Biomedical subjects

Sally I Firth

Publications and source records attributed to Sally I Firth.

7 recordsLinked to original sources

PubMed2005

Retinal waves: mechanisms and function in visual system development.

A characteristic feature of developing neural networks is spontaneous periodic activity. In the developing retina, retinal ganglion cells fire bursts of action potentials that drive large increases in intracellular calcium concentration with a periodicity of minutes. These periodic bursts of action potentials propagate across the developing inner retina as waves, driving neighboring retinal ganglion cells to fire in a correlated fashion. Here we will review recent progress in elucidating the mechanisms in mammals underlying retinal wave propagation and those regulating the periodicity with which these retinal waves occur. In addition, we will review recent experiments indicating that retinal waves are critical for refining retinal projections to their primary targets in the central visual system and may be involved in driving developmental processes within the retina itself.

Animals↗

PubMed2004

Screening for differential gene expression during the development of form-deprivation myopia in the chicken.

PURPOSE: To use the technique of differential gene display to analyze changes in gene expression that occur during the development of and recovery from form-deprivation myopia. METHODS: The differential display-reverse transcriptase-polymerase chain reaction technique was used to detect cDNAs that are differentially expressed after 24 h (including 12 h in the light) after fitting with a diffuser to induce form-deprivation myopia. Messenger RNA levels were determined by quantitative Northern blotting in retinas after 11 days of form deprivation or in retinas where the diffusers had been removed the previous day. RESULTS: Twenty-six differentially expressed genes were processed in our initial screen. Two of these, alphaB-crystallin and retinoic acid receptor-alpha, were studied further. Levels of alphaB-crystallin mRNA were increased on day 11 in retinas from form-deprived eyes relative to eyes of control chickens and were reduced to below those levels within 6 to 12 h after removal of the diffusers. Levels of retinoic acid receptor-alpha mRNA showed similar changes, except that after removal of the diffusers, the levels further increased. CONCLUSIONS: The technique of differential gene display can be used to detect changes in gene expression during the regulation of eye growth. The response of alphaB-crystallin is particularly interesting because expression increases when eye growth is high and decreases when eye growth slows.

Aging↗

PubMed2004

Emergence of realistic retinal networks in culture promoted by the superior colliculus.

The developing retina is characterized by 'retinal waves', spontaneous depolarizations that propagate through a developing network of interneurons and retinal ganglion cells. Although the circuitry underlying retinal waves is well characterized, the secreted factors that are critical for its normal development are not defined. Dissociated cell culture provides an ideal system for defining these factors; however, it is difficult to recapitulate retinal circuitry in culture. Here we demonstrate that by culturing dissociated retinal neurons in the presence of cells from the superior colliculus (SC), retinal neurons form networks that are similar to those described in the intact retina. Whole-cell voltage clamp recordings reveal the presence of a spontaneously active network of interneurons. In addition, we observed spontaneous, propagating activity reminiscent of that observed in the intact retina. We propose that the presence of factors secreted from the SC results in the development of networks that reproduce critical features of the intact retina.

Animals↗

PubMed2003

AMPA receptors mediate acetylcholine release from starburst amacrine cells in the rabbit retina.

The light response of starburst amacrine cells is initiated by glutamate released from bipolar cells. To identify the receptors that mediate this response, we used a combination of anatomical and physiological techniques. An in vivo, rabbit eyecup was preloaded with [(3)H]-choline, and the [(3)H]-acetylcholine (ACh) released into the superfusate was monitored. A photopic, 3 Hz flashing light increased ACh release, and the selective AMPA receptor antagonist, GYKI 53655, blocked this light-evoked response. Nonselective AMPA/kainate agonists increased the release of ACh, but the specific kainate receptor agonist, SYM 2081, did not increase ACh release. Selective AMPA receptor antagonists, GYKI 53655 or GYKI 52466, also blocked the responses to agonists. We conclude that the predominant excitatory input to starburst amacrine cells is mediated by AMPA receptors. We also labeled lightly fixed rabbit retinas with antisera to choline acetyltransferase (ChAT), AMPA receptor subunits GluR1, GluR2/3, or GluR4, and kainate receptor subunits GluR6/7 and KA2. Labeled puncta were observed in the inner plexiform layer with each of these antisera to glutamate receptors, but only GluR2/3-IR puncta and GluR4-IR puncta were found on the ChAT-IR processes. The same was true of starburst cells injected intracellularly with Neurobiotin, and these AMPA receptor subunits were localized to two populations of puncta. The AMPA receptors are expected to desensitize rapidly, enhancing the sensitivity of starburst amacrine cells to moving or other rapidly changing stimuli.

