Differential connectivity of short- vs. long-range extrinsic and intrinsic cortical inputs to perirhinal neurons.

The perirhinal cortex plays a critical role in recognition and associative memory. However, the network properties that support perirhinal contributions to memory are unclear. To shed light on this question, we compared the synaptic articulation of short- and long-range inputs from the perirhinal cortex or temporal neocortex with perirhinal neurons in rats. Iontophoretic injections of the anterograde tracer Phaseolus vulgaris-leucoagglutinin (PHAL) were performed at different rostrocaudal levels of the ventral temporal neocortex or perirhinal cortex, and electron microscopic observations of anterogradely labeled (PHAL(+)) axon terminals found at perirhinal sites adjacent to or rostrocaudally distant from the injection sites were performed. After neocortical injections, the density of PHAL(+) axons in the perirhinal cortex decreased steeply with rostrocaudal distance from the injection sites, much more so than following perirhinal injections. Otherwise, similar results were obtained with neocortical and perirhinal injections. In both cases, most (76-86%) PHAL(+) axon terminals formed asymmetric synapses, typically with spines (type A, 83-89%) and less frequently with dendritic profiles (type B, 11-17%). The remaining terminals formed symmetric synapses with dendritic profiles (type C, 14-23%). Type B and C synapses were 2.4-2.6 times more frequent in short- than long-range connections. The postsynaptic elements in type A-C synapses were identified with immunocytochemistry for CAMKIIα, a marker of glutamatergic cortical neurons. Type A and C terminals contacted CAMKIIα-positive principal cells, whereas type B synapses contacted presumed inhibitory neurons. Overall, these results suggest that principal perirhinal neurons are subjected to significantly more inhibition from short- than from long-range cortical inputs, an organization that likely impacts perirhinal contributions to memory.