Biomedical subjects

I G Morgan

Publications and source records attributed to I G Morgan.

At least 37 records · Page 2Linked to original sources

PubMed1994

A role for the enkephalin-immunoreactive amacrine cells of the chicken retina in adaptation to light and dark.

The functional state of the amacrine cells which contain enkephalin-, neurotensin- and somatostatin-like immunoreactivity of the chicken retina was monitored by measuring the rate of change in the levels of [Leu]enkephalin-like immunoreactivity in the retina. Dark-adapted birds were exposed to lights of different intensities for 12 h. At light levels of < or = 0.03 microW/cm2, the ENSLI amacrine cells were highly active but, by 0.08 microW/cm2, they reached a state of maximum inactivation. Thus, the ENSLI amacrine cells act as flip-flop devices, inactivated by critical levels of light, which correspond to those which inactivate pineal melatonin synthesis. They may, therefore, be involved in retinal pathways which signal the difference between day and night.

Adaptation, Physiological↗

PubMed1994

Endogenous dopamine inhibits the release of enkephalin-like immunoreactivity from amacrine cells of the chicken retina in the light.

The activity of the enkephalin-immunoreactive (ENSLI) amacrine cells of the chicken retina is low in the light and high in the dark, resulting in parallel increases and decreases in the levels of the enkephalins. In vivo, the selective dopaminergic D1 antagonist SCH23390 increased the activity of the ENSLI amacrine cells in the light (ED50; 20 pmol), but had a much lesser effect in the dark, whereas the selective dopaminergic D2 antagonist sulpiride had effects only at very high concentrations (ED50; 39 nmol). In contrast, the non-selective dopamine agonist ADTN hardly affected the activity of the ENSLI amacrine cells in the light, but markedly reduced their activity in the dark. This pattern of effects suggests that dopamine actively inhibits the ENSLI amacrine cells in the light, but exerts much less inhibitory activity in the dark, consistent with the idea that dopamine is released during the exposure of the retina to light. Thus dopaminergic controls over the ENSLI amacrine cells appear to contribute to the light:dark differences in activity of the ENSLI amacrine cells. Results obtained on the dopaminergic control of enkephalin release in vitro were generally consistent with this model, except that ADTN appeared to stimulate the ENSLI amacrine cells in the dark.

Animals↗

PubMed1994

Somatostatin-14 and somatostatin-28 levels are light-driven and vary during development in the chicken retina.

The relative levels of somatostatin-14 and somatostatin-28 were determined during both perinatal development and variations in lighting conditions in the chicken retina. During perinatal development of the retina, somatostatin-14 predominated in recently hatched chickens, whereas somatostatin-28 predominated in the retinas of older chickens. In mature chickens, the levels of both somatostatin-14 and somatostatin-28 increased during the light and decreased during the dark. Our results suggest that these two forms of somatostatin are released proportionally and in parallel.

Aging↗

PubMed1994

Is nitric oxide a transmitter of the centrifugal projection to the avian retina?

The chicken retina contains a population of prominent elements in the inner nuclear layer, which stain for NADPH-diaphorase. In distribution and morphology, these elements resemble the terminals of the centrifugal projection from the isthmo-optic nucleus. This identification was confirmed by showing that the NADPH-diaphorase-positive elements in the retina degenerated after destruction of the isthmo-optic nucleus or tract. These results indicate that the centrifugal projection to the retina in birds uses nitric oxide as a messenger or transmitter, in addition to a more conventional but as yet unidentified transmitter.

Animals↗

PubMed1993

[Leu5]enkephalin-like immunoreactive amacrine cells are under nicotinic excitatory control during darkness in chicken retina.

