In the cerebral cortex, local circuit neurons provide critical inhibitory control over the activity of pyramidal neurons, the major class of excitatory efferent cortical cells. The calcium-binding proteins, calretinin, calbindin, and parvalbumin, are expressed in a variety of cortical local circuit neurons. However, in the primate prefrontal cortex, relatively little is known, especially with regard to calretinin, about the specific classes or distribution of local circuit neurons that contain these calcium-binding proteins. In this study, we used immunohistochemical techniques to characterize and compare the morphological features and distribution in macaque monkey prefrontal cortex of local circuit neurons that contain each of these calcium-binding proteins. On the basis of the axonal features of the labeled neurons, and correlations with previous Golgi studies, calretinin appeared to be present in double-bouquet neurons, calbindin in neurogliaform neurons and Martinotti cells, and parvalbumin in chandelier and wide arbor (basket) neurons. Calretinin was also found in other cell populations, such as a distinctive group of large neurons in the infragranular layers, but it was not possible to assign these neurons to a known cell class. In addition, although the animals studied were adults, immunoreactivity for both calretinin and calbindin was found in Cajal-Retzius neurons of layer I. Dual labeling studies confirmed that with the exception of the Cajal-Retzius neurons, each calcium-binding protein was expressed in separate populations of prefrontal cortical neurons. Comparisons of the laminar distributions of the labeled neurons also indicated that these calcium-binding proteins were segregated into discrete neuronal populations. Calretinin-positive neurons were present in greatest density in deep layer I and layer II, calbindin-immunoreactive cells were most dense in layers II-superficial III, and parvalbumin-containing neurons were present in greatest density in the middle cortical layers. In addition, the relative density of calretinin-labeled neurons was approximately twice that of the calbindin- and parvalbumin-positive neurons. However, within each group of labeled neurons, their laminar distribution and relative density did not differ substantially across regions of the prefrontal cortex. These findings demonstrate that calretinin, calbindin, and parvalbumin are markers of separate populations of local circuit neurons in monkey prefrontal cortex, and that they may be useful tools in unraveling the intrinsic inhibitory circuitry of the primate prefrontal cortex in but normal and disease states.

Metabotropic glutamate receptor 1 (mGluR1) is a member of a large family of G-protein-coupled glutamate receptors, the physiological functions of which are largely unknown. Mice deficient in mGluR1 have severe motor coordination and spatial learning deficits. They have no gross anatomical or basic electrophysiological abnormalities in either the cerebellum or hippocampus, but they show impaired cerebellar long-term depression and hippocampal mossy fibre long-term potentiation. mGluR1-deficient mice should therefore be valuable models for studying synaptic plasticity.

In order to compare the frontal cortex of rat and macaque monkey, cortical and subcortical afferents to subdivisions of the medial frontal cortex (MFC) in the rat were analyzed with fluorescent retrograde tracers. In addition to afferent inputs common to the whole MFC, each subdivision of the MFC has a specific pattern of afferent connections. The dorsally situated precentral medial area (PrCm) was the only area to receive inputs from the somatosensory cortex. The specific pattern of afferents common to the ventrally situated prelimbic (PL) and infralimbic (IL) areas included projections from the agranular insular cortex, the entorhinal and piriform cortices, the CA1-CA2 fields of the hippocampus, the subiculum, the endopiriform nucleus, the amygdalopiriform transition, the amygdalohippocampal area, the lateral tegmentum, and the parabrachial nucleus. In all these structures, the number of retrogradely labeled cells was larger when the injection site was located in area IL. The dorsal part of the anterior cingulate area (ACd) seemed to be connectionally intermediate between the adjacent areas PrCm and PL; it receives neither the somatosensory inputs characteristic of area PrCm nor the afferents characteristic of areas PL and IL, with the exception of the afferents from the caudal part of the retrosplenial cortex. A comparison of the pattern of afferent and efferent connections of the rat MFC with the pattern of macaque prefrontal cortex suggests that PrCm and ACd areas share some properties with the macaque premotor cortex, whereas PL and IL areas may have characteristics in common with the cingulate or with medial areas 24, 25, and 32 and with orbital areas 12, 13, and 14 of macaques.