Dr. Christopher N Connolly

Reader in Neurobiology

Understanding how neuronal dysfunction contributes to pesticide toxicity in bees and stroke/neurodegenerative disease in humans


Division of Neuroscience
Mail Box 6, Level 6
Ninewells Medical School

Phone Number:

+(44) 01382 383105

Email Address:



1999-Present:    Reader in Neurobiology, Division of Neuroscience, University of Dundee

1993-1999:        Postdoctoral Research Fellow, MRC LMCB, University College London

1989-1993:        PhD student, Imperial College/ University College London 

1979-1984:         Research Assistant, Wellcome Research Laboratories


PhD in Cell Biology (1993), MRC LMCB (Profs. DC Cutler & CR Hopkins), University College London

MSc in Molecular Genetics (1989), University of Leicester (Research Project: Profs. A. Jeffries & A. Cashmore)

BSc (Hons) in Genetics (1987), University of Leeds (Research Project: Prof. Cove)


Winner Stephen Fry Award for Public Engagement (2014).

Scottish Executive Life Sciences Award finalist (2015).

University roles:

Member of University of Dundee BBSRC Excellence with Impact Committee (2013-2016)

Member of the University of Dundee Public Engagement Committee (2014-Present)

Member of the School of Medicine Safety Committee (2010 – Present)

Member of the University of Dundee Radiation Committee (2009 – Present)

Mentor on the University of Dundee/St. Andrews mentoring scheme (2010- Present)

External roles:

Editor for Journal of Biological Chemistry (2013-2018)

Expert Assessor for Carnegie Trust (2015-18)


Introduction Movie

The main focus of this laboratory is the study of the role of ligand-gated ion channel biology to the control of excitation/inhibition in neurons of the brain. Our studies concentrate on two family members of the cys-loop superfamily of ligand-gated ion channels (GABAA and 5-HT3 receptors) as well as the NMDA receptor subtype of glutamate receptors, to obtain an understanding of how such mechanisms contribute to pathological states such as epilepsy and ischaemia.

Cys-loop receptor assembly and trafficking

This research investigates the mechanisms of the Cys-loop (in particular 5-HT3 and GABAA) receptor biogenesis and how transport to the cell surface is controlled. We are using recombinant expression of novel cDNA constructs expressing chimaeric ‘living colour’ fusion proteins. We are using a combination of cell line, primary neuronal culture, organotypic culture and transgenic models to study these events.

Movie1: RIC-3a aggregation

Movie 2: RIC-3a aggregates consume ‘RIC-3 diffuse slicks’

Movie 3: RIC-3d in Golgi

Our interests include the role(s) of chaperone molecules such as RIC-3 on 5-HT3 receptor trafficking and targeting with a particular focus on how these processes are influenced by excessive exposure to serotonin. Such events may be relevant to psychosis, depression and irritable bowel syndrome. Similarly, we are interested in the responses (dynamic trafficking) of GABA(A) and glutamate (NMDA) receptors following excessive exposure to GABA and glutamate. Understanding how such a balance in excitatbility is altered may provide important information regarding alterations in behaviour and future vulnerability to neurotoxic insults.

Spreading neurotoxicity: Spreading poison versus spreading warning

We have shown previously that rapid (<10 min) neuronal morphological changes occur in response to neuronal insults as a result of NMDA receptor activation. It is not clear whether these changes are an attempt at neuronal protection or are early signs of neuronal toxicity. Interestingly, neuronal inactivation is also induced by excessive glutamate receptor activation. We are currently studying the events that follow a localised insult to monitor how these responses spread throughout neuronal networks and what impact this has to neuronal survival. We are investigating how neuronal inactivation is achieved and whether this process may be manipulated to provide better neuroprotection within the surrounding (penumbra) region of a lesion and thus limiting the spread of neurotoxicity.

Movie 4: Neuronal dendritic beading (blue), mitochondrial collapse (red) and mitochondrial depolarisation (green) in response to excess glutamate.

Movie 5: Sequential neuronal beading (blue), mitochondrial collapse (red) and mitochondrial depolarisation (green) in response to oxygen-glucose deprivation.



Dendritic beading of a hippoocampal neuron following an excitotoxic insult

Nervous System of Bees

The effects of miticides and pesticides on the nervous system of bees



Professor Neil Millar (UCL), Dr Nigel Raine (Royal Holloway), Dr Geraldine Wright (Newcastle), and Dr Christopher Connolly (Dundee). Photograph taken by Nancy Mendoza (BBSRC) at the Insect Pollinators Initiatve launch in June 2010.


This is a multi-disciplinary research programme (~£2M) studying the effects of miticides and pesticides on the nervous system on bees (honeybees and bumblebees). This involves research at the cellular and pathway level (University of Dundee and UCL), individual bees and whole colonies (Newcastle University and Royal Holloway University of London) and involves field studies (Scottish Beekeeper’s Association). This multi-disciplinary approach will allow us to integrate laboratory-based findings at multiple distinct levels into cohesive conclusions on the effects of these chemicals to bee health and correlate this information to the experiences of beekeepers. This high profile issue (Guardian article) and (AVAAZ.org) ) is highly controversial. To investigate this issue, this programme (2011-2015) has been funded by the Insect Pollinators Initiative as part of the Living with Environmental Change (LWEC) partnership. Further information.


Honeybee decline has been identified as a major world problem and is estimated to contribute in excess of £440M to the UK economy every year. A similar decline in other native pollinators is also a major concern for our biodiversity and food security. The major identified natural threats to UK honeybees are Varroa mites and the viruses they transmit, Foul Brood diseases, Nosema and Small Hive Beetle. The control of Varroa infestation often involves the chronic exposure of a colony to miticides. These miticides target the Varroa nervous system, in particular, cholinergic neurotransmission. The central basis of our hypothesis is that chronic miticide treatment may put honeybees under significant chemical stress to the extent that they become vulnerable to otherwise sub-toxic doses of other pesticides. Honeybee pollination is important for the fertilization of a large amount of our fruit, nuts, vegetables and livestock feed. The other major pollinator of crops and native plants are bumblebees as they fly earlier in the season and are increasingly important for the pollination of UK crops such as potatoes, berries, red clover, alfalfa and greenhouse crops. The loss of bees would also have a major impact on the production of native food for wildlife, with unknown knock-on effects at the ecosystem level. While it is widely acknowledged that honeybee populations are in global decline, how the different factors are interacting to produce this decline is poorly understood. In addition to the natural threats and the chronic use of miticides, bees are also exposed to sub-toxic levels of pesticides (including herbicides and fungicides) that are vital to maintenance of crop quality and yield and so, food security. When bees are exposed to multiple pesticides, these may synergize to cause enhanced toxicity to bee populations. In order to understand the potential for such synergistic threats, we need to consider the major neuronal targets in bees for the agents used (miticides and insecticides). These targets include action potential firing (sodium channels) and the balance between excitatory (cholinergic signalling) and inhibitory (GABA and glutamate-gated chloride channels) neurotransmission (Figure 1). Perturbation of these pathways disrupts brain function in all animals, leading to locomotor, behavioural or social problems. The insect brain structure involved in bee learning (olfactory and visual) is the mushroom body. Cholinergic neurotransmission is the major excitatory pathway in this brain structure. The responses are terminated by the rapid inactivation of the released acetylcholine (ACh), by acetylcholinesterase (AChE). In insects, this excitatory activity is balanced by the inhibitory actions of chloride-gated GABA or glutamate receptors. The pharmacological manipulation of any these individual steps may have a profound effect on honeybee learning.



Given the central importance of ACh signalling in the insect brain, it has become a major target for the development of insecticides. The AChE inhibitors (e.g. coumaphos [Checkmite]), have been shown to alter neuronal morphology and bee foraging behaviour. Interestingly, AChE activity decreases naturally in adult foragers and this decrease correlates with enhanced olfactory learning. Pyrethroids, (e.g. fluvinate in Apistan) target neurotransmission by potentiating the voltage-gated sodium channels (Nav’s) and so prolongs action potential firing. Neonicotinoid pesticides act as partial agonists at honeybee nAChRs, but are not inactivated by AChE and may lead to prolonged receptor activation. Some neonicotinoids are more resistant to cytochrome P450 detoxicification, or generate toxic metabolites. That neonicotinoids decrease bee foraging behaviour [9] is counter-intuitive, suggesting that the role of these pesticides is inconsistent. However, the long-term consequences of the chronic exposure to neonicotinoids, such as receptor desensitization and agonist-induced receptor internalization, are unknown. To add to the confusion, imidacloprid (a neonicotinoid) exhibits “off target” activity by operating as a GABA receptor antagonist. Other pesticides, including cyclodienes and phenylpyrazoles, also inhibit GABA receptors, whereas, the ‘natural’ pesticide, thymol (the active ingredient of the miticide, Apiguard) is a GABA receptor agonist. Avermectins target the other major inhibitory receptor, the glutamate-gated chloride channel. Domestic insecticides also contain ‘synergist’ agents, e.g. piperonyl butoxide, to reduce the pyrethroid detoxification by cyctochrome P450. Despite this potential for pesticide toxicity to bees, analyses of actual doses found in pollen, bees or their honey are below toxic levels. We will investigate whether pesticides, at levels that are sub-toxic by themselves, may synergise with in-hive miticides to alter the brain activity of bees, disrupt their locomotion, ‘higher cognitive function’ (e.g. learning and memory), bee communication or social interaction.


