Dr Marie Holt

Supervisor Details

Contact Details

School of Life Sciences, University of Warwick

Scientific Background

Research Interests

Stress is the mind and body’s response to threats, real and imagined, and continued stress can have detrimental effects on our health. Indeed, stress-related disorders, including depression and anxiety, are seen increasingly in our society. At its core, stress is beneficial: In response to stress our body launches a number of coping mechanisms, designed to increase our chances of survival. Our pulse and blood pressure increase and our behaviour changes, including how much we eat. This is normal and useful for us. However, after chronic, unrelenting stress our brains may respond inappropriately, and this can lead to cardiovascular disease and obesity.

My research focusses on how specific brain pathways control the normal healthy response to stress as well as the damaging effects of chronic stress. To do this, we use transgenic mice. Transgenic mice allow us to turn brain cells on and off while monitoring behaviour, pulse, and blood pressure during stress.

We use mouse models of chronic stress as well as state-of-the-art neuroscience tools to investigate the role of specific brain pathways in the regulation of:

cardiovascular function.
anxiety-like behaviours.
food intake and body weight.

Research Groups

Neuroscience

Supervision Style

In three words or phrases: I am outcome-oriented, supportive, and organised. I try to be aware of individual students’ needs and preferences and will strive to help you reach your goals.

Provision of Training

I prefer to take responsibility for your technical training at first, leading to more independence later. We are a small lab, so I will do most of the training myself, but I expect everyone to support each other with learning the techniques they become particularly proficient in. Science relies on people paying it forward, so I also expect you to train others in the lab as your become more senior.

Progression Monitoring and Management

I firmly believe that progression monitoring and management isn’t just up to the preference of the supervisor, but should be decided based on the needs and wishes of the student. In addition, I fully expect this to change as you grow in independence and skill and as we come to understand each other better.

With time and as your confidence develops, I strive towards a hands-off, but supportive approach, where you take ownership of your own work and progression, but I am always available for help and to share in the disappointment of failed experiments or the excitement of new data.

Communication

As the lab is new, we will discuss amongst us the best way to communicate on a day-to-day basis. I expect this may include some communication outside normal hours, but I would encourage all my staff to maintain a healthy work-life balance. As an example, I rarely email on weekends or nights and unless urgent, I do not expect you to either. I am always happy to discuss any issues that are impacting your ability to fulfil your potential.

We keep an electronic lab book and keep all of our data on a shared drive. This ensures seamless sharing of protocols and data between lab members.

PhD Students can expect scheduled meetings with me:

In a group meeting

At least once per fortnight

In year 1 of PhD study

At least once per fortnight

In year 2 of PhD study

At least once per fortnight

In year 3 of PhD study

At least once per month

These meetings will be face to face, and I am usually contactable for an instant response on every working day.

Working Patterns

The timing of work in my lab is completely flexible, and (other than attending pre-arranged meetings), I expect students to manage their own time.

Notice Period for Feedback

I need at least 1 week’s notice to provide feedback on written work of up to 5000 words.

MIBTP Project Details

Current Projects (2025-26)

Primary supervisor for:

Brainstem circuits in stress-induced changes to behaviour and physiology

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Brainstem circuits in stress-induced changes to behaviour and physiology

Secondary Supervisor(s): Dr Emily Lane-Hill and Professor Mark Wall

University of Registration: University of Warwick

BBSRC Research Themes: Understanding the Rules of Life (Neuroscience and Behaviour)

Project Outline

A key function of the brain is to constantly monitor our environment – both our surroundings as well as our internal state. As an example, as we eat our stomach distends. The stretch in the stomach wall is sensed by the vagus nerve, which transmits the signal to the brain – primarily to the nucleus of the solitary tract (NTS). Here, neurons use that information to drive changes in behaviour and to limit further food intake, a process known as satiation.

However, food intake isn’t just controlled by our need for calories or the amount of food we have eaten. Our emotional state is a strong modulator of appetite. In response to brief stress, food intake robustly decreases. This process is driven by the brain: Data from our lab and others suggest that the same NTS neurons, which normally drive satiation, are hijacked by stress to suppress appetite and increase stress hormone release. However, while the NTS and the vagus nerve are reasonably well-studied in the context of appetite, we have very little understanding of how signals of stress are relayed from higher brain regions to the NTS.

PhD projects in our lab will focus on understanding how the brain controls behaviour and physiology in response to stress. We have three aims:

1) Anatomically map the brain circuits which relay signals of stress to the NTS

2) Characterise the impact of stress on neuronal signalling in the NTS

3) Determine the contribution of NTS neurons to stress-induced changes in behaviour and physiology.

To address these aims, we use transgenic mice expressing Cre recombinase under the control of the Crh promoter (Crh-Cre mice) to selectively and efficiently target these cells in vivo. Mice will be stereotaxically injected with viruses to label or manipulate NTS neurons and upstream circuits. Using immunolabelling and fluorescence microscopy, we will map the neuroanatomical profile of NTS neurons and the upstream circuits which drive their activity in response to stress¹. Whole cell patch-clamp electrophysiology and ex vivo calcium imaging will be conducted under the supervision of Dr Emily Lane-Hill and Professor Mark Wall. This will allow us to monitor the cellular responses to stimulation of the vagus nerve and application of stress-related signalling molecules (e.g. corticotropin-releasing hormone)². Using in vivo photometry recordings in awake behaving mice, we will investigate the activity of the NTS in response to stress. Finally, using pharmacology and chemo- and/or optogenetics, we will determine the role of NTS neurons and upstream circuits in stress-induced changes to food intake, stress hormone release and cardiovascular control³.

References

1. Holt, M. K. et al. Synaptic inputs to the mouse dorsal vagal complex and its resident preproglucagon neurons. J. Neurosci. Off. J. Soc. Neurosci. 39, 9767–9781 (2019).

2. Hisadome, K., Reimann, F., Gribble, F. M. & Trapp, S. Leptin directly depolarizes preproglucagon neurons in the nucleus tractus solitarius: electrical properties of glucagon-like Peptide 1 neurons. Diabetes 59, 1890–1898 (2010).

3. Brierley, D. I. et al. Central and peripheral GLP-1 systems independently suppress eating. Nat. Metab. 3, 258–273 (2021).

Previous Projects (2024-25)

Primary supervisor for:

Dissecting a novel brainstem-cerebellum circuit in food intake behaviour