Abstracts

The neurotrophin, brain derived neurotrophic factor (BDNF), plays a critical role in neural development, migration, plasticity, recovery from injury and learning. In epileptogenic brain areas, such as the temporal lobe, BDNF is up-regulated during repeated seizures, whereby it is proposed to enhance glutamatergic synaptic transmission and decrease GABAergic inhibition, enhancing the overall excitability of the network (Neuroscientist. 2005 11(4):282-7). BDNF additionally enhances intrinsic neuronal membrane excitability (Nature 1999;401 (6756):918-21). Thus, BDNF has been proposed to promote epileptiform activity (Trends Neurosci. 2001; 24(1):47-53). Although, BDNF over-expression and exogenous application lead to reduced seizure threshold in experimental models where inhibition is reduced, no one has before shown that BDNF alone induces cortical epileptiform activity. Here, we test the hypothesis that BDNF application can trigger epileptiform activity., We used brain slice preparations containing temporal lobe cortex of CD-1 mice (age P10-P15), where we simultaneously recorded network population activity and from individual cortical neurons using whole cell current clamp techniques., BDNF application (50ng/mL) triggered paroxysmal depolarization shift (PDS) bursting (n=9/10); PDS bursts were NMDA-dependent and blocked by the NMDA antagonist, CPP. BDNF enhanced bursting properties in intrinsic bursting (IB) neurons (n=3), but not in non-rhythmogenic neurons (n=7). Application of BDNF also induced seizure-like population activity in some (n=8) preparations., Our data support our working hypothesis that BDNF can preferentially enhance bursting properties of rhythmogenic neurons that may trigger SLA. Additionally, BDNF can trigger PDS bursting, one of the hallmarks of epilepsy. Thus, our results suggest that BDNF signaling may be involved in the genesis of epilepsy., (Supported by NIH RO1 HL079294-02 (AKT).)