Role of Endogenous BDNF and NT3 for Synaptic Transmission and Plasticity in the Dentate gyrus
(2002)- Abstract
- The neurotrophins, notably brain-derived neurotrophic factor (BDNF) and neurotrophin 3 (NT3), modulate synaptic transmission and synaptic plasticity in the adult mammalian brain. Recent data suggest that neurotrophins might be mediators of activity-dependent synaptic plasticity. Such plasticity is believed to be a cellular correlate for important processes like learning, but also for diseases, for instance epilepsy. Indeed, reduced levels of endogenous BDNF or NT3 seem to be protective against the development of epilepsy in animal models of the disorder. The aim of this thesis was to study the effect of endogenous BDNF and NT3 on synaptic transmission in an area of the brain that has been proposed to be involved in the development of... (More)
- The neurotrophins, notably brain-derived neurotrophic factor (BDNF) and neurotrophin 3 (NT3), modulate synaptic transmission and synaptic plasticity in the adult mammalian brain. Recent data suggest that neurotrophins might be mediators of activity-dependent synaptic plasticity. Such plasticity is believed to be a cellular correlate for important processes like learning, but also for diseases, for instance epilepsy. Indeed, reduced levels of endogenous BDNF or NT3 seem to be protective against the development of epilepsy in animal models of the disorder. The aim of this thesis was to study the effect of endogenous BDNF and NT3 on synaptic transmission in an area of the brain that has been proposed to be involved in the development of epilepsy, the dentate gyrus in the hippocampal formation. We did this by using electrophysiological techniques to measure synaptic activity in brain slices from transgenic mice with lowered endogenous levels of BDNF or NT3, by applying BDNF scavenging agents or recombinant BDNF or NT3. Both BDNF and NT3 influenced short-term plasticity of excitatory synaptic transmission onto granule cells in the dentate gyrus. The effects of BDNF and NT3 were input specific. Thus, NT3 modulated synaptic transmission only in synapses between lateral perforant path and granule cells, whereas BDNF affected medial perforant path to granule cell synapses exclusively. Inhibitory synaptic transmission was altered in BDNF but not NT3 deficient mice. The former displayed an increased frequency of action potential independent spontaneous events, and also altered short-term plasticity of evoked inhibitory synaptic transmission. In animals induced to have an experimental form of epilepsy (kindled animals) no differences were observed in inhibitory synaptic transmission between BDNF deficient and wild-type mice. In conclusion, this thesis work shows specific influences of BDNF and NT3 on excitatory and inhibitory synaptic transmission and on short-lasting synaptic plasticity in the dentate gyrus. This would arguably have consequences on the excitability of this system, and could affect the gating properties of the dentate gyrus during epileptogenesis. (Less)
- Abstract (Swedish)
- Popular Abstract in Swedish
Tillväxtfaktorer påverkar signaler mellan celler i hjärnan Människors hjärnor innehåller flera miljarder hjärnceller, vilka är förutsättningen för vårt beteende, våra känslor och våra tankar. Hjärncellerna bildar kontakter, synapser, med varandra. Genom dessa överförs signaler från en cell till en annan. Varje cell kontaktar en mängd andra celler, både sådana med liknande funktion och sådana som har helt andra uppgifter. Beroende på vilken grupp av celler som är aktiv händer olika saker: vi kan till exempel utföra en rörelse eller känna oss glada eller minnas doften av nybakat bröd. När vi växer, utvecklas och lär oss nya saker, bildas nya kontakter mellan cellerna i hjärnan. Dessutom förändras... (More) - Popular Abstract in Swedish
Tillväxtfaktorer påverkar signaler mellan celler i hjärnan Människors hjärnor innehåller flera miljarder hjärnceller, vilka är förutsättningen för vårt beteende, våra känslor och våra tankar. Hjärncellerna bildar kontakter, synapser, med varandra. Genom dessa överförs signaler från en cell till en annan. Varje cell kontaktar en mängd andra celler, både sådana med liknande funktion och sådana som har helt andra uppgifter. Beroende på vilken grupp av celler som är aktiv händer olika saker: vi kan till exempel utföra en rörelse eller känna oss glada eller minnas doften av nybakat bröd. När vi växer, utvecklas och lär oss nya saker, bildas nya kontakter mellan cellerna i hjärnan. Dessutom förändras kontakterna beroende på våra erfarenheter, genom att tillgången på olika kemiska ämnen i kontakternas närhet påverkas av vad som händer i hjärnan. Kontakterna kan ändras så att signalen från en hjärncell till en annan blir starkare eller svagare, och detta är viktigt för att informationsflödet i hjärnan ska vara väl anpassat efter människors olika behov. Vi har undersökt om en grupp tillväxtfaktorer, neurotrofiner, som tidigare varit mest kända för att påverka nervers överlevnad och utveckling, kan påverka hur signalerna mellan hjärncellerna fungerar. För att göra detta har vi använt genetiskt förändrade möss, som i hjärnan har lägre koncentration av de här ämnena än normala möss. I övrigt är de båda mössen genetiskt identiska, så om man hittar en skillnad mellan dem är det sannolikt att det beror på skillnaden i neurotrofin-koncentration. De genetiskt ändrade mössen verkar må bra, de äter, lever och förökar sig precis som andra möss. Anledningen att vi ville studera detta är att de här speciella mössen inte utvecklar epilepsi lika lätt som vanliga möss. Epilepsi kan ju beskrivas som en sjukdom där signaleringen mellan hjärncellerna inte fungerar som den ska. I våra studier fann vi att neurotrofiner påverkar signaleringen mellan hjärnceller i ett område av hjärnan som man tror är viktigt för hur epilepsi utvecklas. Den här kunskapen kan bidra till att man bättre förstår dels hur hjärnceller i en frisk hjärna signalerar, dels vad som händer när en människa utvecklar epilepsi (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/464895
- author
- Olofsdotter, Klara LU
- supervisor
- opponent
-
- Professor Bramham, Clive, Physiology, Bergen university, Bergen, Norway
- organization
- publishing date
- 2002
- type
- Thesis
- publication status
- published
- subject
- keywords
- hippocampus, dentate gyrus, GABA, glutamate, synaptic transmission, synaptic plasticity, Brain-derived neurotrophic factor, neurotrophin 3, Neurologi, neurophysiology, neuropsychology, Neurology, electrophysiology, neurofysiologi, neuropsykologi
- pages
- 102 pages
- publisher
- Section for Restorative Neurology, BMC A11, SE-221 84 Lund, Sweden,
- defense location
- Fernstrom lecture hall
- defense date
- 2002-10-21 13:00:00
- ISBN
- 91-628-5349-X
- language
- English
- LU publication?
