Abstracts

Rationale: Neurogenesis occurs in adult human brains and adult human neuronal progenitors (AHNPs) have been isolated from surgical specimens. AHNPs can be cultured and expanded in vitro and they can differentiate into cells that are morphologically similar to neurons. An important unanswered question is whether transplanted AHNP-derived neurons are functional and able to integrate into host networks. The present study aimed to answer this question. Methods: AHNPs were obtained from hippocampal specimens from a 13 year-old female with temporal lobe epilepsy. AHNPs were transduced with rhGFP-lenti viral vectors. They were transplanted into the neocortex of rat pups on postnatal day 1. Whole cell recordings were performed in cortical slices from the rats 17-21 days after transplantation. AHNP-derived neurons were identified using fluorescence microscopy. The firing properties, spontaneous excitatory and inhibitory postsynaptic currents (sEPSCs and sIPSCs) of AHNP-derived (human) pyramidal neurons in layer V were recorded and compared to host (rat) layer V pyramidal neurons. Results: AHNP-derived neurons in layer V demonstrated regular firing patterns during depolarizing currents and the frequency of firing was not significantly different from host pyramidal cells. The frequencies were 23.67 0.78 Hz for AHNP-derived neurons (n = 12) and 23.33 0.86 Hz for host neurons (n = 10, P > 0.1). Frequency and amplitude of sEPSCs from AHNP-derived and host layer V pyramidal neurons were quantified and compared. There were no differences between the two types of neuron (Table 1). Frequency and amplitude of sIPSCs were also compared and there were no differences between AHNP-derived and host neurons (Table 1). Conclusions: AHNP-derived neurons in neocortex of rat brain have firing properties similar to host neurons. They receive excitatory and inhibitory synapses from other neurons. The synaptic activities in AHNP-derived neurons are not different from neighboring host neurons. Our results suggest that AHNPs are able to generate functional neurons which integrate into host neuronal networks. This provides promising data on the potential for AHNPs to serve as therapeutic agents in diseases with altered neuronal circuitry such as epilepsy.