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Professor Graham Collingridge

Plasticity in the Hippocampus

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.

Research keywords

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

Diseases related to this field of research

  • Epilepsy
  • Alzheimer's Disease
  • schizophrenia

Processes and functions relevant to this work

  • Memory and learning
  • synaptic plasticity

Equipment relevant to this work

  • Electrophysiological apparatus
  • electrode puller
  • two photon microscope

Research 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 >

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