Research reportNitric oxide synthase interneurons in the monkey cerebral cortex are subsets of the somatostatin, neuropeptide Y, and calbindin cells
Introduction
The neurons with the most obvious nNOS-immunoreactivity in the cerebral cortex are those which also contain intense immunoreactivity for the neuropeptides somatostatin and neuropeptide Y (NPY) [25], [26]. In the rat cerebral cortex many somatostatin-immunoreactive interneurons are Martinotti and wide arbor cells which have characteristic physiological responses [15], [16]. Axons immunoreactive for somatostatin or NPY synapse mainly on the distal dendrites of pyramidal cells in both the rat and monkey cortex, suggesting that this may be a preferred target of nNOS axons [8], [13]. However, it is not clear how precisely these features describe the nNOS-containing cells, because there is evidence that both somatostatin and NPY are present in other neurons besides nNOS cells [3], [6], [18], [19], [20], [21].
More recently it was shown that nNOS is also present in a smaller and morphologically distinct type of interneuron in the cortex of monkeys, but apparently not in that of rats [1], [12], [27], [28]. In contrast to the large nNOS cells, these small nNOS interneurons express the calcium binding protein calbindin [27], [28]. In the monkey cortex it is unclear whether the small nNOS cells express somatostatin and NPY, as do the large nNOS cells. The purpose of this study in the monkey cortex was to determine how reliably immunoreactivity for somatostatin, neuropeptide Y, and calbindin can be used to differentiate the large and small nNOS cells, and to determine to what extent these markers are found in other neurons besides the nNOS interneurons.
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Materials and methods
Two Macaca nemestrina and one Macaca fascicularis monkeys were used. The nemestrina monkeys were received from the Regional Primate Research Center at the University of Washington, and the fascicularis monkey was housed at the Nathan Kline Institute in accordance with NIH guidelines. All monkeys were transcardially perfused using 4% paraformaldehyde as a fixative as previously described [24]. The right cerebral hemispheres were cryoprotected and sectioned at 40 or 80 μm thickness with a sliding
Results
Two distinct types of interneurons were nNOS-immunoreactive, and these are referred to as LNOS and SNOS neurons (Fig. 1A and B). The LNOS cells were large (196±66 μ2) densely labeled multipolar or bipolar cells which typically had two to six thick dendrites projecting from their cell body. They were especially abundant in the infracortical white matter, and they were also present throughout the cortical gray matter (Fig. 2B). The SNOS cells were consistently smaller (65±16 μ2) and usually more
Discussion
The findings demonstrate that the two types of nNOS interneurons can be distinguished by the differential expression of calbindin, somatostatin and NPY, but that these markers are not found exclusively in nNOS cells. The neurochemical features and distribution of nNOS cells did not vary across cortical areas, suggesting that these cells are a constant component of the cortical circuitry.
Some NPY cells did not contain nNOS-immunoreactivity. These cells had light NPY-immunoreactivity compared to
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