Acetylcholine↗

PubMed2002

Innervation of the uvea by galanin and somatostatin immunoreactive axons in macaques and baboons.

The neuropeptide galanin has not been localized previously in the primate uvea, and the neuropeptide somatostatin has not been localized in the uvea of any mammal. Here, the distribution of galanin-like and somatostatin-like immunoreactive axons in the iris, ciliary body and choroid of macaques and baboons using double and triple immunofluorescence labeling techniques and confocal microscopy was reported. In the ciliary body, galanin-like immunoreactive axons innervated blood vessels and the ciliary processes, particularly at their bases. In the iris, the majority of these axons was associated with the loose connective tissue in the stroma. Somatostatin-like immunoreactive axons were found in many of the same areas of the uvea supplied by cholinergic nerves. In the ciliary body, there were labelled axons within the ciliary processes and ciliary muscle. They were also found alongside blood vessels in the ciliary stroma. In the iris, somatostatin-like immunoreactive axons were abundant in the sphincter muscle and less so in the dilator muscle. A unilateral sympathectomy had no effect on the distribution of somatostatin-like or galanin-like immunoreactive axons, and these axons did not contain the sympathetic marker tyrosine hydroxylase. They did not contain the parasympathetic marker choline acetyltransferase, either. The galanin-like immunoreactive axons contained other neuropeptides found in sensory nerves, including calcitonin gene-related peptide, substance P and cholecystokinin. Somatostatin-like immunoreactive axons did not contain any of these sensory neuropeptides or galanin-like immunoreactivity, and they were neither labelled with an antibody to 200kDa neurofilament protein, nor did they bind isolectin-IB(4). Nevertheless, they are likely to be of sensory origin because somatostatin-like immunoreactive perikarya have previously been localized in the trigeminal ganglion of primates. Taken together, these findings indicate galanin and somatostatin are present in two different subsets of sensory axons in primate uvea.

Animals↗

PubMedDate not supplied

Cholecystokinin-like immunoreactive amacrine cells in the rat retina.

High levels of endogenous cholecystokinin (CCK) are present in the rat retina (Eskay & Beinfeld, 1982), but the cellular localization and physiological actions of CCK in the rat retina are uncertain. The goals of this study were to characterize the cells containing CCK, identify cell types that interact with CCK cells, and investigate the effects of CCK on rod bipolar cells. Rat retinas were labeled with antibody to gastrin-CCK (gCCK) using standard immunofluorescence techniques. Patch-clamp methods were used to record from dissociated rod bipolar cells from rats and mice. Gastrin-CCK immunoreactive (-IR) axons were evenly distributed throughout the retina in stratum 5 of the inner plexiform layer of the rat retina. However, the gCCK-IR somata were only detected in the ganglion cell layer in the peripheral retina. The gCCK-IR cells contained glutamate decarboxylase, and some of them also contained immunoreactive substance P. Labeled axons contacted PKC-IR rod bipolar cells, and recoverin-IR ON-cone bipolar cells. CCK-octapeptide inhibits GABA(C) but not GABA(A) mediated currents in dissociated rod bipolar cells.

Amacrine Cells↗

PubMedDate not supplied

Dissociated GABAergic retinal interneurons exhibit spontaneous increases in intracellular calcium.

Early in development, before the retina is responsive to light, neurons exhibit spontaneous activity. Recently it was demonstrated that starburst amacrine cells, a unique class of neurons that secretes both GABA and acetylcholine, spontaneously depolarize. Networks comprised of spontaneously active starburst cells initiate correlated bursts of action potentials that propagate across the developing retina with a periodicity on the order minutes. To determine whether other retinal interneurons have similar "pacemaking" properties, we have utilized cultures of dissociated neurons from the rat retina. In the presence of antagonists for fast neurotransmitter receptors, distinct populations of neurons exhibited spontaneous, uncorrelated increases in intracellular calcium concentration. These increases in intracellular calcium concentration were sensitive to tetrodotoxin, indicating they are mediated by spontaneous membrane depolarizations. By combining immunofluorescence and calcium imaging, we found that 44% of spontaneously active neurons were GABAergic and included starburst amacrine cells. Whole cell voltage clamp recordings in the absence of antagonists for fast neurotransmitters revealed that after 7 days in culture, individual retinal neurons receive bursts of GABA-A receptor mediated synaptic input with a periodicity similar to that measured in spontaneously active GABAergic neurons. Low concentrations of GABA-A receptor antagonists did not alter the inter-burst interval despite significant reduction of post-synaptic current amplitude, indicating that pacemaker activity of GABAergic neurons was not influenced by network interactions. Together, these findings indicate that spiking GABAergic interneurons can function as pacemakers in the developing retina.

2-Amino-5-phosphonovalerate↗