Beyond the Paper: A Conversation with Soraya Meftah, Max Wilson, and Sam Booker

Interviewed by Dr. Paige N. McKeon, March 12, 2026

In a study preregistered with eNeuro, Drs. Max Wilson, Soraya Meftah and Sam Booker explored whether amyloid-β, a protein that accumulates during Alzheimer’s disease, damages inhibitory synapses expressing GABA_B receptors. Using an electrophysiological and biochemical approach on an Alzheimer’s disease mouse model, the authors discovered that amyloid-β accumulation may not affect GABA_B expression but does influence pre- and postsynaptic GABA_B signaling.

“I had never preregistered a study before this paper. I would say the process was largely equivalent in terms of time and energy to a more typical publication (i.e., research first, write up later), but the confidence in the method is much higher. The preregistration process gives me much greater confidence in our findings. We went in with a very clear hypothesis guided by previously published studies from several labs—which all lacked functional validation.” —Sam Booker

Drs. Max Wilson (left), Soraya Meftah (center), and Sam Booker (right).

Please share your personal research journeys. How have your experiences led you to where you are now?

SM: I began my research journey during my undergraduate degree, where I had the opportunity to spend a year in Lyon, France, researching sleep and sleep disorders. This included performing EEG recordings and behavior experiments, assessing the impact of sleep deprivation in a mouse model of narcolepsy. This really opened my eyes to a career as a researcher, giving me a taste of what day-to-day life is like.

Following my degree, I was employed at Eli Lilly for three years as a Molecular Pathologist. This gave me a real passion for neurodegenerative research, and an appreciation of preclinical drug discovery. During this time, I found myself wanting to further explore research questions in more depth beyond my work projects remit. I also wanted to advance my research career, deepen my foundation in neuroscience research, and expand my technical skillset beyond histology—my main technical skillset at the time. Therefore, I moved to the University of Exeter to undertake my PhD with Drs. Jonathan Brown, Jonathan Witton, and Michael Ashby, to explore synaptic dysfunction in a mouse model of tauopathy.

During this time, I was really given the freedom and independence to explore my research whichever direction it went. This led to me applying for a small grant to learn in vivo whole-cell patch-clamp electrophysiology from Drs. Jean-Sebastien Jouhanneau and James Poulet in Berlin. I was then able to apply this technique to my research questions, where I observed dysfunction in synaptic integration and temporal fidelity in our model of tauopathy.

Towards the end of my PhD, I was looking for postdoctoral positions where I could apply the skills I had developed during my PhD and ended up joining the group of Dr. Jian Gan at the University of Edinburgh. Here I was able to apply and develop my in vivo electrophysiology skillset, performing blind in vivo whole-cell patch-clamp recordings in the hippocampus.

After a few years, I joined the group of Dr. Claire Durrant, as I wanted to work on nonrodent models, and within this group we developed a living human brain-slice culture model to study diseases that cause dementia. Finally, I have just been awarded an Alzheimer’s Research United Kingdom-Research Against Dementia (ARUK-RAD) fellowship to start my own lab, where I aim to investigate mechanisms of hyperactivity and potential ways to rescue this in Alzheimer’s disease.

MW: When I was 16, I was fortunate to be part of the Nuffield Research Placement scheme, which gave me my first taste of real laboratory work. I joined Dr. Sonia Rocha and her team at the University of Dundee, investigating hypoxia and transcription factors, an interesting topic that unfortunately went entirely over my head at the time. But I was taught how to carry out western blots on cell culture samples, and the experience was eye-opening. That placement planted a seed that shaped my entire career—it showed me how exciting science could be and that it was a path worth pursuing.

SB: I took part in a now (sadly) defunct junior science competition when I was 9 or 10 with one of my best friends at primary school in semirural Australia supervised by my father. We (the kids) measured the proportion of waste going to landfill versus recycling and compared to local and national averages—often rummaging through bins and weighing various bags in the rain while riding from house to house on our bikes. It gave me a very early insight into the hard work, enthusiasm, and perseverance needed to pursue a career in research and an attitude to do what you want your own way. Since then, I have tried to combine those attributes with genuine curiosity, friendliness, and compassion through all my subsequent endeavors.

“For those considering embarking on the path to research independence, the only advice I can give is to love what you study and be proud of who you study it with.” —Sam Booker

Dr. Booker, what was it like setting up your lab?

SB: I was extremely fortunate in many ways to be afforded the opportunity to start my own lab in the department where I had worked for my second postdoctoral position. This gave me a big headstart in terms of understanding the local procedures and politics.

However, the main challenge was moving out from the shadow of my former supervisors (who are all very successful in their own rights). This was challenging and, at times, extremely frustrating, but now 4–5 years after starting my group, I think we have struck a good balance of collaboration with former mentors and independent work.

The main support I have utilized is the time and patience of colleagues of all career stages to discuss and collaborate to forge new and exciting research avenues. Before starting my team, I wish I knew how much extra effort it is to worry about the careers and successes of all your team members past and present alongside your own.

What keeps you motivated? What advice do you have for those interested in similar career trajectories?

SM: I’m not really too sure...There are definitely some days where I do not feel motivated! I think we’re lucky as scientists to be working on the cusp of novelty, constantly learning and having to problem solve, and while this is exciting, it can also be extremely frustrating. I enjoy having this variety, and I really think that we are progressing in research toward cures for diseases that cause dementia, which helps keep me motivated.

As a person, I am also very stubborn, which I think can also help with motivation and I don’t like to give up on things very easily. There are always times where you can lose sight of what progress you are making and lose motivation. In these scenarios, I like to take a step back and acknowledge what progress has been made. If I could give any advice, it would be to keep turning up day after day. Research is a marathon, not a sprint. I would also try not to put too much pressure and self-worth into your data and results so that you can be happy regardless of whether what you find is positive or negative statistically.

