Astrocytes are important for sprouting in the septohippocampal circuit

Damage to the fimbria-fornix, and separately to the perforant path, leads to distinct and dramatic time-dependent increases in glial fibrillary acidic protein immunoreactivity (GFAP-IR) in specific areas of the hippocampal formation. Specifically, fimbria-fornix lesions resulted in an increase in the GFAP-IR in the pyramidal and oriens area of the CA3 as well as the inner molecular layer of the dentate gyrus. In addition, in the septum ipsilateral to the lesion, there was a rapid and robust increase in GFAP-IR in the dorsal lateral quadrant of the septum, but not in the medial region. Only after 30 days did the GFAP-IR reach the medial septum. Following perforant path lesions, there was a selective increase in GFAP-IR in the outer molecular layer of the dentate gyrus. Most of these changes were transient and had disappeared by 30 days postlesion. We speculate that the increase in GFAP-IR in these target areas is a necessary requirement for the sprouting responses that are observed. This hypothesis is supported by the fact that astrocytes secrete NGF in vitro and that NGF activity increases in these target areas following these same lesions. A mechanism for the selective activation of the astrocytes through the initial activation of microglia and secretion of interleukin-1 is postulated.