Role of Endogenous BDNF and NT3 for Synaptic Transmission and Plasticity in the Dentate gyrus

Sammanfattning: 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.