Our ability to learn and remember information about our environment is thought to be underpinned by the process of synaptic plasticity. This means that during learning episodes, synapses are stimulated by specific patterns of activity that lead to the induction of synaptic plasticity. Subsequently, plasticity is expressed either by the insertion or removal of postsynaptic neurotransmitter receptors or by changes in the amount of neurotransmitter released from the presynaptic terminal.

Research in our laboratory is focused on what regulates the induction of synaptic plasticity and also the mechanisms underlying its expression. Currently we are studying, 1) The patterns of activity that induce synaptic plasticity, 2) The regulation of neuronal excitability and the effect this has on the induction of synaptic plasticity, and 3) The mechanisms underlying postsynaptic glutamate receptor trafficking. This work is mainly performed using electrophysiological recordings from neurones in brain slices.

Current projects:

The neuronal activity patterns required for synaptic plasticity induction.
The hippocampus is believed to encode episodic memories (or memory for events) by the process of synaptic plasticity. However, the precise events that occur during learning to induce synaptic plasticity are currently unknown. Finding out what these are would represent a major advance in our understanding of how learning and memory are encoded. We investigate this problem by analysing the patterns of neuronal activity that induce synaptic plasticity and how these patterns relate to those that occur during learning episodes. In collaboration with Prof Robert Muller and Dr Matt Jones, we make use of hippocampal place cell recordings that occur in the hippocampus during spatial learning tasks. We can then replay these activity patterns into neurones within a brain slice to assess their ability to induce synaptic plasticity (Isaac et al., 2009). Using artificial neuronal activity patterns we can also determine the critical activity patterns required to induce synaptic plasticity (Buchanan and Mellor, 2007).

Regulation of neuronal excitability and its effect on synaptic plasticity.
Changes in neuronal excitability brought about by neuromodulators or long-term changes in ion channel properties alter the manner in which neurones process incoming information. We are interested in understanding how this occurs and how it affects the induction of synaptic plasticity. Previously, we found a role for ion channel modulation in hippocampal granule cell excitability (Mistry and Mellor, 2007) and we are currently investigating how this affects synaptic plasticity. Recently, we have also found a critical role for the neuromodulator acetylcholine in the induction of synaptic plasticity by naturally occurring activity patterns (Isaac et al., 2009) and we are currently investigating the mechanisms underlying the action of acetylcholine.

Glutamate receptor trafficking.

In collaboration with Dr Jonathan Hanley we investigate the role of PICK-1 in AMPA receptor trafficking (Dixon et al., 2009) and with Prof Jeremy Henley we investigate the role of SUMOylation in kainate receptor trafficking (Martin et al, 2007). We use genetic modifications of specific neurones within hippocampal slices to assess the role of these proteins in synaptic glutamate receptor expression.

Isaac, J.T., Bucahanan, K.A., Muller, R.U. and Mellor, J.R. (2009). Hippocampal place cell firing patterns can induce long-term synaptic plasticity in vitro. Journal of Neuroscience 29, 6840-6850.

Slice electrophysiology