Based on the principle that retinal levels of [Leu5]enkephalin-like immunoreactivity (LELI) are set by the rate of release and thus reflect neural activity, we partially defined the dark-associated increase in excitatory control of LELI amacrine cells in chicken. Retinal levels of LELI were measured by radioimmunoassay (RIA). Intravitreal injection of cholinergic antagonists decreased the rate of depletion of LELI during the dark phase, suggesting the presence of cholinergic excitatory control of the LELI neurons. This cholinergic control involves nicotinic rather than muscarinic receptors, as tubocurarine appeared over 100 times more effective than atropine in inhibiting the decrease in retinal levels of LELI in the dark. (The ED50s were estimated at 3.2 and 450 nmol, respectively.) The lack of effect of the antagonists when applied during the light phase, suggest that there is little cholinergic input to the LELI amacrine cells in the light. Superfusing isolated retinas with buffer containing tubocurarine (10 microM) decreased the efflux of LELI by 35%, compared to the spontaneous release during the dark. Atropine (10 microM) had no effect on the release of LELI, and pilocarpine (100 microM) increased the release of LELI from retinas superfused in the light by 20%. We conclude that, in addition to previously reported glycinergic and dopaminergic inhibition, the LELI amacrine cells receive cholinergic excitatory input. A shift in balance between glycinergic and dopaminergic inhibitory, and cholinergic excitatory control may underly the light-driven variation in activity of the LELI neurons in chicken retina.

Animals↗

PubMed1991

Glycinergic control of [Leu5]enkephalin levels in chicken retina.

Retinal levels of [Leu5]enkephalin-like immunoreactivity (LE-LI) increase during the light and decrease during darkness, in vivo15. Intravitreal injection of the GABA antagonist picrotoxin had no effect on the accumulation of LE-LI during the light, suggesting the absence of significant GABAergic control over LE-LI cells. However, injection of the glycine antagonist strychnine, prevented the light-induced increase of retinal levels of LE-LI during 6 h exposure to light, indicating the presence of glycinergic control over the LE-LI neurons. When applied during the dark, strychnine increased the depletion of LE-LI by 34% compared to vehicle-injected eyes, suggesting that the LE-LI neurons receive some glycinergic input during the dark as well. The release of LE-LI from retinas superfused in vitro is depressed by exposing the preparation to light. Superfusing isolated retinas with physiological buffer containing picrotoxin (100 microM), GABA (50 mM), or the GABA agonists muscimol (100 microM), (+)-baclofen (200 microM), or 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol (THIP) (100 mM), had no effect on the efflux of LE-LI. Strychnine (100 mM) however increased the efflux of LE-LI by 64%, compared to the spontaneous efflux during the light. Glycine (15 and 50 mM) decreased the spontaneous efflux of LE-LI from retinas superfused in darkness by 44-48% and by 31% at 5 mM. These data are consistent with the results from pharmacological manipulations in vivo. We conclude that the LE-LI amacrine cells are under inhibitory control from glycinergic but not from GABAergic neurons.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

Thy-1 antigen is specific to ganglion cells in chicks.

The cellular localization of Thy-1 in the chick retina was investigated by selectively destroying certain populations of neurons with toxins. In control retinae four weeks after intravitreal injection of vehicle, there was strong immunoreactivity for Thy-1 in the nerve fibre layer, ganglion cell layer and inner plexiform layer. By contrast, 4 weeks after intraocular injection with 1.25 nmol of colchicine, virtually all ganglion cells had been destroyed, but most amacrine cells remained. Very little Thy-1 immunoreactivity was evident in these retinae. Four weeks after intraocular injection of 2 mumol of N-methyl-D-aspartic acid (NMDA), a large proportion of amacrine cells had been destroyed, but most ganglion cells remained. In these retinae Thy-1 immunoreactivity was present in the nerve fibre, ganglion cell and inner plexiform layers, in the latter with greater intensity than in controls. We conclude that in chicks the Thy-1 antigen is principally, if not exclusively restricted to ganglion cells.

Animals↗

PubMed1991

How peptidergic neurons cope with variation in physiological stimulation.

A general scheme for neuropeptide metabolism is outlined and the potential sites of regulation are discussed. Two major sites of regulation are distinguished: transcription which ultimately limits the rate of translation to form the prepropeptide, and post-translational processing steps. The consequences of up-regulation of these steps in response to increased metabolic demand are discussed. An alternative strategy for peptidergic neurons, reliance on a large pool of neuropeptide, is proposed. Data on the response of enkephalin-containing cells to increased levels of stimulation are reviewed. It is concluded that there is good evidence for genomic up-regulation, perhaps in association with regulation of processing. Evidence based on studies on enkephalin-containing amacrine cells in the chicken retina is also reviewed. It is suggested that these cells rely on a large pool of neuropeptide to cope with changes in demand.

