Kerr, Michael I. (2013) The role of adenosine in the modulation of synaptic transmission and action potential firing of thick-tufted layer 5 pyramidal neurons. PhD thesis, University of Warwick.

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Abstract

The actions of many neuromodulators induce changes in synaptic transmission and membrane excitability, and many of these effects are well documented in neurons across the CNS. Adenosine acts as a powerful modulator across the CNS and while its actions have been characterised in some neurons in the neocortex, its effects on excitatory transmission in layer 5 remain unstudied. Adenosine has been implicated in the modulation of spontaneous activity generated in the layer 5 excitatory network, thus understanding its actions in this area are of substantial importance.

This study used a combined approach of paired intracellular recordings and quantitative modelling to investigate the actions of adenosine on thick-tufted layer 5 pyramidal neurons in the rat somatosensory cortex.

Adenosine was found to powerfully suppress synaptic transmission between these neurons and the changes in synaptic dynamics could be precisely captured as a change only in probability of release in a simple phenomenological model. Recordings conducted at three post-natal ages provide evidence that an increased tone of endogenous adenosine is responsible for the previously described developmental shift in short-term dynamics and reliability of this synapse. The data illustrates both that this endogenous activation of A1 receptors is highly heterogeneous, with variation between neighbouring synapses, and that it plays a significant role in EPSP parameters observed at mature connections.

An investigation into adenosine's post-synaptic actions using an approach that measures the neurons' I-V response to naturalistic current inputs demonstrates how adenosine's actions on membrane excitability translate to a strong suppression of spiking. Simultaneous dendritic and somatic recordings demonstrate that this effect is enhanced when current is injected from the dendrite and that back-propagating bursts of action potentials are selectively suppressed by adenosine. As a whole the work illustrates that the effects of adenosine can be well captured by mathematically tractable quantitative models.

Item Type:	Thesis or Dissertation (PhD)
Subjects:	Q Science > QP Physiology
Library of Congress Subject Headings (LCSH):	Adenosine, Neural transmission -- Regulation, Computational neuroscience
Official Date:	March 2013
Dates:	Date Event March 2013 Submitted
Institution:	University of Warwick
Theses Department:	Systems Biology Doctoral Training Centre
Thesis Type:	PhD
Publication Status:	Unpublished
Supervisor(s)/Advisor:	Richardson, Magnus J. E.; Wall, Mark
Extent:	xii, 171 leaves : illustrations.
Language:	eng

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