- yes
- additional info
- Article: I Merab Kokaia, Fredrik Asztely, Klara Olofsdotter, Carlos Balet-Sindreu, Dimitri Kullmann, Olle LindvallEndogenous neurotrophin-3 regulates short-term plasticity at lateral perforant path-granule cell synapses.Journal of Neuroscience 18(21): 8730-9. 1998 Article: II Fredrik Asztely, Merab Kokaia, Klara Olofsdotter, Unn Örtegren, Olle LindvallAfferent-specific modulation of short-term synaptic plasticity by neurotrophins in dentate gyrusEuropean Journal of Neuroscience 12(2): 662-9. 2000 Article: III Klara Olofsdotter, Olle Lindvall, Fredrik AsztelyIncreased synaptic inhibition in dentate gyrus of mice with reduced levels of endogenous brain-derived neurotrophic factor.Neuroscience 101(3): 531-9. 2000 Article: IV Klara Olofsdotter, Avtandil Nanobashvili, Olle Lindvall, Fredrik AsztelyInhibitory synaptic transmission and plasticity in kindled BDNF heterozygous mice.Manuscript in preparation
- id
- 3782cdff-68c8-4092-93b3-72143163d62b (old id 464895)
- date added to LUP
- 2016-04-04 09:52:49
- date last changed
- 2018-11-21 20:55:30
@phdthesis{3782cdff-68c8-4092-93b3-72143163d62b,
abstract = {{The neurotrophins, notably brain-derived neurotrophic factor (BDNF) and neurotrophin 3 (NT3), modulate synaptic transmission and synaptic plasticity in the adult mammalian brain. Recent data suggest that neurotrophins might be mediators of activity-dependent synaptic plasticity. Such plasticity is believed to be a cellular correlate for important processes like learning, but also for diseases, for instance epilepsy. Indeed, reduced levels of endogenous BDNF or NT3 seem to be protective against the development of epilepsy in animal models of the disorder. The aim of this thesis was to study the effect of endogenous BDNF and NT3 on synaptic transmission in an area of the brain that has been proposed to be involved in the development of epilepsy, the dentate gyrus in the hippocampal formation. We did this by using electrophysiological techniques to measure synaptic activity in brain slices from transgenic mice with lowered endogenous levels of BDNF or NT3, by applying BDNF scavenging agents or recombinant BDNF or NT3. Both BDNF and NT3 influenced short-term plasticity of excitatory synaptic transmission onto granule cells in the dentate gyrus. The effects of BDNF and NT3 were input specific. Thus, NT3 modulated synaptic transmission only in synapses between lateral perforant path and granule cells, whereas BDNF affected medial perforant path to granule cell synapses exclusively. Inhibitory synaptic transmission was altered in BDNF but not NT3 deficient mice. The former displayed an increased frequency of action potential independent spontaneous events, and also altered short-term plasticity of evoked inhibitory synaptic transmission. In animals induced to have an experimental form of epilepsy (kindled animals) no differences were observed in inhibitory synaptic transmission between BDNF deficient and wild-type mice. In conclusion, this thesis work shows specific influences of BDNF and NT3 on excitatory and inhibitory synaptic transmission and on short-lasting synaptic plasticity in the dentate gyrus. This would arguably have consequences on the excitability of this system, and could affect the gating properties of the dentate gyrus during epileptogenesis.}},
author = {{Olofsdotter, Klara}},
isbn = {{91-628-5349-X}},
keywords = {{hippocampus; dentate gyrus; GABA; glutamate; synaptic transmission; synaptic plasticity; Brain-derived neurotrophic factor; neurotrophin 3; Neurologi; neurophysiology; neuropsychology; Neurology; electrophysiology; neurofysiologi; neuropsykologi}},
language = {{eng}},
publisher = {{Section for Restorative Neurology, BMC A11, SE-221 84 Lund, Sweden,}},
school = {{Lund University}},
title = {{Role of Endogenous BDNF and NT3 for Synaptic Transmission and Plasticity in the Dentate gyrus}},
year = {{2002}},
}