MathsNet: Research Student Directory

Name Jurkus, Regimantas
Group Mathematical Medicine and Biology
Room  ,  
Telephone +44 (0) 115   [direct dial]
Email
Thesis Title Cannabidiol modulation of fear memory processing: a combined experimental and theoretical modelling study
Thesis Abstract Learning from experience and adapting to a changing environment are essential for survival. Understanding how the brain uses different memories to guide appropriate behaviour under varying circumstances is thus an important challenge in biology. Communication between reciprocally connected brain areas forming functional neural circuits underpins memory function. However, the mechanisms underlying the representation of different related memories, and how these memories can compete to control behaviour, are poorly understood. These memories might be represented by multiple inter-connected areas communicating via distinct yet overlapping neural circuits. We will test this idea by examining the neural circuitry underpinning contextual fear and extinction memories. During contextual fear conditioning a novel environment is associated with an adverse consequence like shock presentation. Returning to the environment after conditioning initially elicits a behavioural fear response; learning that certain contexts predict threat is essential for survival. However, prolonged exposure to the environment without shock presentation reduces fear responding via extinction. Through this process a new association between the environment and shock is formed such that the environment now predicts that shock no longer occurs. Extinction competes with the original conditioning to inhibit fear; learning that contexts no longer predict threat allows for adaptation to environmental change, which also enhances survival. Various brain areas, including subregions of the prefrontal cortex and hippocampus, are involved in contextual fear and extinction memory processing. The prelimbic (PL) and infralimbic (IL) cortex mediate contextual fear and extinction memory, respectively. In contrast, the ventral hippocampus (VH) is involved in both memory processes. Importantly, the VH projects to both the PL and IL. However, the extent to which communication within these overlapping neural circuits plays a role in mediating contextual fear and extinction memories remains unclear. Moreover, the neurochemical mechanisms involved in modulating neural circuit function underlying contextual fear and extinction memory are poorly understood. Cannabidiol is the main non-psychotropic constituent of cannabis and has opposing effects on learned fear and extinction, impairing the former and enhancing the latter. Thus cannabidiol regulation of fear and extinction memory may provide a pharmacological tool to modulate neural circuit function underpinning contextual fear and extinction memory. Although the PL and IL are sites of action of cannabidiol, the role of the hippocampus in mediating its regulation of contextual fear and extinction is unknown. This project will combine experimental and computational neuroscience approaches to determine the role of the VH-PL and VH-IL circuits in mediating contextual fear and extinction memory. It will also determine the effects of cannabidiol on VH-PL and VH-IL circuit function underlying contextual fear and extinction memory processing. We will examine in vivo neural activity concurrently in VH, PL and IL during behavioural testing in rats to assess correlated activity between these brain areas in response to cannabidiol (or vehicle). We will also devise computational models of VH-PL and VH-IL circuit function, and their modulation by cannabidiol, which are inspired by the experimental data generated.
School contact information School of Mathematical Sciences
University of Nottingham
University Park
Nottingham, NG7 2RD
UK
Tel: +44 (0) 115 951 4949
Fax: +44 (0) 115 951 4951