SSA: Changes in brain circuitry caused by early life adversity
Lead Research Organisation:
University of Bristol
Department Name: Physiology and Pharmacology
Abstract
The early life experiences of newborn babies and infants are a key determinant in their future mental health. Early life adversity within the mother-infant relationship is highly significant in determining a child's future susceptibility to a range of psychiatric disorders including anxiety and depression. Early life adversity causes stress in infants which raises cortisol levels and activity in the hypothalamic-pituitary-adrenal (HPA) axis. However, we know very little about the changes in brain circuit development caused by early life adversity and stress.
The circuits controlling positive and negative affect (or emotions) and those that regulate the stress response to emotional situations are thought to reside principally in the amygdala and hippocampus. In particular, positive and negative affective behaviour is thought to be encoded by the strength of synaptic inputs to genetically and anatomically defined subsets of neurons in the hippocampus and amygdala. Thus we propose that adverse early life events will lead to altered synaptic strengths in these hippocampal and amygdala circuits compared to normal early life experiences. Furthermore, reversing these changes in synaptic strength could ameliorate the behavioural effects of early life adversity in adults.
This project will test this hypothesis using rodent models of maternal separation and behavioural tests of positive versus negative affective behaviour developed by the Robinson group. The primary objective will be to determine how these early life effects on developing circuits impact on adult behaviour, particularly affective behaviour and decision-making. By making electrophysiological measurements of synaptic transmission coupled with genetic and anatomical identification of neuronal subtypes we will investigate how these circuits are altered by the model of early life adversity. The aim is to subsequently reverse these circuit changes using optogenetics or pharmacology guided by a mathematical model of the circuit dynamics. The ultimate goal will be to find out if manipulating synapses within the circuits underlying behaviour using pharmacological or optogenetic tools is capable of changing the balance of positive and negative affect in adult animals.
The student will be trained in animal behavioural paradigms, in vitro and in vivo electrophysiology and genetic manipulation of neuronal subtypes. In addition, through collaboration with Krasimira Tsaneva-Atanasova the project also aims to use computational models to predict the likely outcome of synaptic modifications on behaviour.
The circuits controlling positive and negative affect (or emotions) and those that regulate the stress response to emotional situations are thought to reside principally in the amygdala and hippocampus. In particular, positive and negative affective behaviour is thought to be encoded by the strength of synaptic inputs to genetically and anatomically defined subsets of neurons in the hippocampus and amygdala. Thus we propose that adverse early life events will lead to altered synaptic strengths in these hippocampal and amygdala circuits compared to normal early life experiences. Furthermore, reversing these changes in synaptic strength could ameliorate the behavioural effects of early life adversity in adults.
This project will test this hypothesis using rodent models of maternal separation and behavioural tests of positive versus negative affective behaviour developed by the Robinson group. The primary objective will be to determine how these early life effects on developing circuits impact on adult behaviour, particularly affective behaviour and decision-making. By making electrophysiological measurements of synaptic transmission coupled with genetic and anatomical identification of neuronal subtypes we will investigate how these circuits are altered by the model of early life adversity. The aim is to subsequently reverse these circuit changes using optogenetics or pharmacology guided by a mathematical model of the circuit dynamics. The ultimate goal will be to find out if manipulating synapses within the circuits underlying behaviour using pharmacological or optogenetic tools is capable of changing the balance of positive and negative affect in adult animals.
The student will be trained in animal behavioural paradigms, in vitro and in vivo electrophysiology and genetic manipulation of neuronal subtypes. In addition, through collaboration with Krasimira Tsaneva-Atanasova the project also aims to use computational models to predict the likely outcome of synaptic modifications on behaviour.
Organisations
People |
ORCID iD |
Jack Mellor (Primary Supervisor) | |
Matthew Wilkinson (Student) |
Studentship Projects
Project Reference | Relationship | Related To | Start | End | Student Name |
---|---|---|---|---|---|
BB/M009122/1 | 01/10/2015 | 31/03/2024 | |||
1793253 | Studentship | BB/M009122/1 | 01/10/2016 | 31/03/2021 | Matthew Wilkinson |
Description | GW4 Early career neuroscience day travel bursary |
Amount | £500 (GBP) |
Organisation | GW4 |
Sector | Academic/University |
Country | United Kingdom |
Start | 10/2019 |
End | 11/2019 |
Description | Guarantors of Brain - Brain Travel Award |
Amount | £1,000 (GBP) |
Organisation | Guarantors of Brain |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 10/2019 |
End | 11/2019 |
Description | University of Bristol Alumni Foundation Travel Grants |
Amount | £450 (GBP) |
Organisation | University of Bristol |
Sector | Academic/University |
Country | United Kingdom |
Start | 04/2019 |
End | 05/2019 |
Description | Bristol Neuroscience Festival |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Schools |
Results and Impact | 3 day neuroscience festival hosted by the university of Bristol. Hundred of school children engaged with over 30 activities relating to neuroscience as well as the general public. |
Year(s) Of Engagement Activity | 2018 |
URL | http://www.bristol.ac.uk/neuroscience/bnf/ |
Description | Cheltenham Science Festival |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Schools |
Results and Impact | Involvement in the Cheltenham science festival talking about science to the general public |
Year(s) Of Engagement Activity | 2018 |
URL | https://www.cheltenhamfestivals.com/science |
Description | School visit (Brunel Academy) |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Schools |
Results and Impact | Visit to school with workshop of activities and short talks about neuroscience. |
Year(s) Of Engagement Activity | 2018 |