Animals↗

PubMed1990

Selective abolition of OFF responses in kainic acid-lesioned chicken retina.

When ganglion cell responses were recorded from optic axons in the superficial layers of the chicken optic tectum, the responses recorded are predominantly ON-OFF transient, with some ON transient, and rare OFF transient responses. Several weeks after excitotoxic lesion of the retina with 40 nmol of kainic acid injected intravitreally, only ON transient responses could be recorded from the contralateral optic tectum. ON response latency and threshold were not affected. At low light intensities responses in the kainic acid-lesioned retinas showed a sustained component which was not detected in control retinas, but at high light intensities, the sustained component disappeared and the responses were extremely transient. The disappearance of the OFF responses seems to be due to elimination of the OFF component of the responses of cells which are normally ON-OFF transient, rather than the silencing of these cells, leaving only the normally ON transient cells. Morphological evidence suggests that approximately two thirds of the bipolar cells and most amacrine cells are destroyed by the kainic acid lesion (Ingham and Morgan, Neuroscience, 9 (1983) 165-181), and pharmacological logic (Morgan, Prog. Retinal Res., 2 (1983) 247-266) suggests that the missing bipolar cells should be OFF bipolar cells. These results therefore suggest that ON-OFF transient cells receive direct input from bipolar cells, which determines their basic response type. These results also suggest that amacrine cells have little if any role to play in the generation of the basic centre responses of these ON-OFF transient ganglion cells, and that while amacrine cells may have a role in the generation of transient responses in the inner plexiform layer, transient responses can be generated without the intervention of amacrine cells, particularly at high intensities.

Animals↗

PubMed1990

Identification of kainic and quisqualic acid receptors on inner retinal cells of the salamander Ambystoma mexicanum.

The presence of kainic (KA) and quisqualic acid (QA) receptors on inner retinal neurones of the axolotl Ambystoma mexicanum has been studied using intracellular recording techniques. In the presence of CoCl2, which blocks neurotransmitter release, KA and QA depolarized the membrane. The minimum concentration of KA that induced a response was 1 microM and a maximum response was obtained with 10 microM (EC50: 3 microM). The operating range of QA was between 0.5 and 5 microM with an EC50 of 1 microM. These data show that inner retinal cells of the axolotl are sensitive to KA and QA. Cis-2,3-piperidine dicarboxylic acid (PDA, 3 mM) completely blocked responses to 5 microM KA, but not those induced by 2 microM QA. This suggests that the KA- and QA-sensitive receptors on inner retinal cells of the salamander are pharmacologically different and that PDA can be a valuable tool in distinguishing KA- and QA-sensitive receptors on these neurones.

Ambystoma↗

PubMed1990

Light inhibits the release of both [Met5]enkephalin and [Met5]enkephalin-containing peptides in chicken retina, but not their syntheses.

The levels of native and cryptic [Met5]enkephalin in the chicken retina were found to vary during a 12:12 h light-dark cycle, both rising in the light and falling during the dark. Such variations could conceivably arise from (a) changes in the rate of release and subsequent degradation of native and/or cryptic [Met5]enkephalin, (b) changes in the rate of proenkephalin A synthesis, or (c) changes in the rate of proenkephalin A processing. Measurement of the rate of release of native and cryptic [Met5]enkephalin in vitro indicated that the increased rate of release of both of these forms of [Met5]enkephalin during the dark quantitatively accounted for the fall in their retinal levels during the dark. This indicated that the biosynthesis of proenkephalin A was not activated during the light-dark cycle. Molecular weight fractionation of retinal extracts also supported this idea, since the pool of high molecular weight precursors did not vary in size, suggesting that processing was not modulated during the light-dark cycle. Instead, the fall in both cryptic and native [Met5]enkephalin during the dark was due to their increased rate of release together with a rate-limiting conversion of high molecular weight [Met5]enkephalin-containing peptides to low molecular weight [Met5]enkephalin-containing peptides. The enkephalinergic cells of the retina seem to cope with physiological variations in demand by accumulating a large pool of peptide during periods of low stimulation (light), so that when stimulation and release is high (dark), the decrease in pool levels does not compromise the function of the cells and their postsynaptic targets.