“I think we’re lucky as scientists to be working on the cusp of novelty, constantly learning and having to problem solve, and while this is exciting it can also be extremely frustrating. I enjoy having this variety, and I really think that we are progressing in research toward cures for diseases that cause dementia, which helps keep me motivated.” —Soraya Meftah

SB: From a personal perspective, a good work–life balance is a great motivator. Perhaps it is a little cliche, but being able to step away from the lab or office for a few hours or days is a great way of gaining perspective. From a group leader perspective, I have tried to foster an ethos of openness coupled with critical thinking in my team. It is truly motivating to see trainees in the lab developing these attributes for themselves and conveying them to others. From a scientific perspective, I am fundamentally enthralled by the current surge of research in human brain tissue. The goal of being able to better understand human neurological disease and identify better treatments that bring substantive benefit to patients has never been closer and this is incredible. For those considering embarking on the path to research independence, the only advice I can give is to love what you study and be proud of who you study it with.

Why did you decide to preregister this study? How would you describe the process to someone who hasn’t done it before?

SB: I had never preregistered a study before this paper. I would say the process was largely equivalent in terms of time and energy to a more typical publication (i.e., research first, write up later), but the confidence in the method is much higher. Overall, the process was incredibly straightforward. We, Dr. Claire Durrant and I, had the idea for this study. I proposed a preregistration and agreed I would draft the stage one manuscript. We then discussed the plan with Drs. Meftah and Wilson, who agreed to contribute.

The main pitfall of our study was the age-dependent nature of the research—with many mice needing to be 6–12 months old, which required considerably planning during preparation of the initial manuscript. Because the experiments were planned and power analysis performed prior to starting, we knew our goalposts and what the reviewers of the stage one manuscript expected as a minimum level of evidence. This meant that preparation of the figures and discussion of the results was extremely straightforward.

Did preregistration increase your confidence in the methodological plan and results?

SB: The preregistration process gives me much greater confidence in our findings. We went in with a very clear hypothesis guided by previously published studies from several labs—which all lacked functional validation. We uniformly failed to reject the null hypothesis, but this in and of itself is of fundamental importance for our understanding of the physiological basis of neurological function. If we add into this, that the process prevented us from “harking” or “p-hacking,” this can only be an added bonus.

Would you recommend that others consider doing a registered report?

SB: I would highly recommend submitting a registered report for all researchers. I don’t believe this approach inhibits serendipitous discovery—as several leads from the work we performed are being followed up by other members of our teams. But it is a great way to formalize a study, ensure reproducibility, and gives a clear pathway to publication. One route I am considering in the future is to encourage postgraduate students to preregister their projects early, thus encouraging open research in research training. This I hope to start to adopt with my current and future PhD students.

Can you talk a little bit about any unforeseen challenges in carrying out the experiments in this paper and how you overcame them?

SB: There were two main challenges for this article that I noted. First, the range of ages and experiment type that we outlined in our stage one manuscript, in hindsight, were perhaps excessive to fail to reject the null hypothesis. Nevertheless, we did not know this from the outset, hence the value of this study. Second, the breadth of data types involved was quite extensive—ranging from cellular, synaptic, and circuit neurophysiology, to neuronal morphology and machine learning approaches, to slice culture and biochemical analysis. We overcame this by involving an array of researchers across the teams involved and including external collaborators and importantly, recruiting short-term project students to help with data collection and analysis. Without this team effort, this would not have been possible.

This study ended with null results, which eNeuro welcomes with or without preregistration. Do you think you would have submitted this paper if it were not a registered report?

MW: I would like to think so, but the reality is that many journals are reluctant to publish null results. The preregistration removed that uncertainty entirely; our work was judged on the quality of the research question, not on whether the results were eye-catching. That matters, because when negative data goes unpublished, other researchers waste time and resources asking the same question without knowing it has already been answered.

SB: I would have. I fundamentally believe that negative data is as important as positive. Indeed, we have now published two to three papers from my lab with primarily negative data. It is crucial for trainees that they have a publication record, and it is of no benefit to the field if data sits on a figurative shelf gathering dust, with just a select few knowing of its existence.

“[…] The reality is that many journals are reluctant to publish null results. The preregistration removed that uncertainty entirely; our work was judged on the quality of the research question, not on whether the results were eye-catching. That matters, because when negative data goes unpublished, other researchers waste time and resources asking the same question without knowing it has already been answered.” — Max Wilson

Were you surprised by the results? What new questions arose with these results?

SB: In short…Yes, I was very surprised by our findings. The work on which this study was based was performed by several labs whose approaches are robust and their conclusions well-justified. The outcomes of this work are actively being pursued by members of our team, but by using cell- and synapse-specific approaches. A key question arising is how well findings made in biochemical, anatomical, or indeed transcriptomic data sets relate to the fundamental physiology of neurons. This is something that we are really only scratching the surface of and is crucial if we as a field hope to best interpret multifaceted datasets such as these.

Connect with Sam Booker on Bluesky.

Check out this Snapshots in Neuroscience: Neurotoxic Plaques in the Hippocampus featuring an image from their paper. 

Read the full article:

GABA_B Receptor signaling in CA1 Pyramidal Cells is not Regulated by Aging in the APP/PS1 Mouse Model of Amyloid Pathology
Soraya Meftah, Max A. Wilson, Jamie Elliott, Lauren McLay, Vladimirs Dobrovolskis, Samuel Rosencrans, Lewis W. Taylor, Claudia Mugnaini, Rafaela Mostallino, Claire S. Durrant, and Sam A. Booker