This research brings together a group of scientists with diverse but complimentary expertise in cellular and molecular neuroscience, neuroethology and behavioural ecology. Using a systems biology approach, we are performing a series of integrated interdisciplinary experiments to address these key issues. We are exploring the responses of bees to sub-lethal exposure to miticide/pesticide combinations at multiple levels of organisation: We (Connolly lab) will investigate individual neuronal responses to determine neurotoxicity, sub-lethal neuronal responses such as dendritic beading (movie 1), mitochondrial structural collapse (movie 2) and mitochondrial depolarisation (movie 3) and long term changes to receptor expression. The results of these studies will inform investigations into neurotransmission using fluorescence assays (Connolly lab) and electrophysiology, including plasticity (Harvey lab)

Movie 1 Dendritic beading of a neuron treated with a sub-lethal chemical insult

Movie 2 Mitochondrial collapse and halt to dendritic transport in a neuron treated with a sub-lethal chemical insult

Movie 3 Dendritic beading (blue), mitochondrial collapse (red) and mitochondrial depolarisation (loss of green staining) in a neuron following oxygen-glucose deprivation

Movie 4 Bumblebees (Bombus terrestris) in their nest. Courtesy of Dr Nigel Raine, RHUL

Movie 5 Bumblebees (Bombus terrestris) in a flight arena following training. Courtesy of Dr Nigel Raine, RHUL

(As part of this work Dr Raine will use Radio Frequency Identification tags to monitor bee foraging by record individual bees as they leave and re-enter the nest (Figure 2). A comparison of the difference in the weight of the bee when it returns to the nest, to when it leaves on a subsequent foraging trip, will provide information on the delivery of new resources for the colony.



Figure 2. RFID tagging of bumblebees. Courtesy of Dr Nigel Raine (RHUL)

Movie 6 The waggle dance. Worker bees communicate the location of good food supplies to other workers by dancing in a figure of eight pattern. The direction and duration of the waggle run donotes the direction and distance of the food source. For more information (http://en.wikipedia.org/wiki/Waggle_dance).

Movie 7 "Girl Power" Removal of males (non-workers) from the colony by the females (workers).

Movie 8 Bumblebee colony in laboratory at night.

An important tool for the screening of future agricultural chemicals is the availability of pest species and honeybee cell lines. This aspect of the programme is being conducted at University College London in the lab of Professor Neil Millar

The overall conclusions of this project will be related to the results of the Scottish Beekeepers Association (SBA members’ survey. This will be obtained over a 3-year period to investigate the significance of our findings to the real environment. In particular, SBA will survey, using a large number of honeybee colonies across Scotland, whether particular miticide treatment regimes are detrimental to honeybee health and performance or cause honeybees to become more vulnerable to exposure to other pesticides encountered more sporadically. From this information we hope to correlate the health, productivity and overwintering survivorship of honeybee bee colonies with respect to miticide load and potential pesticide exposure.


Books and chapters

Connolly CN. Protein Trafficking in neurons. In Molecular Biology of the neuron (second edition). Oxford University Press (2004).

