Please Note: The main page lists projects via BBSRC Research Theme(s) quoted and then relevant Topic(s).
Mapping Plasticity Across Species: Increasing our understanding of translational research
Secondary Supervisor(s): Dr Helen Eachus
University of Registration: Aston University
BBSRC Research Themes: Understanding the Rules of Life (Neuroscience and Behaviour)
Project Outline
My lab, and my collaborators, are generally interested in how the brain develops and how synaptic plasticity drives the normal creation of complex circuits. We also want to know how this process, and the neural oscillations and activity that arise from it, can go wrong sometimes and give rise to a number of neurological and psychiatric conditions. To better understand all of these inter-dependent phenomena, we need to focus on the physiology of neurons, synapses and networks throughout the lifecourse. Doing research of this nature requires investigations of cell and network activity at a number of levels – in my lab we primarily use electrophysiology from a cell/synapse level (e.g. patch clamp) all the way up to behaviour-linked EEG recordings of rodents, alongside imaging and molecular biology. But the molecular and functional manipulations we can make with each model organism, or the in vitro analogues we use (such as organotypically-cultured brain tissue from humans or rodents) need to be combined in such a way that is useful to our understanding of neuronal physiology.
To that end, it’s important to map and compare the functions of cells and circuits across organisms and to make sure that what we do in, for example, a zebrafish can be successfully translated to a rodent and on to a human. There has been a lot of research as to the development and plasticity of the individual species, but more needs to be done to compare circuit development and cellular plasticity across species so we can perform more effective translational studies.
Aim
This project will use a combination of electrophysiology, imaging and molecular biology to perform manipulations of synaptic plasticity in zebrafish and rats, mapping the plasticity phenotypes across suitable brain areas and developmental time periods. We will:
- Perform patch-clamp studies with spike timing-dependent plasticity protocols in ex vivo brain preparations from rats and zebrafish, followed by histological reconstruction and imaging to show dendritic structure and identify cell types.
- Develop an in vivo model of acute zebrafish plasticity that can recapitulate important aspects of what would be expected in a similarly-developed rat.
- Investigate how receptor expression and dendritic spine properties are altered by cumulative experience-dependent plasticity and what cross-species similarities (and differences) exist.
Methods Involved
We will use a range of electrophysiological, molecular biology, histology and imaging techniques, alongside computational analysis and behavioural observations. Experimental approaches include:
Patch-clamp electrophysiology: using both in vivo and in vitro recordings of single cells within functional networks, we can gain understanding of synaptic and cellular activity and use this to carefully manipulate synaptic plasticity in a highly physiological manner.
Field and EEG recordings: allow us to look at ensemble activity from large groups of neurons up to the whole brain, and compare our cellular results to ensemble and oscillatory activity.
Laser and fluorescent imaging: allow us to reconstruct individual neurons, trace long-range neural projections and map protein expression across brain areas.
Significance: This project will greatly enhance our ability to draw conclusions across commonly-used model species, help us gain a better understanding of neurodevelopment and pave the way for future projects investigating disease states in a focussed, translational manner.
References
Greenhill, Ranson and Fox (2015) - Hebbian and Homeostatic Plasticity Mechanisms in Regular Spiking and Intrinsic Bursting Cells of Cortical Layer 5. Neuron, 88(3), 539-52.
Suppermpool et al (2024) - Sleep pressure modulates single-neuron synapse number in zebrafish. Nature 629, 639-645.