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Aminergic regulation of neuronal synchrony in the hippocampus

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posted on 2024-09-03, 03:40 authored by Richard Andersson

Background: Gamma oscillations (25-80 Hz) are physiological electric activity patterns, prevalent in the brain, which are associated with attention, working memory, sensory perception, long-term memory encoding and recall. Importantly, in mental illnesses featuring cognitive disturbances (such as Schizophrenia or Alzheimer’s disease) there are concomitant disturbances of gamma oscillations. All aspects of cognitive function are regulated by the aminergic systems of the brain, which are also associated with mental disorders. Yet little research has been done to understand how aminergic molecules modulate or control gamma oscillations.

Aims: We aimed to investigate whether gamma oscillations are modulated by aminergic G-protein-coupled receptors. We also wanted to determine which types of neurons and circuitry mechanisms are responsible for any aminergic effects uncovered.

Methods: We used an in vitro preparation of the rodent hippocampus in which stable gamma oscillations were elicited by the application of kainic acid. Combined extracellular local field potential and intracellular patch clamp recordings were used to reveal which network, synaptic and cellular parameters changed in response to various pharmacolog- ical challenges.

Results & Conclusions: We found that it is possible to bi-directionally regulate gamma oscillations in the hippocampus, without affecting the overall firing- rate of action potentials. Rather, it is the phase-synchronization of pyramidal cell and fast-spiking interneuron activity that is affected by histamine H3 and dopamine D4 receptors, respectively. This is a potential physiological mechanism by which the gain of signal transmission to downstream targets can be regulated. Targeting this mechanism may have a potential use in future antipsychotic or pro- cognitive pharmaceutical therapy.

List of scientific papers

I. Histamine H3 receptor activation decreases kainate-induced hippocampal gamma oscillations in vitro by action potential desynchronization in pyramidal neurons. (2010) Andersson R., Lindskog M. and Fisahn A. Journal of Physiology. (588): 1241-9.
https://doi.org/10.1113/jphysiol.2009.180984

II. Neuregulin and dopamine modulation of hippocampal gamma oscillations is dependent on dopamine D4 receptors. (2012) Andersson R., Johnston A., Herman P., Winzer-Serhan U., Karavanova I, Vullhorst D., Fisahn A., and Buonanno A. Proceedings of the National Academy of Science. (109)32: 13118-23.
https://doi.org/10.1073/pnas.1201011109

III. Dopamine D4 Receptor Activation Increases Hippocampal Gamma Oscillations by Enhancing Synchronization of Fast-Spiking Interneurons. (2012) Andersson R., Johnston A. and Fisahn A. PLoS ONE. (7)7: e40906.
https://doi.org/10.1371/journal.pone.0040906

History

Defence date

2012-10-26

Department

  • Department of Neurobiology, Care Sciences and Society

Publisher/Institution

Karolinska Institutet

Main supervisor

Fisahn, André

Publication year

2012

Thesis type

  • Doctoral thesis

ISBN

978-91-7457-884-3

Number of supporting papers

3

Language

  • eng

Original publication date

2012-10-03

Author name in thesis

Andersson, Richard

Original department name

Department of Neurobiology, Care Sciences and Society

Place of publication

Stockholm

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