title: Synaptic targets of calretinin-containing axon terminals in macaque monkey prefrontal cortex.
abstract: The coordinated activity of specific populations of pyramidal cells and GABA-containing, local circuit neurons in the primate prefrontal cortex (PFC) appears to be critical for working memory. Different subclasses of GABA-containing neurons can be distinguished by their content of the calcium-binding proteins parvalbumin (PV) and calretinin (CR). The postsynaptic targets of PV-containing cells have been well characterized in the primate PFC, but the postsynaptic targets of CR-containing neurons in this cortical region remain unknown. In the present study, we used immuno-electron microscopy to examine the synaptic type and postsynaptic targets of CR-immunoreactive (IR) axon terminals in the superficial and deep layers of macaque monkey PFC. Labeled axon terminals formed both symmetric and asymmetric synapses. Within the superficial layers, 93% of the synapses formed by CR-IR were symmetric, whereas in the deep layers the labeled axon terminals forming synapses were more evenly divided between symmetric (57%) and asymmetric (43%). The primary postsynaptic target of these two populations of CR-IR axon terminals also differed; unlabeled dendritic shafts were the predominant target of the symmetric synapses, whereas dendritic spines were the most common target of the asymmetric synapses. In addition, the mean cross-sectional area of the terminals forming asymmetric synapses was significantly larger than that of the terminals forming symmetric synapses. The presence of CR-IR asymmetric synapses suggested that they might arise from neurons that do not utilize GABA; indeed, dual-label fluorescent immunocytochemistry revealed that a subpopulation (23%) of CR-containing neurons in monkey PFC were not GABA-IR. These findings indicate that the synaptology of CR-containing neurons is more heterogeneous than that of PV-containing cells and suggests that the contributions of CR-containing neurons to cognitive processes mediated by the PFC may be more diverse.
authors.affiliation: Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA 15213, USA.
authors.forename: D S
authors.initials: DS
authors.lastname: Melchitzky
authors.forename: S M
authors.initials: SM
authors.lastname: Eggan
authors.forename: D A
authors.initials: DA
authors.lastname: Lewis
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism* / Q000648:ultrastructure; D064032:Calbindin 2; D002452:Cell Count / Q000379:methods; D007150:Immunohistochemistry / Q000379:methods; D008252:Macaca fascicularis; D008297:Male; D016253:Microscopy, Immunoelectron / Q000379:methods; D016571:Neural Networks, Computer; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D010320:Parvalbumins / Q000378:metabolism; D017397:Prefrontal Cortex / Q000166:cytology*; D064030:S100 Calcium Binding Protein G / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism* / Q000648:ultrastructure; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D064032:Calbindin 2; D010320:Parvalbumins; D064030:S100 Calcium Binding Protein G; D005680:gamma-Aminobutyric Acid