Biology subjects

VijayRaghavan, K.

Publications and source records attributed to VijayRaghavan, K..

3 recordsLinked to original sources

bioRxiv2018

A cost effective high-resolution climbing assay applied to Drosophila Parkinson’s and proprioception mutants reveal novel behavioural phenotypes

Severe locomotor impairment is a common phenotype of neurodegenerative disorders such as Parkinsons disease (PD). Drosophila models of PD, studied from more than a decade, have helped in understanding the interaction between various genetic factors, such as parkin and PINK1, in this disease. To characterize locomotor behavioural phenotypes for these genes, fly climbing assays have been widely used. While these simple current assays for locomotor defects in Drosophila mutants measure some locomotor phenotypes well, it is possible that detection of subtle changes in behaviour is important to understand the early manifestation of locomotor disorders. We introduce a novel climbing behaviour assay which provides such fine-scale behavioural data and tests this proposition for the Drosophila model. We use this inexpensive, fully automated, high resolution assay to quantitatively characterize the parameters of climbing behaviour in three contexts. First, we characterize wild type flies and uncover a hitherto unknown sexual dimorphism in climbing behaviour. Second, we study climbing behaviour of heterozygous mutants of genes implicated in the fly PD model and reveal previously unreported prominent locomotor defects in some of these heterozygous fly lines. Finally, we study locomotor defects in a homozygous proprioceptory mutation (Trp-{gamma}1) known to affect fine motor control in Drosophila. Moreover, we identify aberrant geotactic behaviour in Trp-{gamma}1 mutants, thereby opening up a finer assay for geotaxis and its genetic basis. Our assay is therefore a cost-effective, general tool for measuring locomotor behaviours of wild type and mutant flies in fine detail and can reveal mild motor defects.\n\nSignificance statementFine control of neuronal activity is required for proper motor output. Severe locomotor impairment is a common result of neurodegenerative disorders such as Parkinsons disease (PD). The fruitfly, Drosophila, has been widely used as a model system to study the genetics of these disorders and simple climbing assays have been used to study the behavioural phenotypes of mutations in these genes. Here we introduce a novel, fully automated, high resolution climbing behaviour assay and use this assay to characterize climbing behaviour in wild type flies and in various fly mutant lines related to PD and defects in proprioception. Our assay is a general tool for measuring locomotor behaviours of flies in fine detail and can reveal very mild motor defects.

neuroscience↗

bioRxiv2017

GABAergic inhibition of leg motoneurons is required for normal walking behavior in freely moving Drosophila

Walking is a complex rhythmic locomotor behaviour generated by sequential and periodical contraction of muscles essential for coordinated control of movements of legs and leg joints. Studies of walking in vertebrates and invertebrates have revealed that premotor neural circuitry generates a basic rhythmic pattern that is sculpted by sensory feedback and ultimately controls the amplitude and phase of the motor output to leg muscles. However, the identity and functional roles of the premotor interneurons that directly control leg motoneuron activity are poorly understood. Here we take advantage of the powerful genetic methodology available in Drosophila to investigate the role of premotor inhibition in walking by genetically suppressing inhibitory input to leg motoneurons. For this, we have developed a novel algorithm for automated analysis of leg motion to characterize the walking parameters of wildtype flies from high speed video recordings. Further, we use genetic reagents for targeted RNAi knockdown of inhibitory neurotransmitter receptors in leg motoneurons together with quantitative analysis of resulting changes in leg movement parameters in freely walking Drosophila. Our findings indicate that targeted downregulation of GABAA receptor Rdl in leg motoneurons results in a dramatic reduction of walking speed and step-length without the loss of general leg coordination during locomotion. Genetically restricting the knockdown to the adult stage and subsets of motoneurons yields qualitatively identical results. Taken together,these findings identify GABAergic premotor inhibition of motoneurons as an important determinant of correctly coordinated leg movements and speed of walking in freely behaving Drosophila.

neuroscience↗

bioRxiv2017

Identification of single pair of interneurons for bitter taste processing in the Drosophila brain

Drosophila has become an excellent model system for investigating the organization and function of the gustatory system due to the relatively simple neuroanatomical organization of its brain and the availability of powerful genetic and transgenic technology. Thus, at the molecular and cellular level, a great deal of insight into the peripheral detection and coding of gustatory information has already been attained. In contrast, much less is known about the central neural circuits that process this information and induce behaviorally appropriate motor output. Here we combine functional behavioral tests with targeted transgene expression through specific driver lines to identify a single bilaterally homologous pair of bitter sensitive interneurons that are located in the subesophageal zone of the brain. Anatomical and functional data indicate that these interneurons receive specific synaptic input from bitter sensitive gustatory receptor neurons. Targeted transgenic activation and inactivation experiments show that these bitter sensitive interneurons can largely suppress the proboscis extension reflex to appetitive stimuli such as sugar and water. These functional experiments together with calcium-imaging studies indicate that these first order local interneurons play an important role in the inhibition of the proboscis extension reflex that occurs in response to bitter tastants. Taken together, our studies present a cellular identification and functional characterization of a key gustatory interneuron in the bitter sensitive gustatory circuitry of the adult fly.

neuroscience↗