Emergence of epilepsy in a transgenic mouse strain that over-expressesbrain- derived neurotrophic factor in theforebrain

Structural changes that alter hippocampal functional
circuitry are implicated in learning impairments, mood
disorders and epilepsy. Failure to properly gate neuronal
activity arriving in hippocampus may be critical
in developing synaptic circuits that generate seizures
due to sustained elevations in hippocampal BDNF.
Our data shows higher number of synaptic contact
points (spines) on dendritic surfaces of granule cells
in 2-3 month-old TgBDNF mice compared to WT
mice, suggesting that there is increased cortical input
onto granule cells. The dysregulation in mature GC
circuitry in seizure dormant period in TgBDNF mice indicates
early seizure susceptibility. Both mature GCs
and immature GCs will show structural alterations in
their input and/or output regions in TgBDNF mice long
before full motor seizures are detectable pinpointing
early dysregulations in the gating properties of these
input neurons to hippocampus, favoring enhanced information
processing and propagation. These collective
results will help pinpoint intervention targets for
seizure prevention.