Travelling in reverse – new insights into how genes and environment control an organism’s exploration of its environment
22 May 2018
By Dr. Kavita Babu, Intermediate Fellow
The human brain has billions of neurons that are interconnected in a complex network. Connection between two neurons is called a ‘synapse’. Many molecules present at the synapse ensure that these connections remain stable. Any dysfunction at the synapse can give rise to a host of neurological disorders such as autism, dementia, addiction etc. Some of these molecules inside the neurons that regulate activation and inhibition of these neurons are called neurotransmitters. Apart from neurotransmitters a set of small peptides (small chain of amino acids) are also known to allow for activation and inhibition of neurons largely via downstream signaling through cell surface proteins called G-protein coupled receptors (GPCRs). These peptides are called neuropeptides and the functioning of these peptides is still fairly unclear. In our lab, we are interested in studying how these peptides work so as to get a better understanding of the workings of neurons and consequently, our brain.
In a recently published study from our group, we used the free-living soil nematode or worm, Caenorhabditis elegans (C.elegans), to understand how a single neuropeptide, FLP-18, functions through two sets of receptors to inhibit activity in a single neuron. C.elegans have long been used by scientists to study human biology as this organism possesses key biological features, including a nervous system, similar to humans. C.elegans, unlike humans who can quickly turn clock-wise or anti-clock-wise, travel in reverse when they need to make a turn. These movements are critical for worm’s survival – whether it is to search for food or to move away from potential predators.
Our research shows that the neuropeptide FLP-18, functions through two GPCR receptors, NPR-4 which is functional on the FLP-18 expressing neuron AVA (giving rise to a feedback of activation and inhibition of the same neuron) and NPR-1 which is expressed on a subset of sensory neurons. Through the activity of these two receptors FLP-18 is able to inhibit the activity of the AVA neuron, which in turn allows for the worm to stop making a reversal or backward motion. The absence of either flp-18 or its receptors’ shows increase in the activity of the AVA neuron and a corresponding increase in the length of the reversals in C. elegans.
We further show that in the absence of food the worm shows increased levels of FLP-18 and a corresponding decrease in the reversal length. Our hypothesis is that with shorter reversals, worms are able to turn and change directions more quickly in their search for food – they conserve energy under starvation conditions. Our data is illustrated in the published model shown below (Bhardwaj et al., 2018).
FLP-18 Functions through the G-Protein-Coupled Receptors NPR-1 and NPR-4 to Modulate Reversal Length in Caenorhabditis elegans. Bhardwaj, A., Thapliyal, S., Dahiya, Y., and Babu, K. The Journal of Neuroscience. May 2018
Banner image credit: Vina Tikiyani. Description: Anterior half of the C.elegans showing neurons markerd with Green Fluorescent Protein (GFP)