Professor Graham Collingridge

Photo of Professor Graham Collingridge

Professor Graham Collingridge

Dorothy Hodgkin Building, Whitson Street, Bristol
BS1 3NY
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g.l.collingridge@bristol.ac.uk

Telephone Number (0117) 331 1913
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Organisations

School of Physiology and Pharmacology

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Plasticity in the Hippocampus

Research overview

The laboratory is interested in synaptic mechanisms and, in particular, synaptic plasticity in the mammalian central nervous system. Synaptic plasticity is the process by which synapses alter their efficiency and this property is used by the nervous system to store information. Synaptic plasticity is therefore a fundamental property of the brain involved in the development of the nervous system, learning & memory and other cognitive processes. Dysfunction of synaptic plastic processes is believed to be involved in various psychiatric and neurological disorders, including epilepsy and ischaemic brain injury. By elucidating the mechanisms of synaptic plasticity at a molecular level we can begin to understand how we are able to learn and remember, and how these processes are altered in conditions such as Alzheimer's Disease, schizophrenia, Parkinson's disease, chronic stress, anxiety, depression and epilepsy.

We are particularly interested in the phenomena of long-term potentiation (LTP) and long-term depression (LTD), which are forms of synaptic plasticity exhibited by many different classes of synapse in the brain. Most of our work focuses on synaptic plasticity in the hippocampus, a brain area important for learning and memory. Within the hippocampus we work on two main synapses, the Schaffer collateral / commissural projection from CA3 to CA1 neurons and the mossy fibre projection from dentate granule cells to CA3 neurons. The main focus of the work we do is to investigate the underlying mechanisms of different forms of LTP and LTD at these synapses using a combination of electrophysiological and imaging techniques.

Key words

Glutamate, GABA, receptor, hippocampus, memory, learning, Long term depression (LTD), long term potentiation (LTP)

Key findings

  • The JAK/STAT pathway has a key role in synaptic plasticity Read more >
  • PICK1 is directly involved in LTP
  • demonstrated the importance of GSK3 in LTD Read more >
  • showed that LTP blocks LTD thus preserving learned information
  • multiple signalling cascades in mGluR-LTD
    Read more >

Diseases related to this field of research

Epilepsy, Alzheimer's Disease, schizophrenia

Processes and functions relevant to this work

Memory and learning, synaptic plasticity

Research group

Mascia Amici, William Anderson, Georgia Culley, Andrew Doherty, Grace France, Marion Mercier, Stephane Peineau, Patrick Tidball, Arturas Volianskis, James Wallis

Techniques in routine use

Electrophysiology, single and multiphoton imaging, molecular biology, slice preparation, field potential recording, intracellular recording, whole cell patch clamp recording

Equipment in routine use

Electrophysiological apparatus, electrode puller, two photon microscope

Collaborations

Principal collaborators in the MRC Centre:
Professor Zafar Bashir, Dr Zuner Bortolotto, Professor Jeremy Henley, Professor David Jane, Professor David Lodge, Professor Elek Molnar, Professor Kei Cho, Professor Stafford Lightman.
In industry:
Eli Lilly and co. Ltd., GlaxoSmithKline

Teaching

I deliver undergraduate lectures in the Neuroscience programme. I supervise / co-supervise graduate PhD students in the MRC Centre.

I deliver undergraduate lectures in the Physiology and Pharmacology programme.

Public engagement

I do many public lectures at such events as the annual BA Festival of Science, visits to local schools and interested organisations. I am a co-founder of the European Dana Alliance for the Brain, an organisation that seeks to promote neuroscience research to a lay public audience.



Key publications

  1. Nicolas, C, Peineau, S, Amici, M, Csaba, Z, Fafouri, A, Javalet, C, Collett, V, Hildebrandt, L, Seaton, G, Choi, S-L, Sim, S-E, Bradley, C, Lee, K, Zhuo, M, Kaang, B-K, Gressens, P, Dournaud, P, Fitzjohn, SM, Bortolotto, Z, Cho, K & Collingridge, G 2012, ‘The JAK/STAT pathway is involved in synaptic plasticity’. Neuron, vol 73., pp. 374 - 390
  2. Kim, JL, Lee, HR, Sim, SE, Baek, J, Yu, NK, Choi, JH, Ko, HG, Lee, YS, Park, SW, Kwak, C, Ahn, SJ, Choi, SY, Kim, H, Kim, KH, Backx, PH, Bradley, CA, Kim, E, Jang, DJ, Lee, K, Kim, SJ, Zhuo, M, Collingridge, G & Kaang, BK 2011, ‘PI3Kγ is required for NMDA receptor-dependent long-term depression and behavioral flexibility’. Nature Neuroscience, vol 14., pp. 1447 - 1454
  3. Li, X, Ko, H, Chen, T, Descalzi, G, Koga, K, Wang, H, Kim, S, Shang, Y, Kwak, C, Park, S, Shim, J, Lee, K, Collingridge, G, Kaang, B & Zhuo, M 2010, ‘Alleviating neuropathic pain hypersensitivity by inhibiting PKMzeta in the anterior cingulate cortex’. Science, vol 330., pp. 1400 - 1404
  4. Collingridge, G, Peineau, S, Howland, J & Wang, Y 2010, ‘Long-term depression in the CNS’. Nature Reviews/Neuroscience, vol 11., pp. 459 - 473
  5. Jo, J, Heon, S, Kim, M, Son, G, Park, Y, Henley, J, Weiss, J, Sheng, M, Collingridge, G & Cho, K 2008, ‘Metabotropic glutamate receptor-mediated LTD involves two interacting Ca(2+) sensors, NCS-1 and PICK1’. Neuron, vol 60., pp. 1095 - 1111

Latest publications

  1. Kimura, T, Whitcomb, DJ, Jo, J, Regan, P, Piers, T, Heo, S, Brown, C, Hashikawa, T, Murayama, M, Seok, H, Sotiropoulos, I, Kim, E, Collingridge, GL, Takashima, A & Cho, K 2014, ‘Microtubule-associated protein tau is essential for long-term depression in the hippocampus’. Philosophical transactions of the Royal Society of London. Series B, Biological sciences, vol 369., pp. 20130144
  2. Yoo, J, Bakes, J, Bradley, C, Collingridge, GL & Kaang, B-K 2014, ‘Shank mutant mice as an animal model of autism’. Philosophical transactions of the Royal Society of London. Series B, Biological sciences, vol 369., pp. 20130143
  3. Park, P, Volianskis, A, Sanderson, TM, Bortolotto, ZA, Jane, DE, Zhuo, M, Kaang, B-K & Collingridge, GL 2014, ‘NMDA receptor-dependent long-term potentiation comprises a family of temporally overlapping forms of synaptic plasticity that are induced by different patterns of stimulation’. Philosophical transactions of the Royal Society of London. Series B, Biological sciences, vol 369., pp. 20130131
  4. Bliss, TVP, Collingridge, GL & Morris, RGM 2014, ‘Synaptic plasticity in health and disease: introduction and overview’. Philosophical transactions of the Royal Society of London. Series B, Biological sciences, vol 369., pp. 20130129
  5. Rocca, DL, Amici, M, Antoniou, A, Suarez, EB, Halemani, N, Murk, K, McGarvey, J, Jaafari, N, Mellor, JR, Collingridge, GL & Hanley, JG 2013, ‘The small GTPase Arf1 modulates Arp2/3-mediated actin polymerization via PICK1 to regulate synaptic plasticity’. Neuron, vol 79., pp. 293-307

Full publications list in the University of Bristol publications system

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