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Epilepsies of the temporal lobe: emergence,
basal state and paroxysmal transitions

Objective

This proposal focuses on a human disease: epilepsy of the temporal lobe. This syndrome has a relatively stereotyped history. Focal seizures emerge, with a delay of several years in the human, after an initial insult that results in neuronal death. We will use physiology, imaging, anatomy and transcriptomic techniques to ask how an epileptic brain emerges, to define different neuronal cell types in the basal epileptic state and to examine factors associated with the paroxysmal transition to a seizure. Specifically we will ask whether a loss of cholesterol homeostasis is involved in the initial sclerotic neuronal death. We will ask whether proteoglycans deposited in the extracellular space as a generalised wound healing response force the establishment of aberrant synaptic contacts and so facilitate the slow process of epileptogenesis. We will then study the basal state of an epileptic brain. We will establish the physiology, anatomy, connectivity and transcriptome of functionally distinct neurons defined by different contributions to epileptiform activities in human epileptic brain slices. Finally we will seek to establish what sudden changes in field potential, ionic homeostasis, cellular firing and synaptic interactions are associated with the paroxysmal moment of transition to seizure.

Field of science

  • /medical and health sciences/basic medicine/physiology/homeostasis
  • /medical and health sciences/basic medicine/neurology/epilepsy
  • /humanities/history and archaeology/history
  • /medical and health sciences/basic medicine/physiology

Call for proposal

ERC-2012-ADG_20120314
See other projects for this call

Funding Scheme

ERC-AG - ERC Advanced Grant

Host institution

INSTITUT DU CERVEAU ET DE LA MOELLE EPINIERE
Address
Boulevard De L'hopital 47
75013 Paris
France
Activity type
Research Organisations
EU contribution
€ 1 985 057
Principal investigator
Richard Miles (Dr.)
Administrative Contact
Alexandra Auffret (Dr.)

Beneficiaries (1)

INSTITUT DU CERVEAU ET DE LA MOELLE EPINIERE
France
EU contribution
€ 1 985 057
Address
Boulevard De L'hopital 47
75013 Paris
Activity type
Research Organisations
Principal investigator
Richard Miles (Dr.)
Administrative Contact
Alexandra Auffret (Dr.)