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Neurotransmission and functional synaptic plasticity in the rat medial preoptic nucleus
Umeå University, Faculty of Medicine, Integrative Medical Biology, Physiology.
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 [en]
medial preoptic nucleus, synaptic plasticity, GABA, glutamate, L-type Ca2+ channel
National Category
Physiology
Research subject
Physiology
Identifiers
URN: urn:nbn:se:umu:diva-25874ISBN: 978-91-7264-843-2 (print)OAI: oai:DiVA.org:umu-25874DiVA: diva2:234488
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
List of papers
1. Fast neurotransmission in the rat medial preoptic nucleus.
Open this publication in new window or tab >>Fast neurotransmission in the rat medial preoptic nucleus.
2005 (English)In: Brain Research, ISSN 0006-8993, Vol. 1040, no 1-2, 157-68 p.Article in journal (Refereed) Published
Abstract [en]

The functional properties of neurotransmission in the medial preoptic nucleus (MPN) were studied in a brain slice preparation from young male rats. The aims were to evaluate the thin slice preparation for studying evoked synaptic responses in MPN neurons, to characterize the fast responses triggered by activation of presynaptic nerve fibers in the MPN, and to identify the involved receptor types. Presynaptic stimulation within the MPN evoked postsynaptic voltage and current responses that were blocked by 200 microM Cd2+ or by 2.0 microM tetrodotoxin and were attributed to action potential-evoked transmitter release. The relation to stimulus strength and comparison with spontaneous synaptic currents suggested that in many cases only one presynaptic nerve fiber was excited by the stimulus. Furthermore, the transmission was probabilistic in nature, with frequent failures. Thus, response probability, most likely reflecting transmitter release probability, could be evaluated in the thin slice preparation. Evoked excitatory postsynaptic currents recorded under voltage-clamp conditions were, due to kinetics, I-V relation, and pharmacological properties, attributed to AMPA/kainate receptors and NMDA receptors, whereas inhibitory currents were attributed to GABAA receptors. No responses that could be attributed to glycine or other types of primary transmitters were detected. Although serotonin (5-HT) did not appear to function as a primary transmitter, glutamate- as well as GABA-mediated transmission was suppressed by 500 microM 5-HT, with a clear reduction in response probability observed. 5-HT also reduced the frequency, but not the amplitude, of spontaneous postsynaptic currents and was therefore ascribed a presynaptic site of action.

Keyword
Animals, Dizocilpine Maleate/pharmacology, Preoptic Area/drug effects/*physiology, Quinoxalines/pharmacology, Rats, Rats; Sprague-Dawley, Synaptic Transmission/drug effects/*physiology
Identifiers
urn:nbn:se:umu:diva-12595 (URN)doi:10.1016/j.brainres.2005.01.094 (DOI)15804437 (PubMedID)
Available from: 2008-01-11 Created: 2008-01-11 Last updated: 2011-01-12Bibliographically approved
2. Short-term plasticity in excitatory synapses of the rat medial preoptic nucleus.
Open this publication in new window or tab >>Short-term plasticity in excitatory synapses of the rat medial preoptic nucleus.
2006 (English)In: Brain Research, ISSN 0006-8993, Vol. 1110, no 1, 128-35 p.Article in journal (Refereed) Published
Abstract [en]

The medial preoptic nucleus (MPN) regulates sexual behavior which is subject to experience-dependent modifications. Such modifications must depend on functional plasticity in the controlling neural circuits. Thus, MPN synapses are likely candidates for the site of alterations. The present work is a first systematic study of functional synaptic plasticity at glutamatergic synapses in the MPN. Short-term activity-dependent plasticity was investigated using a slice preparation from young male rats. The average efficacy of AMPA/kainate-receptor-mediated synaptic transmission was activity-dependent, showing a peak at a steady stimulation rate of 2 Hz. The variation in efficacy was attributed to mainly presynaptic factors since the average response amplitude was roughly paralleled by the response probability. Upon paired-pulse stimulation, paired-pulse facilitation as well as paired-pulse depression was observed. In some cases, paired-pulse facilitation as well as paired-pulse depression was recorded from an individual neuron depending on the interval between the paired stimuli. On average, paired-pulse facilitation was observed at intervals <500 ms, and paired-pulse depression at intervals in the range 1-4 s. The findings thus reveal complex activity-dependent short-term plasticity of the functional synaptic properties in the medial preoptic nucleus.

Keyword
Animals, Dose-Response Relationship; Radiation, Electric Stimulation/methods, Excitatory Postsynaptic Potentials/*physiology/radiation effects, Neuronal Plasticity/*physiology, Preoptic Area/*cytology, Rats, Rats; Sprague-Dawley, Synapses/*physiology, Time Factors
Identifiers
urn:nbn:se:umu:diva-12593 (URN)doi:10.1016/j.brainres.2006.06.061 (DOI)16870159 (PubMedID)
Available from: 2008-01-11 Created: 2008-01-11 Last updated: 2011-01-11Bibliographically approved
3. Dual and opposing roles of presynaptic Ca2+ influx for spontaneous GABA release from rat medial preoptic nerve terminals
Open this publication in new window or tab >>Dual and opposing roles of presynaptic Ca2+ influx for spontaneous GABA release from rat medial preoptic nerve terminals
2002 (English)In: Journal of Physiology, ISSN 0022-3751, E-ISSN 1469-7793, Vol. 542, no 1, 131-146 p.Article in journal (Refereed) Published
Identifiers
urn:nbn:se:umu:diva-25913 (URN)10.1113/jphysiol.2001.015610 (DOI)
Available from: 2009-09-10 Created: 2009-09-10 Last updated: 2017-12-13Bibliographically approved
4. Differential control of spontaneous and evoked GABA release by presynaptic L-type Ca2+ channels in the rat medial preoptic nucleus
Open this publication in new window or tab >>Differential control of spontaneous and evoked GABA release by presynaptic L-type Ca2+ channels in the rat medial preoptic nucleus
(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
L-type Ca2+ channel, GABA release, synaptic plasticity, post-tetanic potentiation, medial preoptic nucleus
National Category
Physiology
Research subject
Physiology
Identifiers
urn:nbn:se:umu:diva-25870 (URN)
Available from: 2009-09-08 Created: 2009-09-08 Last updated: 2011-04-07Bibliographically approved

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