umu.sePublications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Differential control of spontaneous and evoked GABA release by presynaptic L-type Ca2+ channels in the rat medial preoptic nucleus
Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
(English)Manuscript (preprint) (Other academic)
Abstract [en]

To clarify the role of presynaptic L-type Ca2+ channels in GABA-mediated transmission in the medial preoptic nucleus (MPN), spontaneous as well as impulse-evoked inhibitory postsynaptic currents (sIPSCs and eIPSCs, respectively) were recorded from MPN neurons in a slice preparation from rat brain. The effects of different stimulus protocols and pharmacological tools to detect contributions of L-type Ca2+ channels and of Ca2+-activated K+ (KCa) channels were analysed. Block of L-type channels did not affect the sIPSCs properties (frequency, amplitude, decay time course) in the absence of external stimulation, but unexpectedly potentiated the eIPSCs evoked at low stimulus frequency (0.1 – 2.0 Hz). This effect was similar to and overlapping with the effect of KCa-channel blockers. High-frequency stimulation (50 Hz for 10 s) induced a substantial post-tetanic potentiation (PTP) of the eIPSC amplitude as well as of the sIPSC frequency. Block of L-type channels still potentiated the eIPSC during PTP, but in contrast reduced the sIPSC frequency during PTP. It was concluded that L-type channels provide a means for differential control of spontaneous and impulse-evoked GABA release and that this differential control is prominent during short-term synaptic plasticity. Functional coupling of the presynaptic L-type channels to KCa channels explains the observed effects on eIPSCs.

Keyword [en]
L-type Ca2+ channel, GABA release, synaptic plasticity, post-tetanic potentiation, medial preoptic nucleus
National Category
Physiology
Research subject
Physiology
Identifiers
URN: urn:nbn:se:umu:diva-25870OAI: oai:DiVA.org:umu-25870DiVA: diva2:234471
Available from: 2009-09-08 Created: 2009-09-08 Last updated: 2011-04-07Bibliographically approved
In thesis
1. Neurotransmission and functional synaptic plasticity in the rat medial preoptic nucleus
Open this publication in new window or tab >>Neurotransmission and functional synaptic plasticity in the rat medial preoptic nucleus
2009 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Brain function implies complex information processing in neuronal circuits, critically dependent on the molecular machinery that enables signal transmission across synaptic contacts between neurons. The types of ion channels and receptors in the neuronal membranes vary with neuron types and brain regions and determine whether neuronal responses will be excitatory or inhibitory and often allow for functional synaptic plasticity which is thought to be the basis for much of the adaptability of the nervous system and for our ability to learn and store memories. The present thesis is a study of synaptic transmission in the medial preoptic nucleus (MPN), a regulatory center for several homeostatic functions but with most clearly established roles in reproductive behaviour. The latter behaviour typically shows several distinct phases with dramatically varying neuronal impulse activity and is also subject to experience-dependent modifications. It seems likely that the synapses in the MPN contribute to the behaviour by means of activity-dependent functional plasticity. Synaptic transmission in the MPN, however, has not been extensively studied and is not well understood. The present work was initiated to clarify the synaptic properties in the MPN. The aim was to achieve a better understanding of the functional properties of the MPN, but also to obtain information on the functional roles of ion channel types for neurotransmission and its plastic properties in general. The studies were carried out using a brain slice preparation from rat as well as acutely isolated neurons with adhering nerve terminals. Presynaptic nerve fibres were stimulated electrically or, in a few cases, by raised external K+ concentration, and postsynaptic responses were recorded by tight-seal perforated-patch techniques, often combined with voltage-clamp control of the post-synaptic membrane potential. Glutamate receptors of α-amino-3-hydroxy-5-methyl-4-izoxazole propionic acid (AMPA) and N-methyl-D-aspartate (NMDA) types were identified as mediating the main excitatory synaptic signals and γ-aminobutyric acid (GABA)A receptors as mediating the main inhibitory signals. Both types of signals were suppressed by serotonin. The efficacy of AMPA-receptor-mediated transmission displayed several types of short-term plasticity, including paired-pulse potentiation and paired-pulse depression, depending on the stimulus rate and pattern. The observed plasticity was attributed to mainly presynaptic mechanisms. To clarify some of the presynaptic factors controlling synaptic efficacy, the role of presynaptic L-type Ca2+ channels, usually assumed not to directly control transmitter release, was investigated. The analysis showed that (i) L-type channels are present in GABA-containing presynaptic terminals on MPN neurons, (ii) that these channels provide a means for differential control of spontaneous and impulse-evoked GABA release and (iii) that this differential control is prominent during short-term synaptic plasticity. A model where Ca2+ influx through L-type channels may lead to reduced GABA release via effects on Ca2+-activated K+ channels, membrane potential and other Ca2+-channel types explains the observed findings. In addition, massive Ca2+ influx through L-type channels during high-frequency stimulation may contribute to increased GABA release during post-tetanic potentiation. In conclusion, the findings obtained in the present study indicate that complex neurotransmission mechanisms and different forms of synaptic plasticity contribute to the specific functional properties of the MPN.

Place, publisher, year, edition, pages
Umeå: IMB, 2009. 57 p.
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 1286
Keyword
medial preoptic nucleus, synaptic plasticity, GABA, glutamate, L-type Ca2+ channel
National Category
Physiology
Research subject
Physiology
Identifiers
urn:nbn:se:umu:diva-25874 (URN)978-91-7264-843-2 (ISBN)
Distributor:
Fysiologi, 901 87, Umeå
Public defence
2009-09-30, Hörsal KB3A9, Umeå Universitet, Umeå, 10:00 (English)
Opponent
Supervisors
Available from: 2009-09-10 Created: 2009-09-08 Last updated: 2010-01-18Bibliographically approved

Open Access in DiVA

No full text

Search in DiVA

By author/editor
Druzin, MichaelJohansson, Staffan
By organisation
Physiology
Physiology

Search outside of DiVA

GoogleGoogle Scholar

urn-nbn

Altmetric score

urn-nbn
Total: 36 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf