My research examines how a brain circuit consisting of the hippocampus, prefrontal cortex and connected subcortical sites mediates and integrates important cognitive functions, including everyday-type memory (e.g., memory for places and events) and attention, and other behavioural processes (emotional, motivational, sensorimotor).
In addition, I study how dysfunction in this neural circuit causes cognitive and behavioural deficits. My major approach to address these questions is to combine sophisticated behavioural testing with a wide range of in vivo neurobiological methods to analyse and manipulate brain function in rat models. A concise overview of main lines of research and key underlying ideas can be found in our recent reviews ( Bast, 2011, Curr Opin Neurobiol; Bast et al., 2017, Br J Pharmacol).
Current lines of research
Hippocampo-prefrontal/subcortical interactions mediating the hippocampal learning-behaviour translation:Continuing work on the hippocampal learning-behaviour translation ( Bast et al, 2009, PLoS Biol; also see press release), we aim to identify prefrontal and subcortical mechanisms underlying behavioural performance based on hippocampus-dependent rapid-place learning and to characterize how the hippocampus interacts with these sites. We have begun to collaborate with Stephen Coombes and colleagues (Mathematics, University of Nottingham) to synthesize relevant neurobiological findings into neuro-computational models.
Off balance - cognitive deficits caused by hippocampo-prefrontal neural disinhibition: Neural disinhibition, i.e. GABA dysfunction, in hippocampus and prefrontal cortex has been implicated in many brain disorders characterised by cognitive deficits, including schizophrenia, cognitive ageing and Alzheimer's disease. We aim to determine if and howprefrontal and hippocampal disinhibition disrupt cognition and behaviour and to explore new pharmacological treatment strategies. To this end, we study the neural-network effects and behavioural/cognitive deficits resulting from such disinhibition in rodent models ( Pezze et al, 2014, J Neurosci; McGarrity et al, 2017, Cereb Cortex; Bast et al., 2017, Br J Pharmacol; also see press releases: 2014, 2016, 2017)
Hippocampo-prefrontal-subcortical circuit and aversive stimulus processing - fear memory and pain: Previous research, including our own, revealed a key role for the hippocampo-prefrontal-subcortical circuit in fear memory (e.g., Bast et al, 2003, Hippocampus; Pezze et al, 2003, Cereb Cortex; Heath et al, 2015, Psychopharmacology; Wang et al, 2015, Hippocampus). I continue collaborative research into the role of this circuit in fear behaviour in collaboration with Carl Stevenson (Biosciences, University of Nottingham). Recently, I have also become interested in how this circuit is implicated in chronic pain conditions. We have translational studies on the way to examine how chronic pain affects components within the hippocampo-prefrontal-subcortical circuit, as well as the cognitive and behavioural functions mediated by these components (in collaboration with colleagues at the Arthritis Research UK Pain Centre and in Life Sciences, University of Nottingham).
New applications of translational brain imaging methods in rodents: Methods developed for the non-invasive imaging of the human brain (MRI and other metabolic imaging methods) could substantially complement the neurobiological approaches traditionally used to characterise brain structure and function in rodent models. I am involved in projects adapting such methods for new applications in rodent models.
Studies of human cognition, using translational behavioural tests similar to our rodent paradigms: We have adapted a key rodent test of hippocampus-dependent rapid place learning, the delayed-matching-to-place watermaze test (e.g., Bast et al, 2009, PLoS Biol; da Silva et al., 2014, Learn Memory), for human testing, using a virtual maze on a computer. Studies using this new virtual maze task, and other translational behavioural tests, in human participants will facilitate translation of findings from rodent model studies to humans.
PDF files of selected publications can be found at: http://www.psychology.nottingham.ac.uk/staff/lpztb1/