Swiss Federal Institute of Technology (ETH)
1999: Diploma in Biochemistry (subsidiary subjects: Biopsychology and Philosophy), Ruhr-University Bochum, Germany
Caledonian Research Foundation Fellow, Centre for Cognitive and Neural
Research fellow, Division of Neuroscience,
Research associate/ Scientist, Behavioural Neurobiology, Swiss Federal
Institute of Technology (ETH)
1998-1999: Studentische Hilfskraft (undergraduate assistant), Biopsychology Group, Ruhr-University Bochum, Germany
My interests are in the area of integrative and behavioural neuroscience: How do neuronal mechanisms generate adaptive behaviour? How does dysfunction of these mechanisms contribute to neurological and neuropsychiatric diseases?
From rapid memory encoding to adaptive behaviour – functional differentiation and integration in the hippocampus
Focusing on the hippocampus, my research is concerned with the brain mechanisms mediating memory and other behavioural functions, such as emotional, motivational, and sensorimotor functions, and, especially, the integration of these diverse functions. Combining behavioural testing with the manipulation and analysis of brain function in rats, I study hippocampal functions, the underlying mechanisms and connectivity, and the consequences of hippocampal dysfunction that characterises many neuropsychiatric populations.
Functional-anatomical model of the hippocampus: implications for behaviour in health and disease
My research is led by the idea (see Bast T, 2007, Rev Neurosci; Bast, 2011, Curr Opin Neurobiol) that the hippocampus integrates (i) anatomical and physiological substrates of certain types of rapid information encoding (including functional connectivity to entorhinal cortex) with (ii) direct links (via prefrontal cortex and subcortical sites) to behavioural control functions, such as emotional, motivational, executive, and sensorimotor processes (see figure). Thereby, in humans and other mammals, normal hippocampal function may enable rapid place and episodic(-like) learning (i.e., encoding of events and their spatio-temporal context), and the translation of such learning into behaviour. Examples of such behaviour include our returning to where we parked our car or placed our key this morning, or a rat’s returning to where it found food or safe refuge on a previous occasion. On the other hand, permanent hippocampal damage may result in striking and specific memory deficits, as reported in the famous case studies of H.M. and other patients; furthermore, hippocampal dysfunction, as found in schizophrenia, mood, and anxiety disorders, may, apart from memory deficits, also contribute to other functional impairments, including aberrant emotional, motivational, sensorimotor and executive functions.
To study brain, especially hippocampal, substrates of complex behaviour, I have been combining sophisticated behavioural testing with brain manipulation and analysis in rats. Main approaches include:
· Well-established and innovative behavioural tests to examine (i) learning and memory (including animal models relevant to declarative and episodic memory) and (ii) emotional and sensorimotor processes (animal models relevant to schizophrenia and anxiety disorders). Specific paradigms include: event-arena procedures (food-reinforced place-memory tests in a novel dry-land apparatus), watermaze procedures, fear conditioning, prepulse-inhibition and startle testing, open-field testing.
· Selective neuropharmacological (intracerebral microinfusions) and brain-lesion (cytotoxic lesions, fibre cuts) techniques to manipulate (i) specific components of the hippocampal circuitry and their interaction and (ii) cortical and subcortical structures connected to the hippocampus.
· In vivo electrophysiology, in vivo microdialysis, anatomical techniques, and, most recently, in vivo MRI to characterise the pathways and mechanisms underlying the behavioural significance of the different components of the hippocampal circuitry.
Functional significance of hippocampal and prefrontal disinhibition in schizophrenia: integrative in vivo studies in rat models
Disinhibition, i.e. impaired inhibitory GABA transmission, in the prefrontal cortex and hippocampus has emerged as key feature of schizophrenia pathophysiology (see here). In current work, led with Marie Pezze, we examine if and how prefrontal and hippocampal disinhibition disrupt cognition and behaviour. To this end, we study the neural-network effects and behavioural/cognitive deficits resulting from such disinhibition in rodent models. The work on hippocampal disinhibition is guided by hypotheses based on the functional-anatomical model of the hippocampus described above (see Bast, 2011, Curr Opin Neurobiol).
Further information: Bast T, McGarrity S, Mason R, Fone KC, Pezze M (2013) S. 28.03 Schizophrenia-related behavioural deficits caused by hippocampal and prefrontal disinhibition. Eur Neuropsychopharmacol 23: S153; McGarrity S, Mason R, Fone KC, Pezze M, Bast T (2013) P1.j.026 Cognitive deficits caused by hippocampal disinhibition: attentional and memory deficits. Eur. Neuropsychopharmacology 23, S296-297;
Pezze M, McGarrity S, Mason R, Fone K, Bast T (2014) Too little and too much: hypoactivation and disinhibition of medial prefrontal cortex cause attentional deficits. J Neurosci 34: 7931-7946
Hippocampal learning-behaviour translation: prefrontal and subcortical substrates
It is firmly established that the hippocampus is required for certain types of everyday learning, including place learning, and we have achieved remarkable insights into the underlying neural mechanisms of information encoding and storage. However, how is, for example, place memory translated into appropriate behaviour, such as returning to that place? A key idea is that this translation may require interactions of the hippocampus with brain sites playing central roles in behavioural control, such as prefrontal cortex and subcortical sites, including striatum (Bast, 2011, Curr Opin Neurobiol). Consistent with this idea, we provided evidence that the direct translation of rapid place learning into behavioural performance depends on a region of the hippocampus where neural substrates of accurate place encoding converge with links to prefrontal and subcortical sites (Bast et al, 2009, PLoS Biol). In current work, we aim to determine which prefrontal and subcortical sites contribute to the learning-behaviour translation and how the hippocampus interacts with these sites.
Stephanie McGarrity, 1+3 MSc/PhD student, start:
September 2010, funding: