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Biomedical subjects

M R Bennett

Publications and source records attributed to M R Bennett.

At least 199 records · Page 11Linked to original sources
PubMed1990

Chronic necrotizing pulmonary aspergillosis treated by endobronchial amphotericin B.

Chronic necrotizing pulmonary aspergillosis is an indolent, locally invasive form of Aspergillus infection. Treatment options are limited and controversial. Resection is often curative if the patient has sufficient ventilatory reserve. Even though intravenous amphotericin B is effective in a few patients, toxicity limits its use. Aerosolized amphotericin B has proven ineffective. Anecdotal reports of intracavitary and endobronchial antifungal therapy show limited success. Our patient had unresectable chronic necrotizing pulmonary aspergillosis treated successfully with intracavitary instillation of amphotericin B, delivered via the flexible fiberoptic bronchoscope.

Amphotericin B↗
PubMed1990

A retinal ganglion cell neurotrophic factor purified from the superior colliculus.

Dissociated neonatal rat retinal ganglion cells can be maintained by the addition of an extract from the neonatal superior colliculus. This extract can support 95% of ganglion cells over 24 h in culture; in addition it promotes the expression of neurites from these cells. This report describes the purification of a neurotrophic factor from the superior colliculus which supports the survival of 80% of retinal ganglion cells over 24 h in vitro. The purification procedure involves a combination of dye-ligand, anion-exchange, and molecular sieve chromatography. The purified neurotrophic factor has a Stokes radius of approximately 200 A using molecular sieve chromatography in the presence of a chaotropic agent. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the purified factor indicates that it is a glycoprotein that migrates with a molecular mass greater than 400 kDa. Further characterization of this high-molecular-mass glycoprotein by enzymatic digestion demonstrated that it is a chondroitin sulfate proteoglycan. This factor is clearly distinguishable from other neurotrophic factors that have an effect on retinal ganglion cells such as brain-derived neurotrophic factor and fibroblast growth factor. The chondroitin sulfate proteoglycan from the neonatal superior colliculus is the first proteoglycan to be identified as a neurotrophic factor.

Animals↗
PubMed1989

Compartmental and topographical distributions of axons in nerves to the amphibian (Bufo marinus) glutaeus muscle.

The present work seeks to determine if axons to an amphibian muscle are segregated in nerve trunks between the spinal cord and muscle according to their primary nerve destination or their topographical projection in the muscle. The distribution of axons to different compartments and subcompartments of the amphibian (Bufo marinus) glutaeus muscle has been determined in transverse sections of spinal and limb nerves after retrogradely labelling the axons with horseradish peroxidase. Glutaeus axons were dispersed widely through spinal nerves 8 and 9 but loosely gathered together in one quadrant of the sciatic nerve after passing through the lumbar plexus. Glutaeus axons became tightly clustered to the exclusion of other axons along the length of the triceps femoris nerve after it divides from the sciatic nerve. Furthermore, axons destined for one of the two glutaeus primary nerve branches segregate from those of the other branch at the level of the triceps femoris nerve before the glutaeus nerve forms. On the other hand, motoneurones that subserve a primary branch are not segregated, but are found throughout the rostrocaudal extent of the glutaeus motoneurone pool. Injection of horseradish peroxidase under the epimysium of either the ventral or the dorsal surfaces of the glutaeus muscle labelled motoneurones preferentially in either the rostral or caudal part of the motoneurone pool, respectively. This confirms studies that have shown a topographical projection from the spinal motoneurone pool onto the glutaeus muscle. However, there was no segregation of dorsally projecting axons in the glutaeus and primary nerve branches. Thus, glutaeus axons segregate according to their muscle compartmental projections well before entering the muscle, but they show no organization in nerves with respect to their topographical projections within a compartment.

Animals↗
PubMed1989

Growth and elimination of nerve terminals at synaptic sites during polyneuronal innervation of muscle cells: a trophic hypothesis.

This paper examines the possibility that the elimination of synapses from cells arises from a competition between the nerve terminals for trophic molecules made available by the cells. This idea is applied to the elimination of synapses that occurs during the polyneuronal innervation of muscle cells which accompanies both the development and reinnervation of muscles. In the proposed model, each motorneuron makes the same amount of receptor in its soma for a trophic molecule provided in limited quantities by each muscle cell; this receptor is then distributed to the collateral terminals of the motorneuron in concentrations proportional to the amount of receptor made in the soma by the motorneuron; the more collateral terminals initially possessed by a motorneuron the less will be their concentration of receptor. The receptors in the several collateral terminals on a muscle cell then compete for the trophic molecule provided by the muscle, and terminal growth is proportional to the number of receptor-trophic-molecule bonds formed. An autocatalytic effect has been introduced whereby the increase in size of a terminal accelerates the rate by which the trophic molecule is made available to that terminal for bonding with its receptors. In addition, the affinity between nerve terminal receptors and muscle molecules can be varied in the model. Finally, motorneuron cell death has been analysed as the elimination of neurons that have insufficient terminal area to take up a growth factor in amounts that will allow for the survival of the neuron.

Animals↗
PubMed1989

The distribution of intracellular acetylcholine receptors and nuclei in developing avian fast-twitch muscle fibres during synapse elimination.

