Rasooli-Nejad, Seyed (2014) The role of gliotransmitters in astrocyte-driven modulation of synaptic plasticity in the neocortex. PhD thesis, University of Warwick.

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Abstract

Communication between neuronal and glial cells is important for many brain functions. Astrocytes can modulate synaptic strength by releasing gliotransmitters. The mechanisms underlying release of gliotransmitters remain uncertain with exocytosis being the most intriguing and debated pathway. Furthermore, the contribution of gliotransmitter release to synaptic transmission and plasticity is also debated. Therefore, the purpose of this project was to investigate whether astrocytes can release gliotransmitters via vesicular exocytosis and to investigate the role of this release in synaptic transmission and plasticity in the somatosensory cortex. To investigate this, the transgenic mice line called dnSNARE, where vesicular exocytosis of gliotransmitters is impaired specifically in astrocytes, were used in combination with electrophysiological and pharmacological approaches.

It was shown that cortical astrocytes can release ATP via calcium-dependent vesicular exocytosis. The released astrocytic ATP can bind to neuronal P2X receptors. This results in inhibition of GABAergic transmission. This in turn leads to increase in NMDAR activity during synaptic transmission and plasticity. It was shown that NMDAR-dependent LTP is modulated via vesicular exocytosis of ATP from astrocytes.

It was also shown that astrocytes can release glutamate and D-serine via vesicular exocytosis. However, release of D-serine was not required for LTP induction in the somatosensory cortex. Release of glutamate from astrocytes activated GluN2B-containing NMDARs on cortical neurones. These GluN2B-containing NMDARs contributed to LTP induction in the cortex.

The role of endocannabinoid signalling in synaptic transmission and plasticity was also investigated. It was shown that application of anandamide could result in calcium elevation in astrocytes by acting on CB1 receptors on these cells. This lead to vesicular exocytosis of ATP from astrocytes onto P2X receptors on neurones. This vesicular release of ATP from astrocytes contributed to LTP induction in the somatosensory cortex.

Item Type:	Thesis or Dissertation (PhD)
Subjects:	Q Science > QP Physiology
Library of Congress Subject Headings (LCSH):	Astrocytes, Exocytosis, Neural transmission, Somatosensory cortex
Official Date:	July 2014
Dates:	Date Event July 2014 Submitted
Institution:	University of Warwick
Theses Department:	Systems Biology Doctoral Training Centre
Thesis Type:	PhD
Publication Status:	Unpublished
Supervisor(s)/Advisor:	Pankratov, Yuriy
Extent:	285 leaves : illustrations, charts
Language:	eng

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