ECR Spotlight – Amit Rana

Amit Rana

Describe your scientific journey and your current research focus

My passion for neuroscience has always been burning within me and was further ignited during my time studying at Panjab University under the guidance of Professor Rajat Sandhir. However, it was not until I stumbled upon a TED Talk by Ed Yong about parasitoid wasps and their manipulation of cockroach behavior that my interests took a thrilling turn towards neuro-parasitism. Fate intervened when I discovered the fascinating work of Professor Frederic Libersat on the jewel wasp and zombie cockroaches. Just a brief conversation with Professor Libersat was enough, and I knew that this is where I belonged. In June 2019, I joined his lab for my doctoral studies. Looking back, I know that this was one of the best decisions I have ever made in my life. During my doctorate, I studied the effect of wasp venom on spontaneous as well as evoked neuronal activity. Additionally, I also investigated the effect of venom on desensitizing the nociceptive behavior in stung cockroaches.

How would you explain the main finding of your paper to a member of the public?

In this study, we shed new light on the effects of a venomous sting delivered by the jewel wasp, Ampulex compressa. The venom is known to induce a specific behavioral sequence in cockroaches that includes grooming and the absence of spontaneous movement (hypokinesia). Through the use of chronic recordings, we are able to provide a neural basis for this venom-induced hypokinesia.

Our study revealed that hypokinesia correlates with an overall reduction in neuronal activity in a specific area of the cockroach brain, known as the central complex (CX). We employed, for the first time, chronic recordings of patterned cockroach CX activity in real time as the brain is infused with wasp venom. CX envenomation is followed by sequential changes in the pattern of neuronal firing that can be divided into three distinct temporal phases during the two-hour interval post-venom injection: (1) reduction in neuronal activity for roughly 10 min immediately after venom injection; (2) rebound of activity lasting up to 25 min; (3) reduction of ongoing activity for up to 2 h. Long-term reduction of CX activity after venom injection is accompanied by decreased activity of both descending interneurons projecting to thoracic locomotory circuitry (DINs) and motor output. Our findings in this study help to unravel the cascade of events occurring in cockroach head ganglia after wasp venom injection. The first potential weapon deployed by the wasp is presumably GABA, a neurotransmitter, which reduces neuronal activity of the CX sharply, though briefly. As the actions of GABA wear off, dopamine, another neurotransmitter, present in the wasp venom triggers intense and prolonged grooming. Subsequently, the other proteins and peptides in the venom suppress neuronal activity in the CX, leading to reduced DIN influences on thoracic ganglia circuitry. Diminished activity of thoracic ganglia reduces the excitability of both Ds and Df motoneurons, ultimately leading to suppressed spontaneous walking and onset of hypokinesia.

Overall, this study provides new insights into the complex neural mechanisms underlying the venom-induced hypokinesia in cockroaches, and highlights the potential of this venom as a tool for studying the neural basis of behavior.

What are the potential implications of this finding for your field of research, and is there anything that you learned during this study that you wish you had known sooner?

The results of this study provide a unique opportunity to delve deeper into the specific relationships between venom components and their molecular targets, ultimately leading to a more comprehensive understanding of how manipulation of the central complex activity affects motor control. Additionally, the diverse effects of wasp venom across multiple stages, as identified both behaviorally and physiologically, provide a valuable tool for investigating synaptic circuits and uncovering potential therapeutic and pharmaceutical properties of venom components.

Which part of this research project was the most rewarding/challenging?

The experiments conducted in this study presented their own set of challenges, but none were as challenging as recording the activity of the central complex while simultaneously injecting venom/saline into the same region. The cerebral ganglia is small and highly plastic, making it crucial to use the correct diameter of nanoinjector capillary. A capillary that was too small would become clogged within the brain, while a capillary that was too large would cause excessive movement of the brain. Despite these obstacles, I was able to successfully perform the injections without losing neuronal recording, even if it meant staying late in the lab for extended periods of time during my PhD. It was also the most rewarding part, as looking at those units isolated from the neuronal recording was truly satisfying.

Are there any important historical papers from your field that have been published in JEB? If so, which paper, and how did it pave the way for later research?

‘The central nervous control of flight in a locust’ by D. M. Wilson (1961) (doi:10.1242/jeb.38.2.471). This classic article shows that the complete motor pattern of locust flight could be generated by fully deafferented thoracic ganglia, despite being unable to receive the inputs required by the proprioceptive chain model. The paper proved that basic coordination of flight is an inherent function of central nervous system and proprioceptive feedback only corrects this predefined motor pattern from any deviation and thus provided the foundation for the idea of dedicated central pattern generators to perform specific motor task.

What do you think experimental biology will look like 50 years from now?

I am confident that in the next 50 years, experimental biology will continue to evolve and advance, driven by the integration of computational and bioinformatics approaches. The use of machine learning and artificial intelligence techniques will become a crucial component in experimental biology research. These developments will not only aid in addressing issues related to climate change and sustainable growth, but also lead to a deeper understanding of ethical and societal concerns through comparative studies using diverse animal models.

If you had unlimited funding, what question in your research field would you most like to address?

If I had an unlimited budget, I would look into the therapeutic potential of wasp venom. I am confident that this will lead to the discovery of new and exciting opportunities. We know that wasp venom is made up of a diverse mixture of over 250 peptides, many of which are still unknown. However, I believe that with focused attention and research, we can identify specific venom peptides with the potential to be developed into powerful new drugs for conditions such as epilepsy and arrhythmia.

What changes do you think could improve the lives of early-career researchers, and what would make you want to continue in a research career?

I am optimistic that by increasing funding opportunities for early-career researchers (ECRs), providing more clearly defined work hours, reducing bureaucratic barriers, and accepting negative results as valuable contributions, we can create a better environment for ECRs to thrive in their research and improve their overall well-being. This will lead to more productive and effective research, and ultimately, advancements in our field.