, 1996). Future experiments on the ultrastructural localization of neuropeptide receptors may show similar sites of expression at specific regions of the plasma membrane. The classic view that neuropeptide-containing neurons represented an unusual type of neuron is giving way to the perspective that many, perhaps most neurons in the brain, probably contain some neuropeptide(s) or other neuromodulator in addition to fast-acting amino acid neurotransmitters. In an examination of individual
sections containing synaptic boutons with electron microscopy, with the boutons fixed to preserve the dense core of vesicles, some boutons appeared to contain only clear vesicles, others contained clear and DCVs. However, serial ultrathin section reconstruction of GABA-immunogold-labeled presynaptic boutons selleck from the paraventricular nucleus demonstrated that every bouton contained at least see more a few dense core vesicles, suggesting that in addition to a fast amino acid transmitter, most if not all GABAergic axons here also contained some neuromodulator (Decavel and van den Pol, 1990). Release and actions of these neuromodulators remains to be demonstrated. Furthermore, because the axons studied contained GABA which is not found in magnocellular neurons, the profiles could not arise from the local
oxytocin or vasopressin neurosecretory cells. Similarly, presynaptic boutons showing no immunogold GABA labeling, many of which were probably glutamatergic, also showed a similar
frequency of DCVs in boutons, interspersed with small clear vesicles. A complication to the detection of DCVs with electron microscopy is that the dense core can be lost by suboptimal fixation pH, duration, chemistry, and osmotic pressure (Morris and Cannata, 1973), complicating detection in some studies and biasing results toward Oxygenase a false-negative lack of detectable DCVs. A related question is whether all peptidergic axons also contain a fast amino acid transmitter. Most evidence, including that based on immunocytochemistry, calcium digital imaging, and electrophysiology supports the perspective that the great majority of peptidergic cells also employ fast amino acid transmitters (van den Pol, 1991, 2003; van den Pol et al., 1990; van den Pol and Trombley, 1993; Freund and Buzsáki, 1996). Whereas hypothalamic neurons have long been recognized as utilizing a large number of peptides, other regions of the brain are now being seen as not substantively different in this regard. For instance, in the hippocampus, a region with a rich history in the study of fast GABA and glutamate transmission, a plethora of neuropeptides are synthesized, particularly by GABAergic inhibitory interneurons, including neuropeptide Y, somatostatin, vasoactive intestinal polypeptide, cholecystokinin, dynorphin, enkephalin, neurokinin B, and substance P (Acsády et al., 1996, 2000; Billova et al., 2007; Antonucci et al.