Cholecystokinin-immunoreactive neurons in rat and monkey cerebral cortex make symmetric synapses and have intimate associations with blood vessels.

Abstract

Neurons displaying cholecystokinin-like immunoreactivity (CCK neurons) in rat and monkey cerebral cortex were examined by light and electron microscopic immunocytochemistry. CCK neurons were found to be mainly bipolar cells present in all layers and in all areas of the rat cerebral cortex. CCK neurons were also found in all regions examined in monkey cortex (preand post-central gyri and superior parietal lobule). The somata and the dendritic processes of CCK neurons receive relatively few synapses but both symmetric and asymmetric axosomatic and axodendritic synapses were found. The majority of axon terminals displaying CCK-like immunoreactivity formed symmetric synapses, most frequently with the somata and proximal dendrites of pyramidal and nonpyramidal neurons. The somata and processes of CCK neurons were also found to establish very close nonsynaptic associations with blood vessels and with other neurons, suggesting possible roles for the peptide in the maintenance of neuronal excitability and cerebral blood flow.The octapeptide cholecystokinin (CCK) is one of several neuropeptides that has been identified in the mammalian cerebral cortex (1-3). The localization of CCK in synaptic vesicle fractions of brain homogenates (4), its release from in vitro preparations in a calcium-dependent manner (4), and its excitatory effect on hippocampal (5) and cortical neurons (6) are consistent with the suggestion that the peptide functions as a neurotransmitter in the cortex and elsewhere. However, CCK has yet to be localized at the fine structural level in the cerebral cortex. Cortical neurons displaying CCK-like immunoreactivity have been identified light microscopically in the rat (7,8) but the nature of their pre-and post-synaptic relationships with other neurons are unknown. In the present study, we have used a well-characterized antiserum against CCK-8 (9) to examine the distribution, morphology, and synaptology of neurons that have CCK-like immunoreactivity (CCK neurons) in the cerebral cortex of both rats and monkeys. We show that, in addition to having many of the characteristics of typical local circuit neurons, CCK neurons in the cortex have unusual nonsynaptic relationships with other neurons and with blood vessels. MATERIALS AND METHODSTwo cynomolgus monkeys (Macaca fascicularis; Hazelton Research Primates, Reston, VA) and eight Wistar rats (bred in our colony)-were used. One monkey and three rats received intraventricular injections of colchicine (10 ug/,41; 110 /.l for the monkey, 10 or 15 /ul for the rats) and were allowed to survive for 2 days. All animals were perfused through the heart with 4% paraformaldehyde/0. 1% glutaraldehyde in 0.1 M phosphate buffer (pH 7.4). The rat brains and blocks of monkey brains including the pre-and post-central gyri and the superior parietal lobule were sectioned with either a Vibratome or a freezing microtome at 40-50 ,um. After several washes in 0.1 M phosphate buffer, the sections were incubated overnight in primary antiserum at dilutions of 1:1,000, 1:250, or...

Heterogeneity of GABAergic cells in cat visual cortex

“…There seems to be general agreement that the CCK-, CRF-, and VIP-positive cells occur mainly in the supragranular layers in the rat and cat visual cortex (McDonald et al, 1982b, c;Merchenthaler et al, 1982;Hendry et al, 1983a;Peters et al, 1983;Swanson et al, 1983;Connor and Peters, 1984;Magistretti et al, 1984;Merchenthaler, 1984;Morrison et al, 1984;Magistretti and Morrison, 1985). It seems that the distribution of CRF-positive neurons is somewhat more widespread in the rat than the cat visual cortex, since a number of CRF-positive neurons have been reported outside layers I-II in the rat.…”

“…VIP-containing bipolar neurons constitute the main group ofpeptide-positive cells, which do not contain GAD. In addition, a small subset of CCK-positive bipolar cells can also belong to this group (Hendry et al, 1983a). These 2 groups of bipolars share the common feature of making synaptic contact with blood vessels, as well as with other cortical cells.…”

Non-neural electrical responses of smooth muscle cells of the rabbit basilar artery to electrical field stimulation.

“…Therefore, these biologically active substances may not be involved in generation of the depolarizing response in the rabbit basilar artery. Peptides-containing nerves are also located in cerebral arteries (HENDRY et al, 1983), and transmission from these nerves to the smooth muscle cannot be blocked by the above-mentioned agents. The T.…”

Neurotransmitters Regulate Energy Metabolism in Astrocytes: Implications for the Metabolic Trafficking between Neural Cells

“…Unequivocal evidence at the ultrastructural level indicates the intimate apposition, and in some cases the presence of true synapses, between neurotransmittercontaining profiles and intraparenchymal brain capil laries. In particular this has been demonstrated for VIP [10,11], acetylcholine [10], cholecystokinin [12,13] and NA [14,15]. In addition, pharmacological studies have demonstrated the presence of receptors for NA and VIP, coupled to cAMP-generating systems [16][17][18] in intra parenchymal microvessel preparations.…”