Animals↗

PubMed1990

A quantitative analysis of the effects of excitatory neurotoxins on retinal ganglion cells in the chick.

The present study examines the differential effects of three excitotoxins, kainic acid (KA), N-methyl-D-aspartate (NMDA), and alpha-amino-2,3-dihydro-5-methyl-3-oxo-4-isoxazolepropanoic acid (AMPA) on neurons within the ganglion cell layer (GCL) of the chick retina. Two-day-old chicks were given a single, 5 microliters, intravitreal injection of KA, NMDA, or AMPA at a range of doses. Following treatment with 40 nmol KA, there was a 21% loss of neurons in the GCL. At 200 nmol KA, the loss increased to 46%. Exposure to KA eliminated mainly small neurons of soma area 5-15 microns2, and medium-sized ganglion cells of soma area 15-25 microns2. Large ganglion cells (greater than 25 microns2) remained unaffected. The vast majority of small cells were probably displaced amacrine cells. Exposure to 400 nmol NMDA resulted in a 14% loss of neurons, predominantly involving the large ganglion cells. At a dose of 3000 nmol NMDA, no further loss of cells was evident. Exposure to 200 nmol AMPA resulted in a 30% loss of large and some medium-sized ganglion cells. In a further series of experiments, exposure to excitotoxin was followed by a retinal scratch, which eliminated retinal ganglion cells within the axotomized region. The results indicate that only a small proportion of displaced amacrine cells are destroyed by NMDA and AMPA, whereas virtually all displaced amacrine cells are sensitive to KA. The findings of this study indicate the existence of subclasses of ganglion cells with specificity towards different types of excitatory amino acids (EAA).

Animals↗

PubMed1989

Co-lamination of cholinergic amacrine cell and displaced ganglion cell dendrites in the chicken retina.

Displaced ganglion cells in the chicken retina were back-labelled with Fast blue injected into the nucleus of the basal optic root, then filled under visual control with Lucifer yellow to reveal the dendritic fields of the cells. In transverse sections, the dendrites of the displaced ganglion cells formed a narrow band in the outer part of the inner plexiform layer. Counter-staining for acetylcholinesterase (AChE) activity showed that the dendrites of the displaced ganglion cells and the type I cholinergic amacrine cells co-laminated in the outer part of the inner plexiform layer.

Acetylcholinesterase↗

PubMed1988

Putative serotonergic bipolar and amacrine cells in the chicken retina.

Four populations of putative serotonergic cells could be detected in the chicken retina by histofluorescence and immunohistochemistry. Numerous (10,000/mm2) small (6 micron diameter) bipolar cells were located towards the middle of the inner nuclear layer, as were sparser (1000/mm2) larger (12 micron diameter) amacrine cells. Very sparse large (greater than 30 micron diameter) and more numerous small (12 micron diameter) ganglion cells were also detected. Prominent fibre plexuses were detected in the inner plexiform layer, close to the inner nuclear and ganglion cell layers, and appeared to be formed by the processes of the bipolar cells, amacrine cells and at least the large ganglion cells. Exogenous serotonin (5-HT) was detected in the chicken retina. From the effects of neurotoxins on 5-HT levels and 5-HT-like immunoreactivity (5-HTLI), most of this appeared to be associated with the amacrine cells. 5-HTLI bipolar cells were selectively destroyed by intravitreal injections of 5-10 nmol of kainic acid, while 5-HTLI amacrine cells were destroyed by N-methyl-D,L-aspartic acid and 5,7-dihydroxytryptamine. The sensitivity of the bipolar cells to kainic acid indicates that they are OFF-cells.

5,7-Dihydroxytryptamine↗

PubMed1987

Intravitreal kainic acid severely reduces the size of the developing optic tectum in newly hatched chickens.

