The transmitters acetylcholine and yaminobutyrate (GABA) play critical roles in the formation of receptive-field properties of retinal ganglion cells. In rabbit retina, cholinergic amacrine and displaced amacrine cells were identified by immunohistochemical staining for the enzyme choline acetyltransferase and by their avid accumulation of the fluorescent dye 4',6-diamidino-2-phenylindole. Several GABAimmunoreactive and glutamate decarboxylase-immunoreactive cell types, including a prominent population of small, round amacrine and displaced amacrine cells, were also identified. Double-label experiments demonstrated that all amacrine and displaced amacrine cells that prominently accumulate 4',6-diamidino-2-phenylindole contain GABA and glutamate decarboxylase immunoreactivity. However, not all GABA-immunoreactive cells accumulate this dye. Quantitative analysis of the ganglion cell layer of whole mount preparations of the retina showed that choline acetyltransferase-immunoreactive cells and the majority of GABA-immunoreactive cells have a small, round shape and similar cell density profiles that parallel that of displaced amacrine cells. These studies establish that cholinergic cells are a major subpopulation of GABA-immunoreactive amacrine and displaced amacrine cells. The role these cells have in the formation of ganglion cell receptive-field properties may be parsimoniously explained by an excitatory postsynaptic action mediated by acetylcholine and an inhibitory presynaptic action mediated by GABA.
Retinal ganglion cells are the projection neurons that link the retina to the brain. Peptide immunoreactive cells in the ganglion cell layer (GCL) of the mammalian retina have been noted but their identity has not been determined. We now report that, in the rabbit, 25-35% of all retinal ganglion cells contain substance P-like (SP) immunoreactivity. They were identified by either retrograde transport of fluorescent tracers injected into the superior colliculus, or by retrograde degeneration after optic nerve section. SP immunoreactive cells are present in all parts of the retina and have medium to large cell bodies with dendrites that ramify extensively in the proximal inner plexiform layer. Their axons terminate in the dorsal lateral geniculate nucleus, superior colliculus and accessory optic nuclei, and these terminals disappear completely after contralateral optic nerve section and/or eye enucleation. In the dorsal lateral geniculate nucleus large, beaded, immunoreactive axons and varicosities make up a narrow plexus just below the optic tract, where they define a new geniculate lamina. The varicosities make multiple synaptic contacts with dendrites of dorsal lateral geniculate nucleus projection neurons and presumptive interneurons in complex glomerular neuropil. This is direct evidence that some mammalian retinal ganglion cells contain substance P-like peptides and strongly suggests that, in the rabbit, substance P (or related tachykinins) may be a transmitter or modulator in a specific population or populations of retinal ganglion cells.
This study examined the role and impact of forensic evidence on case-processing outcomes in a sample of 4205 criminal cases drawn from five U.S. jurisdictions. Regression analyses demonstrated that forensic evidence played a consistent and robust role in case-processing decisions. Still, the influence of forensic evidence is time- and examination-dependent: the collection of crime scene evidence was predictive of arrest, and the examination of evidence was predictive of referral for charges, as well as of charges being filed, conviction at trial, and sentence length. The only decision outcome in which forensic evidence did not have a general effect was with regard to guilty plea arrangements. More studies are needed on the filtering of forensic evidence in different crime categories, from the crime scene to its use by investigators, prosecutors, and fact-finders, and to identify factors that shape decisions to collect evidence, submit it to laboratories, and request examinations.
In vitro studies have demonstrated that glia can express functional receptors for a variety of neurotransmitters. To determine whether similar neurotransmitter receptors are also expressed by glia in vivo, we examined the glial scar in the transected optic nerve of the albino rabbit by quantitative receptor autoradiography. Receptor binding sites for radiolabeled calcitonin gene-related peptide, cholecystokinin, galanin, glutamate, somatostatin, substance P, and vasoactive intestinal peptide were examined. Specific receptor binding sites for each ofthese neurotransmitters were identified in the rabbit forebrain but were not detected in the normal optic nerve or tract. In the transected optic nerve and tract, only receptor binding sites for substance P were expressed at detectable levels. The density of substance P receptor binding sites observed in this glial scar is among the highest observed in the rabbit forebrain. Ligand displacement and saturation experiments indicate that the substance P receptor binding site expressed by the glial scar has pharmacological characteristics similar to those of substance P receptors in the rabbit striatum, rat brain, and rat and canine gut. The present study demonstrates that glial cells in vivo express high concentrations of substance P receptor binding sites after transection of retinal ganglion cell axons. Because substance P has been shown to regulate inflammatory and immune responses in peripheral tissues, substance P may also, by analogy, be involved in regulating the glial response to injury in the central nervous system.A major question in neurobiology is why damaged mammalian central nervous system (CNS) neurons do not regenerate in vivo. In recent years, the focus ofattention has shifted from CNS neurons themselves, which appear to have the capacity to regenerate, to CNS glia, which apparently inhibit the regrowth of axons in the CNS. Thus, it has been demonstrated that, after injury, regenerating axons grow a short distance until they reach the glial scar, at which time they appear to stop growing and degenerate (1-6). The major cellular constituent of a CNS glial scar is the reactive astrocyte (4). Unlike fibroblasts, which form scars in nonneural tissue by secreting large amounts of collagenous extracellular matrix, astrocytes form scars by extending numerous processes that become packed with intracellular glial filaments (7). Astrocytes proliferate in response to injury (8), and it appears that these "reactive astrocytes" are biochemically different from the major class of astrocytes present in the normal nonlesioned brain (4). Recently, several neuropeptides, including bombesin, substance K, and substance P, have been shown to be mitogenic (9, 10) for several cell types that may be involved in the inflammatory and wound-healing responses in peripheral tissues (11). In vitro studies suggest that glia are potential targets for a variety of neurotransmitters (12) including substance P (13-16), somatostatin (17, 18), and vasoactive intestinal peptide (15,17...
Peptides have been found in the retinas of all mammalian species studied to date, but little is known about their localization and function in the cat. Using two mouse monoclonal antibodies directed to somatostatin 14, we have observed two sparse groups of somatostatin-immunoreactive neurons in the cat, both distributed preferentially in the inferior retina. The more numerous cell type is characterized by a small- to medium-sized soma (mean diameter = 16.3 +/- 9.0 microns; n = 186) with sparsely branching, far-reaching varicose processes that ramify mainly in the inner plexiform layer. The majority of these cells are located in the ganglion cell layer, with the remainder in the proximal inner nuclear layer and the inner plexiform layer. They are in especially high density at the retinal margin. In morphology and soma size, these cells resemble wide-field amacrine cells. The second cell type has a large, granular-staining soma (mean diameter = 29.7 +/- 14.8 microns; n = 145) with poorly stained primary processes and is found only in the ganglion cell layer. Cells of this type are most similar in their size and morphology to alpha ganglion cells. In contrast to the location of somatostatin-immunoreactive somata, a dense meshwork of immunoreactive processes was observed at all eccentricities within the inner plexiform layer, adjacent to the inner nuclear layer and to the ganglion cell layer. Labeled processes arising from the inner plexiform layer were also occasionally detected in the outer plexiform layer and the nerve fiber layer. Additional processes of unknown origin were observed in the nerve fiber layer and the optic nerve head. The extensive distribution of immunoreactive processes suggests that somatostatin-immunoreactive somata located preferentially in the inferior half of the retina have a widespread influence on neural activity.
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