Adam J. Vanbergen, Nick Ambrose, David Aston, Jacobus C. Biesmeijer, Andrew Bourke, Tom Breeze, Peter Brotherton, Mike Brown, Dave Chandler, Mark Clook, Christopher N. Connolly, Peter Costigan, Mike Coulson, James Cresswell, Robin Dean, Lynn Dicks, Antonio Felicioli, Otakar Fojt, Nicola Gallai, Elke Genersch, Charles Godfray, Maryanne Grieg-Gran, Andrew Halstead, Debbie Harding, Brian Harris, Chris Hartfield, Matt S. Heard, Barbara Herren, Julie Howarth, Thomas Ings, David Kleijn, Alexandra Klein, William E. Kunin, Gavin Lewis, Alison MacEwen, Christian Maus, Liz McIntosh, Neil S. Millar, Peter Neumann, Jeff Ollerton, Roland Olschewski, Juliet L. Osborne, Robert J. Paxton, Jeff Pettis, Belinda Phillipson, Simon G. Potts, Richard Pywell, Pierre Rasmont, Stuart Roberts, Jean-Michel Salles, Oliver Schweiger, Peter Sima, Helen Thompson, Dalibor Titera, Bernard Vaissiere, Jeroen Van der Sluijs, Sarah Webster, Jonathan Wentworth, Geraldine A. Wright. Insect Pollinators: linking research and policy. UK Science & Innovation Network, Dept. for Business Innovation & Skills. Workshop Report (2012)

Refereed Journal papers


I teach a course on Molecular Neurobiology to 3rd Year Pharmacology & Neuroscience students. This course cuts right across biological boundaries to relate the discovery of genes, how they are regulated, protein biogenesis, function and subcellular targeting and how these impact on neurological diseases. The course then moves into characterising the mechanism of action of disease-causing mutations (e.g. Channelopathies) and finally discusses the future prospects (and problems) of rectifying such genetic faults using gene therapy techniques. The course includes the practical research methods in the study of these processes. In addition, a three week practical is run to compliment the taught lectures. This involves a full project in which the students each work on their own samples within small groups. Currently, this involves screening for the generation of gene mutations (in the lab class) followed by the recombinant expression of the mutant in tissue culture cells and finally fluorescence microscopy to identify the subcellular localisation of the mutant protein. The results of the whole class (several different mutations) are then incorporated into an integrated conclusion. This is the first experience most students have of real research (we don’t know!  As part of the ideology of the course, the assignment in this course offers the opportunity to engage with a primary research paper and an opportunity (optional) to deliver a short talk in public (the whole class).

I also deliver three hour lectures in the final (fourth) honours year on Protein trafficking in synaptic plasticity and mechanisms of neuronal excitotoxicity. I also usually supervise 1-2 lab-based honours student projects each year.

I am external examiner for the Medical Sciences MRes course for Newcastle University that includes programmes on Ageing & Health, Animal Behaviour, Biotechnology & Business Enterprise, Biosciences, Cancer, Epidemiology, Immunology, Medical & Molecular Biosciences, Medical Genetics, Molecular Microbiology, Nanomedicine, Neuroscience, Stems Cells & Regenerative Medicine, Systems Biology, Toxicology, Translational Medicine & Therapeutics and Transplantation.


4th Year: Module leader – “Chemical Stress” and lecture in one 3hr session.

4th Year: One 3 hr lecture in synaptic plasticity module

3rd Year: Three 1 hour lectures on GI tract and joint supervision of 1 practical class


PhD Supervision

Andrew Samson (2017) Spreading neurotoxicity.

Sarah Mizielinska (2009) Rapid neuronal responses to glutamate-induced ecitotoxicity and morphological changes.

Sam Matthew Greenwood (2006). Dynamic changes in neuronal morphology and mitochondrial function during excitotoxicity.




Invited Speaker - 25th Ion Channel Meeting. Oleron Island, France (2014)

Invited speaker – ‘Association of Independent Crop Consultants’ conference Birmingham (January 2011)

Invited speaker – ‘CropWorld 2010’: Are pesticides killing our bees? London (November 2010)

Invited speaker – Annual Symposium of CECHR, Dundee. (2010, 2013, 2015)

Organiser and speaker (Biochemical Society) “Neuronal glutamate and GABAA receptor function in health and disease” St. Andrews University (2009)

Invited speaker ‘Christopher Thompson Memorial Symposium’ (Durham 2008) “Glutamate excitotoxicity”

Invited speaker – European Winter Conference on Brain Research (Switzerland 2007) “GABA(A) receptor biogenesis and trafficking in epilepsy”

Meeting organiser and Chair (Glasgow, Bioscience 2007) “Pharmacological chaperones”

