The expression pattern of somatostatin and calretinin by postnatal hippocampal interneurons is regulated by activity-dependent and -independent determinants.

Hippocampal interneurons form distinct populations identified on the basis of their projection pattern and neurochemical characteristics, which includes the expression of specific neuropeptides and/or calcium-binding proteins. The neurochemical maturation of hippocampal interneurons is largely a postnatal event, and factors which govern this maturation are presently unknown. Using slice cultures, we have investigated the role of neuronal activity in regulating the expression of somatostatin and calretinin during the postnatal maturation of hippocampal interneurons. Blocking inhibitory activity with bicuculline, or excitatory activity with 6,7-dinitroquinoxaline-2,3-dione, for 14 days in slice cultures from seven-day-old rat increased and decreased, respectively, the number of somatostatin-immunoreactive neurons. Withdrawal of the blocking agents resulted in a reversal of the effects on somatostatin immunoreactivity. In addition, bicuculline slightly increased the number of calretinin-positive neurons, while 6,7-dinitroquinoxaline-2,3-dione exerted no effect. However, bicuculline and 6,7-dinitroquinoxaline-2,3-dione markedly increased and decreased, respectively, the number of calretinin-labelled axons. Despite activity-linked modifications of immunoreactivity levels, no change in the organotypic location of somatostatin-labelled neurons was observed, whatever the treatment. Double labelling studies demonstrated that somatostatin and calretinin were expressed by different neurons, even when the number of labelled cells was highly increased. These results show that the levels of expression of somatostatin and calretinin in maturing hippocampal interneurons are tuned to the endogenous balance of excitatory and inhibitory activity. In contrast, the neurochemical specificity of each subtype of interneurons does not depend upon variations in neuronal activity.