In the primate neocortex, little is known about the possible associations between functional subclasses of GABA neurons, their morphological properties and calcium-binding protein (CaBP) content. We used whole-cell current clamp recordings, combined with intracellular labeling and fluorescence immunohistochemistry, to determine these relationships for interneurons in layers 2–3 of monkey prefrontal cortex (PFC). Eighty-one interneurons were included in the analysis. Thirty-eight of these cells showed immunoreactivity for one of the three CaBPs tested. Co-localization of more than one CaBP was not observed in any of the interneurons examined. Interneurons with different CaBPs formed distinct populations with specific physiological membrane properties and morphological features. Parvalbumin (PV)-positive cells had the physiological properties characteristic of fast-spiking interneurons (FS) and the morphology of basket or chandelier neurons. Most calretinin (CR)-containing cells had the physiological properties ascribed to non-fast-spiking cells (non-FS) and a vertically oriented axonal morphology, similar to that of double bouquet cells. Calbindin (CB)-positive interneurons also had non-FS properties and included cells with double bouquet morphology or with a characteristic dense web of axonal collaterals in layer 1. Classification of the interneurons based on cluster analysis of multiple electrophysiological properties suggested the existence of at least two distinct groups of interneurons. The first group contained mainly PV-positive FS cells and the second group consisted predominantly of CR- and CB-positive non-FS interneurons. These findings may help to illuminate the functional roles of different groups of interneurons in primate PFC circuitry.

In the prefrontal cortex (PFC) during working memory tasks fast-spiking (FS) interneurons might shape the spatial selectivity of pyramidal cell firing. In order to provide time control of pyramidal cell activity, incoming excitatory inputs should excite FS interneurons more vigorously than pyramidal cells. This can be achieved if subthreshold excitatory responses of interneurons are considerably stronger and faster than those in pyramidal neurons. Here we compared the functional properties of excitatory post-synaptic potentials (EPSPs) between pyramidal cells and FS interneurons in slices from monkey dorsolateral PFC and rat prelimbic cortex. Miniature, unitary (in connected pairs or by minimal stimulation) and compound (evoked by electrical stimulation of the white matter) EPSPs were recorded in whole cell mode. We found that EPSPs were significantly larger and faster in FS interneurons than those recorded from pyramidal cells, consistent with the idea of more efficient recruitment of FS interneurons compared to pyramidal neurons. Similar results were obtained in monkey and rat PFC, suggesting a stable role of FS interneurons in this circuitry across species.

In primates, little is known about intrinsic electrophysiological properties of neocortical neurons and their morphological correlates. To classify inhibitory cells (interneurons) in layers 2–3 of monkey dorsolateral prefrontal cortex we used whole cell voltage recordings and intracellular labeling in slice preparation with subsequent morphological reconstructions. Regular spiking pyramidal cells have been also included in the sample. Neurons were successfully segregated into three physiological clusters: regular-, intermediate-, and fast-spiking cells using cluster analysis as a multivariate exploratory technique. When morphological types of neurons were mapped on the physiological clusters, the cluster of regular spiking cells contained all pyramidal cells, whereas the intermediate- and fast-spiking clusters consisted exclusively of interneurons. The cluster of fast-spiking cells contained all of the chandelier cells and the majority of local, medium, and wide arbor (basket) interneurons. The cluster of intermediate spiking cells predominantly consisted of cells with the morphology of neurogliaform or vertically oriented (double-bouquet) interneurons. Thus a quantitative approach enabled us to demonstrate that intrinsic electrophysiological properties of neurons in the monkey prefrontal cortex define distinct cell types, which also display distinct morphologies.

The heterogeneity of γ-aminobutyric acid interneurons in the rodent neocortex is well-established, but their classification into distinct subtypes remains a matter of debate. The classification of interneurons in the primate neocortex is further complicated by a less extensive database of the features of these neurons and by reported interspecies differences. Consequently, in this study we characterized 8 different morphological types of interneurons from monkey prefrontal cortex, 4 of which have not been previously classified. These interneuron types differed in their expression of molecular markers and clustered into 3 different electrophysiological classes. The first class consisted of fast-spiking parvalbumin-positive chandelier and linear arbor cells. The second class comprised 5 different morphological types of continuous-adapting calretinin- or calbindin-positive interneurons that had the lowest level of firing threshold. However, 2 of these morphological types had short spike duration, which is not typical for rodent adapting cells. Neurogliaform cells (NGFCs), which coexpressed calbindin and neuropeptide Y, formed the third class, characterized by strong initial adaptation. They did not exhibit the delayed spikes seen in rodent NGFCs. These results indicate that primate interneurons have some specific properties; consequently, direct translation of classification schemes developed from studies in rodents to primates might be inappropriate.

Differences in the developmental origin and relative proportions of biochemically distinct classes of cortical neurons have been found between rodents and primates. In addition, species differences in the properties of certain cell types, such as neurogliaform cells, have also been reported. Consequently, in this study we compared the anatomical and physiological properties of parvalbumin (PV)-positive basket interneurons in the prefrontal cortex of macaque monkeys and rats. The somal size, total dendritic length, and horizontal and vertical spans of the axonal arbor were similar in monkeys and rats. Physiologically, PV basket cells could be identified as fast-spiking interneurons in both species, based on their short spike and high-frequency firing without adaptation. However, important interspecies differences in the intrinsic physiological properties were found. In monkeys, basket cells had a higher input resistance and a lower firing threshold, and they generated more spikes at near-threshold current intensities than those in rats. Thus monkey basket cells appeared to be more excitable. In addition, rat basket cells consistently fired the first spike with a substantial delay and generated spike trains interrupted by quiescent periods more often than monkey basket cells. The frequency of miniature excitatory postsynaptic potentials in basket cells was considerably higher in rats than that in monkeys. These differences between rats and monkeys in the electrophysiological properties of PV-positive basket cells may contribute to the differential patterns of neuronal activation observed in rats and monkeys performing working-memory tasks.

The Cav2.1 (P/Q-) and Cav2.2 (N-type) voltage-gated calcium channels (VGCCs) play a predominant role in neurotransmitter release at central synapses, but their distribution is not uniform across different types of synapses. Although the functional significance of the differential distribution of N- and P/Q-type VGCCs is poorly understood, distinct types of VGCCs appear to differentially affect synaptic properties. For example, P/Q-type VGCCs are located closer to release sites and are less affected by G-protein-mediated inhibition than are N-type VGCCs. Thus P/Q-type VGCCs might be beneficial at synapses with high probability of release and precise timing of neurotransmission, such as the inhibitory inputs from parvalbumin-containing fast-spiking (FS) interneurons to pyramidal cells (PCs) in the neocortex. To determine whether VGCCs types predominate at synapses from FS interneurons to PCs in rat prefrontal cortex, whole cell paired recordings (n = 14) combined with intracellular labeling and fluorescence immunohistochemistry for parvalbumin were performed in acute slices. Bath application of the specific N-type VGCC blocker ω-conotoxin-GVIa (1 μM) did not alter inhibitory postsynaptic potential amplitude, failure rate, or synaptic dynamics; in contrast, application of P/Q-type VGCC blocker ω-agatoxin-IVa (0.5 μM) completely and irreversibly blocked neurotransmission. These results indicate that P/Q-type VGCCs mediate the GABA release from parvalbumin-positive FS interneurons to PCs in the rat neocortex.