Modulation of septo-hippocampal θ activity by GABAA receptors: An experimental and computational approach

M. Hajós, W. E. Hoffmann, G. Orbán, T. Kiss, P. Érdi

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

θ 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 θ 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 θ oscillation. In electrophysiological experiments extracellular single unit recordings were performed from medial septum/diagonal band of Broca with simultaneous hippocampal (CA1) electroencephalogram (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 θ oscillation of septal neurons and hippocampal EEG θ activity. In parallel to these experimental observations, a computational model has been constructed by implementing a septal GABA neuron model with a CA1 hippocampal model containing three types of neurons (including oriens and basket interneurons and pyramidal cells; latter modeled by multicompartmental techniques; for detailed model description with network parameters see online addendum: http://geza.kzoo.edu/theta). 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 θ generation.

Original languageEnglish
Pages (from-to)599-610
Number of pages12
JournalNeuroscience
Volume126
Issue number3
DOIs
Publication statusPublished - 2004

Fingerprint

GABA-A Receptors
Diazepam
Electroencephalography
Diagonal Band of Broca
Pharmacology
Neurons
GABAergic Neurons
Pyramidal Cells
Anti-Anxiety Agents
Interneurons
Synaptic Transmission
Cognition
Pharmaceutical Preparations
FG 7142

Keywords

  • A-type potassium current
  • allosteric modulators
  • anxiety
  • delayed rectifier potassium current
  • EEG
  • electroencephalogram
  • hippocampus
  • I
  • I
  • I
  • I
  • medial septum
  • sodium current

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Modulation of septo-hippocampal θ activity by GABAA receptors : An experimental and computational approach. / Hajós, M.; Hoffmann, W. E.; Orbán, G.; Kiss, T.; Érdi, P.

In: Neuroscience, Vol. 126, No. 3, 2004, p. 599-610.

Research output: Contribution to journalArticle

Hajós, M. ; Hoffmann, W. E. ; Orbán, G. ; Kiss, T. ; Érdi, P. / Modulation of septo-hippocampal θ activity by GABAA receptors : An experimental and computational approach. In: Neuroscience. 2004 ; Vol. 126, No. 3. pp. 599-610.
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