Effects of enriched housing on the neuronal morphology of mice that lack zinc transporter 3 (ZnT3) and vesicular zinc

ABSTRACTIn the central nervous system, certain neurons store zinc within the synaptic vesicles of their axon terminals. This vesicular zinc can then be released in an activity-dependent fashion as an intercellular signal. The functions of vesicular zinc are not entirely understood, but evidence suggests that it is important for some forms of experience-dependent plasticity in the brain. The ability of neurons to store and release vesicular zinc is dependent on expression of the vesicular zinc transporter, ZnT3. Here, we examined the neuronal morphology of mice that lack ZnT3. Brains were collected from mice housed under standard laboratory conditions and from mice housed in enriched environments – large, multilevel enclosures with running wheels, numerous objects and tunnels, and a greater number of cage mates. Golgi-Cox staining was used to visualize neurons for analysis of dendritic length and dendritic spine density. Neurons were analyzed from the barrel cortex, striatum, basolateral amygdala, and hippocampus (CA1). ZnT3 knockout mice, relative to wild type mice, exhibited increased basal dendritic length in the layer 2/3 pyramidal neurons of barrel cortex, independently of housing condition. Environmental enrichment decreased apical dendritic length in these same neurons and increased dendritic spine density on striatal medium spiny neurons. Elimination of ZnT3 did not modulate any of the effects of enrichment. Our results provide no evidence that vesicular zinc is required for the experience-dependent changes that occur in response to environmental enrichment. They are consistent, however, with recent reports suggesting increased cortical volume in ZnT3 knockout mice.