FRS FMedSci

Department of Pharmacology, Oxford Neuroscience,
University of Oxford, UK

Title of seminar

"Exploration of cortical GABAergic neuronal diversity with Marco Capogna"

Abstract

The function of any given cortical area is delivered by long-range glutamatergic neuronal outputs in co-operation with other parts of the nervous system. The activity of the glutamatergic neurons in any given area is shaped by more than 50 distinct local and some long-range GABAergic neuronal types, each specialising in affecting different cortical space and acting with distinct temporal dynamics.  The action of each GABAergic neuronal type is supported by evolution-selected molecular mechanisms. I had the privilege to explore this diversity with Marco Capogna and other colleagues over decades at Oxford and marvel at the beauty of the neuronal diversity reflected in their spatio-temporal features. I will focus on two contrasting neuronal types, to the understanding of which Marco made seminal contributions. The the axo-axonic cell selectively innervates only the axon-initial segment of glutamatergic neurons, acts through GABA-A receptors and has profound influence on their firing. The neurogliaform cell in contrast, provides a uniquely dense, small axonal cloud influencing all neuronal processes through both synapses and by volume conduction acting through both GABA-A and GABA-B receptors. Both cell types participate in cortical function in all cortical areas including the hippocampal formation and the amygdala. The journey of exploration has been exciting and will continue long beyond our contributions and is already taken to new heights by some of our colleagues and students. I hope that one day the roles of each cell type will be explained in the context of a unified cortical spatio-temporal dynamic framework governing behaviour.

Read more about Peter Somogyi's research

Institute of Pharmacology,
Medical University of Innsbruck,
Austria

 

Title of seminar

"Neural circuits mediating the influence of metabotropic glutamate receptor 5 on anxiety"
 

Abstract

Anxiety disorders are highly prevalent psychiatric illnesses posing an important social and economic burden. Their current pharmacotherapy shows limited efficacy with more than one third of patients being poorly responsive or therapy resistant. There is, therefore, a strong medical need for new therapeutic agents acting through novel mechanisms of action. Recent preclinical and clinical studies have opened new prospects for targeting metabotropic glutamate (mGlu) receptors as novel anxiolytics. In my talk, I will present new data on how (mechanisms) and where (neural circuits) mGlu5 receptor antagonists impact the negative valence domain. Circuits and mechanisms underlying the anxiolytic-like effect in mice of mGlu5 receptor negative allosteric modulators (NAM) and benzodiazepines (BZD) will also be compared. Our work reveals important operational differences between BZD and mGlu5-NAM in their acute anxiolytic-like effects, that may open new therapeutic avenues.

Read more about Francesco Ferraguti's research