Synaptic zinc is co-released with glutamate from a subpopulation of glutamatergic terminals in the neocortex and modulates neurotransmission. Using histochemical detection we showed that the level of synaptic zinc was regulated by sensory experience in the barrel cortex of mice and this suggested involvement of synaptic zinc in cortical plasticity. We sought to establish a new experimental approach to directly investigate the role of synaptic zinc in neuronal plasticity by its local removal (chelation) in vivo in the barrel cortex. The aim of present study was also to investigate whether long-lasting chelation has any effect on mapping of functional changes by 2-deoxyglucose (2DG) uptake. We used highly specifi c zinc chelator, tetrakis- (2-pyridylmethyl)-ethylenediamine (TPEN; 5 mM). We examined different implants stereotaxically placed directly on the barrel cortex or on the dura. No suffi cient chelation was observed when Elvax polimer was used to release TPEN. Implantation of spongostan saturated with TPEN solution resulted in a complete loss of zinc staining in the entire cortical depth under the implant for more than 24 h but not more than 48 h. After unilateral spongostan implantation, TPEN was added daily during 3 days to maintain the continuous chelation. Then, the 2DG study was performed with two-sided sensory stimulation of selected vibrissae. The 2DG uptake within cortical representation of stimulated vibrissae was increased under the implant in comparison to control side. However the width of labeled region remained unchanged in all cortical layers, and therefore this method is useful to study the role of zinc in the cortex. Supported by the Scientifi c Network of Ministry of Science and Higher Education, and by statutory funds for the Nencki Institute.