrhythmicity a few days upon transfer to constant conditions (3-6) likely through the gradual loss of synchronization among the components of the small LNv cluster (7).The question of how the intracellular molecular oscillations taking place within specific neuronal clusters ultimately drive rhythmic locomotor activity has only recently been approached in Drosophila (7-11). Molecular oscillations must be somehow transduced into neuronal function to...

show abstract

Section: Resultsmentioning

confidence: 69%

mentioning

confidence: 99%

Impaired clock output by altered connectivity in the circadian network

Fernández

Chu

Villella

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…In particular, differential expression of alternatively spliced BK type Ca 2+ -activated K + channels are known to be of physiological importance (i.e. Atkinson et al, 2000;Rosenblatt et al, 1997), and an interesting hypothesis is that differential expression of a specific SLO-1 isoform in M4, in the Rhabditidae family, is critical for inactivating M4-TB synapses.…”

Section: Discussionmentioning

confidence: 99%

Evolution of pharyngeal behaviors and neuronal functions in free-living soil nematodes

Chiang

Steciuk

Shtonda

et al. 2006

Journal of Experimental Biology

View full text Add to dashboard Cite

SUMMARY To explore the use of Caenorhabditis elegans and related nematodes for studying behavioral evolution, we conducted a comparative study of pharyngeal behaviors and neuronal regulation in free-living soil nematodes. The pharynx is divided into three parts: corpus, isthmus and terminal bulb,and pharyngeal behaviors consist of stereotyped patterns of two motions:pumping and peristalsis. Based on an outgroup species, Teratocephalus lirellus, the ancestral pattern of pharyngeal behaviors consisted of corpus pumping, isthmus peristalsis and terminal bulb pumping, each occurring independently. Whereas corpus pumping remained largely conserved, isthmus and terminal bulb behaviors evolved extensively from the ancestral pattern in the four major free-living soil nematode families. In the Rhabditidae family,which includes Caenorhabditis elegans, the anterior isthmus switched from peristalsis to pumping, and anterior isthmus and terminal bulb pumping became coupled to corpus pumping. In the Diplogasteridae family, the terminal bulb switched from pumping to peristalsis, and isthmus and terminal bulb became coupled for peristalsis. In the Cephalobidae family, isthmus peristalsis and terminal bulb pumping became coupled. And in the Panagrolaimidae family, the posterior isthmus switched from peristalsis to pumping. Along with these behavioral changes, we also found differences in the neuronal regulation of isthmus and terminal bulb behaviors. M2, a neuron that has no detectable function in C. elegans, stimulated anterior isthmus peristalsis in the Panagrolaimidae. Further, M4 was an important excitatory neuron in each family, but its exact downstream function varied between stimulation of posterior isthmus peristalsis in the Rhabditidae,isthmus/terminal bulb peristalsis in the Diplogasteridae, isthmus peristalsis and terminal bulb pumping in the Cephalobidae, and posterior isthmus/terminal bulb pumping in the Panagrolaimidae. In the Rhabditidae family, although M4 normally has no effect on the terminal bulb, we found that M4 can stimulate the terminal bulb in C. elegans if the Ca2+-activated K+ channel SLO-1 is inactivated. C. elegans slo-1 mutants have generally increased neurotransmission, and in slo-1 mutants we found novel electropharyngeogram signals and increased pumping rates that suggested activation of M4-terminal bulb synapses. Thus, we suggest that the lack of M4-terminal bulb stimulations in C. elegans and the Rhabditidae family evolved by changes in synaptic transmission. Altogether, we found behavioral and neuronal differences in the isthmus and terminal bulb of free-living soil nematodes, and we examined potential underlying mechanisms of one aspect of M4 evolution. Our results suggest the utility of Caenorhabditis elegans and related nematodes for studying behavioral evolution.

show abstract

“…Distinct transcripts can shape the channel properties to the requirements of the cells, tissue, developmental stage or physiological state. In Drosophila, tissue-specific transcriptional promoters (Atkinson et al, 2000;Brenner et al, 1996) and alternative splicing (Adelman et al, 1992;Derst et al, 2003;Lagrutta et al, 1994) generate a large number of transcripts that could modify channel properties such as singlechannel conductance, calcium sensitivity and mean open time (Adelman et al, 1992;Lagrutta et al, 1994). In vertebrates, alternatively spliced BK transcripts are expressed in distinct patterns in the brain (Tseng-Crank et al, 1994), cochlea (Jiang et al, 1997;Langer et al, 2003), kidney (Bravo-Zehnder et al, 2000) and smooth muscle of arteries, esophagus and uterus (Knaus et al, 1994;Salapatek et al, 2002;Zhou et al, 2000), suggesting isoform-specific functions.…”

mentioning

confidence: 99%

Calcium-activated potassium channel of the tobacco hornworm,Manduca sexta: molecular characterization and expression analysis

Keyser

Witten

2005

Journal of Experimental Biology

View full text Add to dashboard Cite

Large-conductance calciumand voltage-gated potassium channels (BK or Slowpoke) serve as dynamic integrators linking electrical signaling and intracellular activity. These channels can mediate many different Ca 2+ -dependent physiological processes including the regulation of neuronal and neuroendocrine cell excitability and muscle contraction. To gain insights into the function of BK channels in vivo, we isolated a full-length cDNA encoding the alpha subunit of a Slowpoke channel from the tobacco hornworm, Manduca sexta (msslo). Amino acid sequence comparison of the deduced Manduca protein revealed at least 80% identity to the insect Slo channels. The five C-terminal alternative splice regions are conserved, but the cloned cDNA fragments contained some unique combinations of exons E, G and I. Our spatial profile revealed that transcript levels were highest in skeletal muscle when compared with the central nervous system (CNS) and visceral muscle. The temporal profile suggested that msslo expression is regulated developmentally in a tissue-and regional-specific pattern. The levels of msslo transcripts remain relatively constant throughout metamorphosis in the CNS, transiently decline in the heart and are barely detectable in the gut except in adults. A dramatic upregulation of msslo transcript levels occurs in thoracic but not abdominal dorsal longitudinal body wall muscles (DLM), suggesting that the msSlo current plays an important role in the excitation or contractile properties of the phasic flight muscle. Our developmental profile of msslo expression suggests that msSlo currents may contribute to the changes in neural circuits and muscle properties that produce stage-specific functions and behaviors.

show abstract

Molecular Separation of Two Behavioral Phenotypes by a Mutation Affecting the Promoters of a Ca-Activated K Channel

Cited by 46 publications

References 31 publications

Impaired clock output by altered connectivity in the circadian network

Impaired clock output by altered connectivity in the circadian network

Evolution of pharyngeal behaviors and neuronal functions in free-living soil nematodes

Calcium-activated potassium channel of the tobacco hornworm,Manduca sexta: molecular characterization and expression analysis

Contact Info

Product

Resources

About