Following a single intravitreal injection of 200 nmol of kainic acid (KA) to newly hatched chickens, there are acute and long-term effects on retinal ganglion cells in the chicken retina. Thirty min after injection, most ganglion cells showed cytoplasmic vacuolization. However, 14 days later, most ganglion cell soma appeared normal. Almost 60% of the cells in the ganglion cell layer (GCL) were lost, suggesting that displaced amacrine cells and not more than 40% of the ganglion cells had been eliminated. Following intravitreal injection of wheat germ agglutinin conjugated to horseradish peroxidase 14 days after the KA lesion, the amount of HRP reaction product was reduced in all retinorecipient layers, especially layers IIc and IId, of the tectum contralateral to the KA-treated eye. Fourteen days after the injection of kainic acid, during which the control tecta grow appreciably, all the superficial layers of the tectum contralateral to the kainic acid-lesioned eye, especially layers IIc and IId, were smaller than in controls, and did not differ in size from those seen in tecta contralateral to cut optic nerves. It is not clear whether this is a result of a developmental failure, or a shrinkage, or a combination of these factors. These results suggest that subtypes of ganglion cells may have a disproportionate influence in the maintenance of the cytoarchitectural integrity in the optic tectum. Alternatively the removal of the OFF-bipolar cells and amacrine cells presynaptic to ganglion cells may decrease their metabolism, and restrict the supply of trophic influences to the developing tectal cells.

Aging↗

PubMed1987

AMPA is a powerful neurotoxin in the chicken retina.

Intravitreal (RS)-alpha-amino-3-hydroxy-5-methyl-4-isoxazoleacetic acid (AMPA) is a powerful excitotoxin on the chicken retina. Doses of 10 nmol/eye produce half-maximum destruction of cholinergic amacrine cells, making AMPA equipotent with kainic acid. The effects of AMPA can be distinguished from those of kainic acid morphologically, and from those of N-methyl-D-aspartic acid by the failure of 2-amino-5-phosphonopentanoic acid (2-AP5) to block those of AMPA. Both morphologically, and in response to 2-AP5, the effects of AMPA and quisqualic acid are indistinguishable, but AMPA is much more potent than quisqualic acid, presumably due to the uptake and inactivation of quisqualic acid.

Animals↗

PubMed1987

Specific ganglion cell death induced by intravitreal kainic acid in the chicken retina.

In young chickens, intravitreal kainic acid (60 nmol) causes axonal and terminal degeneration in some retinorecipient areas of the chicken brain. The accessory optic nuclei are markedly affected, suggesting that the large displaced ganglion cells are destroyed by kainic acid, and a specific pattern of degeneration is caused in the optic tectum, which suggests that other minor ganglion cell groups may also be sensitive to intravitreal kainic acid.

Animals↗

PubMed1987

Localization of choline acetyltransferase-like immunoreactivity in the embryonic chick retina.

Putative sites of acetylcholine synthesis in the retina of the embryonic and posthatched chick were localized immunohistochemically with antisera to choline acetyltransferase; the resultant choline acetyltransferase-like immunoreactivity (ChAT-IR) was compared to demonstrated sites of acetyltransferase (AChE) activity, and changes were followed in localization during development. The results confirmed the early and rapid course of development of the chick's retinal cholinergic system described in previous biochemical and morphological studies. Immunoreactivity was first detected at embryonic day 6.5 in cells close to the retina's vitreal surface. By 8 days it was present in cells in two juxtaposed rows; by the ninth day the two rows were separated and immunoreactivity was evident in two subliminae of the inner plexiform layer. On the tenth day distribution was like that in the posthatched chicken, in type I cholinergic cells in the inner nuclear layer and in type II cells in the ganglion cell layer (Millar et al.: Neurosci. Lett. 61:311-316, '85), and similar to that of most vertebrates. Three days before hatching, a third population of weakly immunoreactive cells (type III cells) appeared within the inner nuclear layer. The onset of localizable ChAT-IR occurred in amacrine cells and in their processes, before the period of synaptogenesis. Acetylcholinesterase activity was localized at an earlier age than ChAT-IR, and at all ages was present in more cells. The results obtained support the view that "displaced" cholinergic amacrine cells begin to differentiate at the same time and in the same retinal region as type I cholinergic cells. Separation of the two groups is a consequence of the ramification of processes of amacrine and ganglion cells rather than a result of the secondary migration of cells between layers.

Acetylcholinesterase↗