BIOMEDICAL ENGINEERING

In-vitro preparations have been of great value to understand the the generation and propagation of both normal and abnormal neural activity in the brain. In the hippocampal slice preparation for example, the transverse hippocampal organization is maintained but the longitudinal synaptic processes that interconnect the CA3 region are severed. Yet longitunal processes such as the recurrent CA3 excitatory pathway are known to play an important role in epileptiform hyperexcitability. We have tested the hypothesis that the longitudinal pathway plays a crucial role in the generation and propagation of epileptiform activity generated by 4_aminopyridine (4-AP). We used a preparation that preserves both transverse and longitudinal pathways with an unfolded hippocampus preparation of young (P10-P24) mice using normal and 4-AP solutions. In 50µM 4-AP, antidromic activation of CA3 neurons induced the usual evoked potentials but also induced a self-regenerating wave of activity propagati ng along the CA3 region at a speed of 0.09m/s (3-5 times slower than axonal velocity). This longitudinal wave was also generated spontaneously traveling from the lateral to the septal region of the hippocampus. Glutamate synaptic blockers and transection of the pathway suppressed this wave suggesting that it is generated by a combination of synaptic transmission and axonal propagation. The self-regenerating wave first travels longitudinally along the CA3 pathway invading the CA1 region. This new self-regenerating wave in the hippocampus could be important to explain the role on the recurrent excitation pathway in the propagation and generation of seizures. Financial support was provided by the department of education for a GAANN fellowship in neural engineering and by National Institutes of Health.