Christopher Connolly

+44 (0)1382 383105
Reader in Neurobiology & Associate Director of CECHR


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)


This laboratory is interested in the role of ligand-gated ion channel biology and neuronal function in the control of excitation/inhibition in individual neurons, glia and whole neuronal networks. In the past, our studies concentrated on the biogenesis and chronic modulation of ligand-gated ion channel (GABAA and 5-HT3 receptors) function by intracellular trafficking. Our current focus is on excitatory receptors (glutmatergic and nicotinic) and their impact on network level dysfunction and plasticity during chronic exposure to sublethal stimuli. One major research interest is on the role of NMDA receptors in neuronal network dysfunction and resilience, to gain insight into mechanisms relevant to ischaemia, neurodegenerative diseases and epilepsy. Secondly, we are interested in pesticide toxicity to the nervous system of humans and insects. In particular, we are interested in how sublethal chronic exposure may lead to neural adaptations that alter neuronal resilience to further exposure.

Neuronal network responses to insults.

Neuronal changes following exposure to glutamate (sublethal or lethal) include dendritic beading (video 1), mitochondrial arrest in traffic (videos 2a/b) and mitochondrial collapse/depolarisation (Video 3). In addition, we have also found alteration to the cytoskeleton, axonal initial segment location, synaptic connections and neurotransmitter release (not shown).

Dendritic beading. Hippocampal neurons expressing CFP exposed to glutamate.

After the initial competition between neurons to win a place in a developing network, the winners gain from a homeostatic neuroprotection that is maintained by network activity. This is essentially a protection racket and any failure to contribute would be a death sentence to the neuron and a risk to the entire network. However, being a member of this network comes with new activity-dependent risks, such as hyperactivation or inactivation, that may manifest as epileptic seizures or migraine, respectively.

Hyperactivity may be life-threatening to the neuron (and glia), the network and the organism. Neurons are highly active, and so hungry, cells that transport high levels of ions across their membranes in the process of neuronal communication. This make neurons highly dependent on an energy source (glucose) and oxygen, both being delivered by the blood. When this supply is disrupted by a blood clot, the brain region most effected may die quickly. The same may happen following a physical injury. This site is called the lesion and there is little opportunity to save this area. Beyond this lesion site is the surrounding area that is at risk from a partial loss in oxygen/glucose and secondary damage that spreads from the lesion. Spreading toxicity may take two forms – rapid hyperactivity and delayed excitotoxicity from glutamate released from dead/dying cells. In video 3, we demonstrate the morphological consequences of spreading toxicity initiated by oxygen-glucose deprivation. Spreading cell death is coincident with dendritic beading (blue), mitochondrial collapse (red) and mitochondrial dysfunction (loss of green).

Spreading toxicity. Hippocampal neurons transfected with CFP and mito-Red and loaded with Rhodamine123 (green). Upon oxygen-glucose deprivation, spreading toxicity leads to dendritic beading (blue), mitochondrial collapse (red) and mitochondrial depolarisation (loss of green).

This spreading toxicity is reminiscent of a nuclear explosion, where the site of the explosion is wiped out and immediate shock waves spread damage away from this site. Next comes the radioactive cloud, spreading toxicity further. In the case of a brain lesion, the prospects are worse, as the damage should be self-perpetuating – cell dysfunction/death contributing to further release of excitotoxic levels of glutamate on to surrounding cells. Therefore, the entire neuronal network should succumb to toxicity. But this doesn’t happen. Why not?

Microfluidic model of neural network

To study neuronal network behaviour, in collaboration with and engineer (Dr. Michele Zagnoni, University of Strathclyde), we have developed a microfluidic platform for the study of spreading toxicity (Figure 1). These devices have enabled us to perform carefully-controlled studies on the impact of a local insult on a whole network for the first time. Importantly, the model allows that a local insult can be contained within a single chamber and any consequential spread of glutamate is prevented by microfluidic control of each chamber to ensure no diffusion from the insulted chamber to downstream naïve parts of the network occurs. Using this approach, we have been able to isolate activity-dependent spreading toxicity (synaptic toxicity) from secondary excitotoxicity (Figure 2).

Figure 1. Microfluidic device. A five-chambered device in which isolated populations of neurons are separated by narrow microchannels through which axons could pass but neurons could not. A) Chambers filled with different dyes to demonstrate the fluidic independence of each chamber. B) Five chambers shown, with magnification of the microchannel area (C). A localised insult may be delivered to any chamber and its consequences on downstream networks studied.

Figure 2. Spreading toxicity along a network. Top panels) An excitotoxic insult delivered to the central chamber causes high level local toxicity (indicating dead cells (Hoechst, red) versus live cells (DAPI, blue). Central panel) Toxicity spreads downstream, in both directions, by an activity-dependent process (blocked by tetrodotoxin). Lower panel) In addition to spreading toxicity, dendritic beading is observed to spread along the network.

In addition, to spreading toxicity, we discovered that the network was also capable of sending neuroprotective signals rapidly along the network. For example, when a subtoxic insult is presented to the ‘insult’ chamber just before the delivery of an excitotoxic insult to all chambers, no protection is observed in the insulted chamber (Figure 3A). This is expected as protection from sublethal stimuli (preconditioning) requires about 24 hours to be effective. However, immediate protection against an excitotoxic insult is conferred to downstream neurons in the network (Figure 3A). This neuroprotective signal is communicated between neurons (it is activity-dependent, being blocked by tetrodotoxin). This is surprising and important as this indicates that spreading toxicity is limited by homeostatic mechanism. Moreover, if a neuroprotective signal could be delivered quickly by some external device, the damage from a stroke might be blocked quickly, on a time-scale that is relevant to these clinical emergencies (eg. stroke/traumatic brain injury). Interestingly, an excitotoxic insult is also capable of spreading network protection (Figure 3B) suggesting that this is a natural response that we might be able to augment therapeutically.

Perhaps the evolution of a network, with this new vulnerability to spreading toxicity, required the co-evolution of this homeostatic protection that would otherwise wipe out entire networks each time it encountered a challenge? It will be interesting to investigate whether such innate protective mechanisms become compromised during ageing or disease. Our current research is investigating the role of the observed morphological responses to an insult as potential biomarkers of toxicity and neuroprotection, and we are performing a proteomic analysis of the molecular changes that underlie this fast onset neuroprotection.

Figure 3. Spreading protection along a network. Hippocampal neuronal networks can transmit a neuroprotective signal along a network from a sublethal (A, grey arrowhead) or an excitotoxic(B, black arrowhead) insult. This neuroprotection is established much faster (<30 min) than normal preconditioning (~24 hrs), but its effects are transient (<4 hrs) and requires neurotransmission for its spread.

Impact of pesticides on the nervous system of bees

Insect pollinator decline has been identified as a major world problem and is estimated to contribute > £440M to the UK economy every year and is 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 the neuroactive miticides. In addition, all insect pollinators are exposed to an industrialised programme of crop management where >32 million Kg of chemicals were used annually before 2005. This level has decreased to 18 million Kg (2015), but this does not account for the switch to higher potency pesticides. Together, this large amount. And diversity of (~700 chemicals available globally), of chemical exposure creates a highly complex environment where the chronic impact of individual chemicals, and the enormous potential for chemical cocktail effects, may be contributing to our insect pollinator decline and the incidence of chronic idiopathic diseases in man.

The key bee species that are used as managed pollinators include the honeybees (video 4) and the bumblebees (video 5), but many solitary bees also contribute to pollination. The targets for neuroactive insecticides include action potential firing (sodium channels) and the balance between excitatory (cholinergic signalling) and inhibitory (GABA and glutamate-gated chloride channels) neurotransmission (Figure 4). Perturbation of these pathways disrupts brain function in all animals, leading to locomotor, behavioural or social problems. The insect brain structure that is involved in bee learning (olfactory and visual) is the mushroom body and cholinergic neurotransmission providing the major excitatory drive. Neural network stimulation is 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.

Honeybees on a hive frame.

Bumblebees in the nest.

Figure 4. Pesticide targets in the insect nervous system. Chemicals labelled red are anti—varroa chemicals used in honeybee hives, those in green are pesticides.

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/desensitisation. Some neonicotinoids are more resistant to cytochrome P450 detoxicification, or generate toxic metabolites.

Current safety testing of pesticides for effects on bees is limited to their acute effects over a few days, but little is known about the chronic effects of the neonicotinoids on bees. In the field, bees are exposed to neonicotinoids following their application to the soil (either directly or following release from treated seeds), whereupon they are absorbed by plant roots and translocate throughout the plant, including the nectar and pollen collected by bees (Video 6). This is important as exposure to neonicotinoids occurs acutely, via treated crops, but also chronically by secondary exposure from wildflowers and other crops. Therefore, an understanding of the risk from chronic dietary exposure is required.

Bumblebees gathering nectar and pollen from Globe artichoke.

When honeybee brains are exposed to field-realistic levels of organophosphates or neonicotinoids, a biphasic response is seen (Figure 5). An initial increase in neuronal depolarisation is coincident with the firing of action potentials. However, if the exposure continues, the depolarisation ultimately occludes the ability for neurons to fire action potentials, making brain neurons functionally inactive. To examine more chronic exposure (over days), we examined bumblebee Kenyon cell neurons in culture for mitochondrial membrane potential changes as an indicator of neuronal stress (Figure 6).

