Neocortical and hippocampal GABA-containing interneurons are susceptible to activity-dependent modulation, such as regulation of soma size, numbers of synaptic contacts, and levels of GABA or neuropeptide expression. In vitro, the effects of neuronal activity on morphology and gene expression of GABA-containing neurons are mimicked, in part, by members of the neurotrophin gene family, such as brain-derived neurotrophic factor (BDNF). In the neocortex and hippocampus, BDNF is synthesized and secreted in an activity-dependent manner by pyramidal neurons, the target cells of GABA-containing neurons, suggesting that BDNF is an activity-dependent, target-derived trophic factor for these interneurons. In support of this, neuronal activity fails to upregulate the expression of neuropeptide Y in hippocampal cultures from BDNF-deficient mice. We, therefore, hypothesize that neurotrophins might mediate some of the actions of neuronal activity on GABA-containing neurons.