Online supplementary material to
Modulation of septo-hippocampal theta activity
by GABAA receptors: An experimental and
computational approach
Mihaly Hajos1, William E. Hoffmann1, Gergo Orban2,
Tamas Kiss2, Peter Erdi2,3
ABSTRACT of the Neuroscience paper
Theta frequency oscillation of the septo-hippocampal system has been
considered as a prominent activity associated with cognitive function
and affective processes. It is well documented that anxiolytic drugs
diminish septo-hippocampal oscillatory theta activity contributing to
their either therapeutic or unwanted side effects. In the present
experiments we applied a combination of computational and
physiological techniques to explore the functional role of GABAA
receptors in theta oscillation. In electrophysiological experiments
extracellular single unit recordings were performed from medial
septum/diagonal band of Broca (MS/DB) with simultaneous hippocampal
(CA1) EEG recordings from anesthetized rats. Neurotransmission at
GABAA receptors were modulated by means of pharmacological tools: the
actions of the GABAA receptor positive allosteric modulator diazepam
and inverse agonist/negative allosteric modulator FG-7142 were
evaluated on septo-hippocampal activity. Systemic administration of
diazepam inhibited, whereas FG-7142 enhanced theta oscillation of
MS/DB neurons and hippocampal EEG theta activity. In parallel to
these experimental observations, a computational model has been
constructed by implementing a MS/DB GABA neuron model with a
three-neuron population hippocampal CA1 model (including oriens and
basket interneurons and pyramidal cells; each cell type modelled by
multicompartmental techniques). This connectivity made the network
capable of simulating the responses of the septo-hippocampal circuitry
to the modulation of GABAA transmission, and the presently described
computational model proved suitable to reveal several aspects of
pharmacological modulation of GABAA receptors. In addition,
computational findings indicated different roles of distinctively
located GABAA receptors in theta generation.
Purpose of these pages
These pages were created to supply the Reader with details: equations,
parameter ranges, computer simulations scripts used for simulations
published in the article. Scripts are written for the GENESIS simulator
program and are available piece-by-piece from cell description pages
or as a single tarball from the download page.
We suggest to first browse through the given references as they are of great importance
in the understanding of our model. By clicking on different parts of
the image below equations and parameters describing the selected
component of the model are available.
[Pyramidal cell] - [Basket interneuron] - [O-LM interneuron] - [MSGABA interneuron] - [Synaptic Structure] - [References] - [Downloads]
Please send your questions and comments to: Tamas Kiss at bognor@sunserv.kfki.hu
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