Hippocampo-prefrontal-subcortical circuit in cognition and behaviour

The brain circuit consisting of the hippocampus, prefrontal cortex and connected subcortical sites mediates and integrates important cognitive and behavioural functions, including memory, attention, cognitive control, emotional, motivational and sensorimotor processes. This circuit may play a key role in enabling the translation of every-day memories (e.g., of where you parked your car), which depend on the hippocampus, into adaptive behaviour (e.g., getting back to the car), for which prefrontal-subcortical circuits are vital (Bast, 2011, Curr Opin Neurobiol). Moreover, dysfunction within this hippocampo-prefrontal-subcortical circuit, especially within the hub regions - hippocampus and prefrontal cortex - may disrupt the wide range of cognitive functions integrated within this circuit. Consistent with this, dysfunction within this circuit has been implicated in key cognitive and behavioural impairments characterizing neuropsychiatric disorders (Bast, 2011, Curr Opin Neurobiol; Bast et al., 2017, Brit J Pharmacol).
Research questions
In this project, we will further examine the role of the hippocampo-prefrontal-subcortical circuit in adaptive and dysfunctional behaviour and cognition. The specific research questions can be determined depending on the student's interest. Two main topics of our research include:
Hippocampal learning-behaviour translation: Which prefrontal and subcortical regions contribute to behaviour based on hippocampus-dependent place learning, and by which mechanisms?
Importance of GABAergic neuronal inhibition of balanced neural activity: Imbalanced neural activity within the hippocampal-prefrontal-subcortical circuit, caused by changes in inhibitory GABA transmission, has come to the fore in important brain disorders, including age-related cognitive decline, Alzheimer's disease and schizophrenia (Bast et al., 2017, Br J Pharmacol). How do such imbalances affect distinct cognitive and behavioural functions? Can they explain symptoms characterizing these disorders?
Methods
To address these questions, we will combine a wide range of neuroscience methods in rats. We will combine neuropharmacological modulation of specific brain regions by intracerebral drug microinfusions with translational tests of specific cognitive and behavioural functions (including learning and memory, attention, behavioural flexibility, fear, sensorimotor processes). In vivo electrophysiological methods will be used to characterise changes in neural activity patterns and interactions between relevant brain sites. A good overview of key methods can be found in our recent papers (Pezze et al., 2014, J Neurosci; McGarrity et al., 2017, Cereb Cortex; Gwilt et al., 2020, Hippocampus; Williams et al., 2022, eNeuro). Additionally, depending on interest and specific project objectives, students will have the opportunity to work with computational neuroscientists to synthesise experimental findings into neuro-computational models (e.g., Tessereau et al., 2021, Brain Neurosci Adv) or to use advanced analytical methods to analyse our experimental data (e.g., Maggi et al., 2022, bioRxiv); to apply 'translational' brain imaging methods to characterise neuronal network changes in a way that enables direct comparison to human brain imaging studies; to apply modern neural tract tracing methods (involving 'clarity' and light-sheet microscopy) and pharmacogenetic methods for neuron-type specific manipulations (which we are currently setting up)