The Library
The role of adenosine in the modulation of synaptic transmission and action potential firing of thick-tufted layer 5 pyramidal neurons
Tools
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.
|
Text
WRAP_THESIS_Kerr_2013.pdf - Submitted Version Download (12Mb) | Preview |
Official URL: http://webcat.warwick.ac.uk/record=b2689298~S
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 (PhD) | ||||
---|---|---|---|---|---|
Subjects: | Q Science > QP Physiology | ||||
Library of Congress Subject Headings (LCSH): | Adenosine, Neural transmission -- Regulation, Computational neuroscience | ||||
Official Date: | March 2013 | ||||
Dates: |
|
||||
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 |
Request changes or add full text files to a record
Repository staff actions (login required)
View Item |
Downloads
Downloads per month over past year