Invited speaker - Serotonin Club (Japan 2006) “The 5-HT3 receptor, from structure to function”

Meeting Chair (Glasgow, Bioscience 2006) “Structure and function of voltage-gated ion channels”

Meeting speaker (Glasgow, Bioscience 2006) “Structure and function of ligand-gated ion channels”

Invited lecturer: Molecular Neuroscience Graduate Course (University of Coimbra, Portugal 2005)

Meeting organiser (Glasgow, Bioscience 2005) “The role of insulin and leptin in cognitive function”

Meeting organiser and Chair (Merck Sharpe Dohme, UK, 2004) “Ligand-gated ion channel structure”

Meeting Chair (Glasgow, Bioscience 2004) “ mRNA trafficking”

Meeting Organiser (Harrogate 2003). “Ligand-gated ion channel biology”. Co-organisers are Prof RAJ McIlhinney (Oxford) and Dr N Millar (UCL).

University Seminar Speaker:

(October 2014) Roslin Institute, Edinburgh.

(January 2013) University of Southampton, Centre for Biological Sciences.

(April 2013) Tufts Medical School, Boston, MA.

(April 2012) St. Andrews University, School of Medical Science.

(October 2011) University of Aberdeen, Institute of Medical Sciences.

(December 2010) Science and Advice for Scottish Agriculture (SASA), Edinburgh

(September 2010) School of Medical Sciences, University of St.Andrews.

(March 2009) Sensory Biology Section, NIDCR, NIH, Bethesda, Washington DC.

(April 2008) Centre for Neuroscience, University of Edinburgh.

(April 2007) Biomedical Sciences, University of Aberdeen

(April 2006) Centre for Integrative Physiology, University of Edinburgh.

(February 2006) Royal College of Surgeons, Dublin.

(July 2005) Institute of Medical Sciences, Aberdeen.

(February 2005)  Biomedical Sciences, University of Durham.

(January 2004) School of Biology, University of St.Andrews.

(January 2003)  IBLS, University of Glasgow.



Impact on policy:
1. Written evidence provided to Environmental Audit Committee (05/02/12).
2. Invitation to provide oral evidence to the UK Parliamentary Select Committee hearing – Insects and pesticides, the Environmental Audit Committee (29/02/12)
3. Invited presentation to Houses of Parliament (MP’s and Lords) on the National Pollinator Strategy (28/10/14). http://www.parliament.uk/documents/post/Nationalpollinatorstrategysummar...
4. Parliamentary PostNote “Protecting insect pollinators from pesticide risk”. Christopher Connolly, Nigel Raine, Geraldine Wright. March 2015.

Impact on Research Funders:
1. ‘Honeybee parasite found in Scotland’
2. ‘Bee brain study reveals pesticide effect’
3. Wellcome News 67, 10-11 (Summer 2011). “How I got into”
4. Wellcome News 66, 28-31 (Spring 2011). “Protecting the Pollinators”
5. BBSRC News: 27th March 2012. http://www.bbsrc.ac.uk/news/food-security/2013/130327-pr-pesticide-combi...
6. BBSRC News: 28th October 2013. http://www.bbsrc.ac.uk/news/food-security/2013/131028-n-bbsrc-helps-scot...  

Impact on Public:
1. IFLScience website coverage or recent publication (Moffat 2015) where it has received 27,700 Facebook Likes
2. BBSRC Sparking Impact Awards. Two awards were funded, both to investigate the risks to bee health. One involved the empowerment of beekeepers to monitor honeybee disease in Scotland. Result was the identification of the spread of a new threat (Nosema ceranae) across Scotland and the identification of a simple microscopic means of monitoring its spread across the globe.
3. Scientific conference on impacts of pesticides on bee health. YouTube video (>1000 views) of discussion between Industry, DEFRA, academia and online audience: https://www.youtube.com/watch?v=6pbCGDWed68

Numerous live and recorded interviews on TV (e.g. French TV channel “France 5” News item. 20th August 2010, STV: 16th September 2011, 9th January 2013 and 19th January 2013, BBC Landward 20th April 2012) and radio (e.g. Radio Tay – 22nd June 2010, Radio 4 “You and Yours” 18th July 2011, Radio 4 “World at One” 31st January 2012, BBC Radio Scotland 3rd February 2015) and many newspaper (national and international) articles about our research.
* Only a selection highlighted from over 100 outputs.