Pathway-Specific Utilization of Synaptic Zinc in the Macaque Ventral Visual Cortical Areas

Synaptic zinc is an activity-related neuromodulator, enriched in hippocampal mossy fibers and a subset of glutamatergic cortical projections, exclusive of thalamocortical or corticothalamic. Some degree of pathway specificity in the utilization of synaptic zinc has been reported in rodents. Here, we use focal injections of the retrograde tracer sodium selenite to identify zinc-positive (Zn+) projection neurons in the monkey ventral visual pathway. After injections in V1, V4, and TEO areas, neurons were detected preferentially in several feedback pathways but, unusually, were restricted to deeper layers without involvement of layers 2 or 3. Temporal injections resulted in more extensive labeling of both feedback and intratemporal association pathways. The Zn+ neurons had a broader laminar distribution, similar to results from standard retrograde tracers. After anterograde tracer injection in area posterior TE, electron microscopic analysis substantiated that a proportion of feedback synapses was colabeled with zinc. Nearby injections, Zn+ intrinsic neurons concentrated in layer 2, but in temporal areas were also abundant in layer 6. These results indicate considerable pathway and laminar specificity as to which cortical neurons use synaptic zinc. Given the hypothesized roles of synaptic zinc, this is likely to result in distinct synaptic properties, possibly including differential synaptic plasticity within or across projections.