Motivational memory: role of nicotinic receptors in synaptic plasticity in the prefrontal cortex and its limbic connections.
A challenge in neuroscience research is to understand the numerous learning and memory processes that are key to life. One such process is motivational learning. Motivation or ‘drive’ is a critical determinant of success in life and is governed, in part, by the prefrontal cortex (PFC). However, this process can also be hijacked by adverse external reinforcers such as drugs of abuse, gambling etc. Motivational learning can be modelled in laboratory animals using the Conditioned Place Preference technique. This exploits a form of Pavlovian conditioning whereby an animal learns to associate a particular environment with a rewarding or aversive stimulus.
Mammalian learning and memory processes are complex systems involving interplay between different neuronal populations, neurotransmitters, receptors and downstream signalling cascades. The mesocorticolimbic pathway (consisting of dopaminergic neurones projecting to the nucleus accumbens and PFC) is heavily implicated in motivational behaviour. This pathway interacts with glutamatergic inputs at multiple levels. Plasticity at glutamate synapses provides a paradigm for molecular and cellular changes underlying memory formation. Modulation of this plasticity by other transmitter systems (acetylcholine, dopamine) is less well defined and forms the basis of this proposal.
Nicotinic acetylcholine receptors (nAChRs) modulate the crosstalk between glutamate and dopamine pathways in the PFC (Livingstone & Wonnacott, 2009). Moreover, nAChRs have been implicated in learning and memory mechanisms in many brain regions including the PFC (dos Santos Coura & Granon, 2012).
This project will take a trans-disciplinary approach, integrating in vivo behavioural learning paradigms, brain-slice electrophysiology and ex vivo neurochemical techniques to elucidate the specific roles, and mechanisms, of nAChRs in mediating or modulating motivational learning processes. The project will build upon recent findings from our group that show inhibition of the α7 subtype of nAChR to play a distinct role in motivational learning in vivo. In separate experiments using brain-slice electrophysiology, we have discovered that the α7 nAChR plays a key modulatory role in synaptic plasticity processes in the prefrontal cortex. The proposed project aims to integrate these approaches.
The student will join a vibrant group of young researchers studying other aspects of this topic. During the project, the student will learn to perform a broad range of methods, including the conditioned place preference paradigm, brain-slice electrophysiology, ex vivo protein-cross-linking, western blot and receptor autoradiography techniques. The student will exploit this powerful multidisciplinary combination of techniques to address the question of how α7 nAChRs affect synaptic plasticity and learning and memory processes that underpin motivational learning.
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Dos Santos Coura & Granon (2012) Psychopharmacology 221:1-18
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