Figure 5. Honeybee Kenyon cell responses to cholinergic pesticides. A) Exposure to an organophosphate (OP), coumaphos oxon. Exposure to the OP leads to a gradual increase depolarisation as endogenously released acetylcholine levels increase. This leads to a transient hyperactivation, followed by a lack of neuronal responses. B) Exposure to the neonicotinoid, clothianidin. A rapid depolarisation initiates the firing of action potential, which again leads to neuronal inactivation.

Neurons exposed chronically (2 days) to their normal neurotransmitter, acetylcholine (100 mM), did not develop an increased vulnerability to a subsequent exposure of acetylcholine (100 mM). In contrast, neurons exposed to the sublethal (and field-realistic levels that reach the bee brain) level of imidacloprid (1 nM) for 2 days revealed a subpopulation of neurons that were highly sensitive to acetylcholine (100 mM), causing mitochondrial depolarisation immediately, or after a short delay (~10 min). This chronic sensitisation state was blocked by the nAChR antagonist, tubocurarine (500 mM).


Figure 6. Chronic exposure of bumblebee Kenyon cells to imidacloprid leads to sensitisation. Neurons in culture were exposed chronically to either (A) acetylcholine (100 mM) or (B) imidacloprid (1 nM) for 2 days, then neurons allowed to recover prior to exposure to acetylcholine (100 mM). Neurons exposed to imidacloprid, but not acetylcholine, became vulnerable to subsequent chronic exposure to acetylcholine (100 mM).

Within arable environments, bees are exposed to not just a single neonicotinoid, but often multiple different neonicotinoids. Therefore, we assessed the potential for cross-sensitisation to different neonicotinoids. To address whether a low level chronic exposure to neonicotinoids (at field relevant doses (10 nM) for 7 days), lead to an increase vulnerability to a sub-toxic level of clothianidin (200 nM, 50 ppb). Bees exposed imidacloprid, or left untreated, exhibited the same vulnerability to 200 nM clothiandin (Figure 7). In contrast, for bees exposed to low levels of thiamethoxam or clothiandin, their subsequent vulnerability to clothianidin had increased significantly. Therefore, a chronic sensitisation of bees to neonicotinoids occurs following chronic exposure to field-relevant levels. The impact of chronic sensitisation on bees can be seen in Video 7. Moreover, this finding demonstrates that each neonicotinoid needs to be considered separately, with our evidence from semi-field trials indicates that imidacloprid and thiamethoxam are toxic to bumblebee colonies, but clothiandin is not (Figure 8).

Figure 7. Chronic sensitization of bumblebees. Chronic exposure to field-realistic levels of thiamethoxam or clothianidin leads to their increased vulnerability to a high dose of clothianidin. In contrast, imidacloprid-exposed bees did not demonstrate increased vulnerability to clothianidin.

Bumblebees previous exposed to neonicotinoids become more vulnerable. Bees exposed to 10 nM of thiamethoxam (left), clothianidin (right) or imidacloprid (middle) for 7 days prior to exposure to 200 nM clothianidin for 1 day. Bee activity is normal in imidacloprid-exposed bees, but not in those previously exposed to thiamethoxam or clothianidin.

Figure 8. Semi-field trail of bumblebee colonies fed neonicotinoids. Bumblebee colonies (75 colonies) were provided 10 nM neonicotinoid-treated sugar syrup and were placed at 5 different sites across Scotland for 5 weeks where they must forage for pollen (not provided). After this period, colonies were collected and analysed for the number of live bees, live brood cells and number of queens (other information also gathered but not shown here). Each dot represents an individual colony and the bar represents the average obtained. Imidacloprid and thiamethoxam, but not clothianidin, had a detrimental impact on colony growth.

Threats to bees in Scotland (2012-2017).

Our current research interests are in applying basic pharmacological principles to understand the risk from chronic exposure to pesticides (in particular, those targeting cholinergic signaling) and how the damage may be mitigated. For further information on our public engagement activities with Scottish beekeepers and our assessment of the key risks to bees in Scotland, a lay article discussing our studies over the past 6 years can be found here: e7982b47-b1a1-4476-b47b-4d8e8291dc09.


Please click on the link below to view Chris' recent blog: The Biochemist blog: Environmental pharmacology: how safe is our chemical jungle?

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.


Group members

  • Mr. Andrew Samson

Lectures and conferences

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),+the+Environmental+Audit+Committee
3. Invited presentation to Houses of Parliament (MP’s and Lords) on the National Pollinator Strategy (28/10/14).
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.
6. BBSRC News: 28th October 2013.

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:

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.


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


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