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Professor Jack Mellor

Professor Jack Mellor

Professor Jack Mellor
BA, PhD(Cantab)

Professor in Neuroscience

Area of research

Synaptic plasticity and its role in learning and memory

Office G27
Biomedical Sciences Building,
University Walk, Bristol BS8 1TD
(See a map)

+44 (0) 117 331 1944

Summary

Our ability to learn and remember information about our environment is underpinned by synaptic plasticity. This process is fundamental to shaping who we are as individuals and is also implicated in many neurological and psychiatric disorders. Memory is fundamentally dependent on the behavioural context of learnt information and we aim to investigate the contextual factors that are important for the encoding of memory by synaptic plasticity at a neuronal circuit level.

We study this by considering the factors that regulate the induction of synaptic plasticity and the mechanisms underlying its expression. Currently this involves projects in the following areas:

1)      The role of acetylcholine and other neuromodulators in synaptic circuit function.

2)      The patterns of activity that induce synaptic plasticity.

3)      The mechanisms underlying postsynaptic neurotransmitter receptor trafficking.

We use a combination of techniques including in vitro and in vivo electrophysiology, 2-photon imaging, optogenetics, behavioural assays and computational modelling.

Biography

The group on retreat 2016

 

Retreat 2013

Lab retreat

Activities / Findings

The role of acetylcholine and other neuromodulators in synaptic circuit function.

Acetylcholine has a major neuromodulatory input to the hippocampus and has been shown by us and others to increase neuronal excitability and facilitate the induction of synaptic plasticity (Isaac et al., 2009; Buchanan et al., 2010; Petrovic et al., 2012; Teles-Grilo Ruivo and Mellor, 2013; Dennis et al., 2016). We have also shown that acetylcholine is released in the hippocampus and neocortex as an arousal signal but also in response to reward (Teles-Grilo Ruivo et al., 2017). We aim to define how the multiple effects of acetylcholine regulate neuronal circuits and therefore information processing including its effects on neuronal circuit oscillations (Atherton et al., 2016; Betterton et al., 2017). Through collaborations with Lilly and GSK we aim to use this information to develop compounds to enhance memory encoding and consolidation in the hippocampus.

The patterns of neuronal activity that induce synaptic plasticity.

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. 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. We make use of hippocampal place cell recordings that occur during spatial learning tasks. We then replay these activity patterns into neurones within a brain slice to assess their ability to induce synaptic plasticity (Isaac et al., 2009; Mistry et al., 2010; Sadowski et al., 2016). Using artificial neuronal activity patterns we can also determine the critical activity patterns required to induce synaptic plasticity (Buchanan and Mellor, 2007; Buchanan and Mellor, 2010; Chamberlain et al., 2013; Tigaret et al., 2016). Using a combination of 2photon imaging of spine calcium transients and computational modelling we have demonstrated the fundamental role for spine calcium regulation in the induction of synaptic plasticity (Rackham et al., 2010; Griffith et al., 2016; Tigaret et al., 2013, 2016)(MATLAB codes for computational modelling and calcium signal denoising available via links below).

The mechanisms underlying postsynaptic neurotransmitter receptor trafficking.

In collaboration with Dr Jonathan Hanley we investigate the role of PICK-1 in AMPA receptor trafficking (Dixon et al., 2009; Nakamura et al., 2011; Dennis et al., 2011; Rocca et al., 2013) and with Prof Jeremy Henley we investigate the role of SUMOylation in kainate receptor trafficking (Martin et al, 2007; Konopacki et al., 2011; Chamberlain et al., 2012). We use genetic modifications of specific neurones within hippocampal slices to assess the role of these proteins in synaptic glutamate receptor expression.

Teaching

BSc Neuroscience:

  • Synaptic Plasticity
  • Techniques in Neuroscience
  • Neurophysiology
  • Introduction to Neuroscience
  • Functional Neuroanatomy

Keywords

  • Electrophysiology

Skills

  • Epilepsy Alzheimer's Ischaemia

Processes and functions

  • Learning and memory

Methodologies

  • Brain slice electrophysiology whole cell patch clamp 2photon imaging in vivo electrophysiology Optogenetics

Memberships

Organisations

School of Physiology and Pharmacology

Other sites

Selected publications

Read more >

Recent publications

View complete publications list in the University of Bristol publications system

Networks & contacts

  • Mike Ashby - Bristol Claudia Clopath - Imperial College Jonathan Hanley - Bristol Jeremy Henley - Bristol Matt Jones - Bristol John Lowry - Maynooth Krasimira Tsaneva-Atanasova - Exeter

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