Regulation of astrocytic structure by neuronal activity

Numerous accounts of structural changes in glial cells in regions of neuronal injury and degeneration describe an increase in astrocytic immunoreactivity for glial fibrillary acidic protein (GFAP) and an increase in astrocytic process length and number. Increased GFAP immunoreactivity (GFAP-IR) first appears 1-10 days following such lesions. The recent report of an increase in GFAP-IR and silver-impregnated glial processes within hours of deafferentation of the chick cochlear nucleus suggests that the signal initiating the glial changes in the cessation of neuronal action potentials rather than signals specific to neuronal degeneration.; The objective of the present work was to determine whether neuronal electrical activity does indeed regulate astrocytic structure in the cochlear nucleus. This was tested by: (1) unilaterally blocking 8th nerve action potentials with tetrodotoxin, and (2) by unilaterally stimulating the 8th nerve in a brain stem slice preparation. Differences in GFAP-IR between the active and inactive cochlear nuclei within individual tissue sections were measured. Both manipulations produced an increase in GFAP-IR on the unstimulated side of the brain. This regulation of astrocytic processes by neuronal activity also returns GFAP-IR to control level when activity is restored. A similar reaction to afferent activity blockade occurs in adult chickens and in gerbils, indicating that the reaction is not unique to young animals or to birds. Double-labeling GFAP and protein synthesis revealed no anatomical relationship between the reactive astrocytic process and neurons destined to die following afferent activity blockade.; The mechanisms by which neuronal activity regulates astrocytic structure were explored using the slice preparation and cell cultures. Stimulation studies using slices indicate that either pre- or postsynaptic neuronal activation is sufficient, ruling out a requirement for synaptic transmission or calcium-dependent release of glioactive substance. This work and studies of cultured astrocytes suggest that extracellular potassium, released by active neurons, may be the signal by which auditory nerve action potentials regulate astrocytic structure in the chick cochlear nucleus.