The spatial distribution of intracellular acetylcholine receptors along the length of fibres from the avian posterior latissimus dorsi muscle has been investigated during embryonic development, when distributed synaptic sites are eliminated from the muscle fibres. Cell surface AChR were irreversibly blocked with unlabelled alpha-bungarotoxin (alpha-BGT). Muscles were then fixed and ultrasonically dissociated into fibre fragments, treated with 0.5% saponin and stained with 125I-alpha-BGT. This revealed an intracellular pool of curare sensitive binding sites equivalent to about 10% of total cell AChR. The spatial distribution of this pool was studied by autoradiography. Large (longer than 2 microns) AChR-clusters (AChR-C) characteristic of neuromuscular contacts were localized on the same fibres by immunofluorescence with an anti-AChR antibody. At E11, relatively high levels of intracellular AChR were observed throughout the length of fibres. Between E11 and E18 intracellular AChR declined (19 fold) in extrajunctional parts of fibres but remained high in segments of fibre corresponding to AChR-clusters. Treatment of E14 embryos with an inhibitor of protein synthesis (cycloheximide) reduced intracellular AChR to 22 +/- 6% (mean +/- SE) of control levels, suggesting that most of the intracellular binding represented newly-synthesized AChR. Between E11 and E18 cell nuclei were found to accumulate beneath AChR-C. The mean density of nuclei in segments of fibre corresponding to AChR-C increased 5 fold between E11 and E18, but remained unchanged in extrajunctional segments. It is suggested that the elimination of excess distributed AChR-C may be due to the preferential accumulation of nuclei at a single AChR-C on each fibre accompanied by the down regulation of AChR synthesis associated with nuclei at the remaining AChR-C.

Animals↗
PubMed1989

The development of topographical maps and fibre types in toad (Bufo marinus) glutaeus muscle during synapse elimination.

1. The toad glutaeus muscle consists of two muscle compartments. A study has been made of the topographical distribution of motor units in these compartments, in relation to the fibre types which arise during different stages of development. 2. Monoclonal antibodies to myosin allowed the distribution of fibre types to be determined. In mature muscles (from toads of greater than 30 g body weight) clusters of type 5 (tonic) fibres were found exclusively at the dorsal surface of the muscle, surrounded by a layer of type 3 (slow-twitch) fibres. A homogeneous layer of type 2 (fast-twitch red) fibres was found beneath this dorsal rind of slow and tonic fibres. The rest of the muscle, including the ventral surface, consisted of a mosaic of type 1 (fast-twitch white) and type 2 fibres. 3. Glycogen-depletion methods, together with the myosin antibodies, allowed the distribution of single motor units and their fibre types to be determined. In mature muscles, axons originating from rostral spinal cord possessed muscle units located in a band extending from the ventral surface to beyond the middle of the muscle; these units consisted of 78% type 1 and 22% type 2 fibres found amongst the mosaic of type 1 and type 2 fibres. Intermediate axons possessed muscle units located primarily in the middle and dorsal half of the muscle. These units consisted mostly of type 2 fibres (29% type 1, 71% type 2) also found amongst the mosaic of type 1 and type 2 fibres. Thus rostral and intermediate units were of mixed fibre type, with type 1 fibres predominating in the former units and type 2 in the latter. Caudal axons possessed muscle units located mostly in the homogeneous layer of type 2 fibres, beneath the dorsal rind of tonic fibres; these units were almost always composed entirely of type 2 fibres. 4. The distribution of single motor units and their fibre types were determined for the caudal axons during development. In juvenile animals (toads of about 10 g body weight) the dorsal rind of tonic and slow fibres, together with the underlying homogeneous layer of type 2 fibres, were still present, but the rest of the muscle to the ventral surface consisted almost entirely of type 1 fibres. Caudal axons innervated the type 2 fibre layer at the dorsal surface as they do in mature animals. 5. The glutaeus in post-metamorphic toads (0.15 g body weight) had only a small number of tonic and slow-twitch fibres in the very dorsal layer of cells; the muscle was largely type 1.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1989

The probability of quantal secretion at release sites in different calcium concentrations in toad (Bufo marinus) muscle.

1. The number of quanta secreted from visualized release sites along terminal branches at toad (Bufo marinus) neuromuscular junctions in different extracellular concentrations of calcium ions. [Ca2+]o, and during facilitation was determined. Terminal branches were visualized by prior staining with the fluorescent dye, 3-3 diethyloxardicarbocyanine iodide (DiOC2(5)). 2. Increasing [Ca2+]o between 0.25 and 0.4 mM gave a similar proportional increase in the mean quantal content of the end-plate potential recorded with an extracellular electrode (me) at all sites along terminal branches. Thus the length constant for the experimental decline in me along terminal branches (the quantal length constant) remained constant with an increase in [Ca2+]o. The increase in m with [Ca2+]o followed a fourth power relation at both proximal and distal release sites. 3. The increase in me with [Ca2+]o was almost entirely due to an increase in the binomial probability for secretion, pe, which increased as the third to fourth power of [Ca2+]o. However, at higher [Ca2+]o there was an increasing tendency for the binomial parameter ne to increase. It is shown that when ne increases by about 1 there is very little change in pe, suggesting that the new release site recruited at high [Ca2+]o has a relatively low probability for secretion. 4. Test impulses gave a similar proportional increase in me following a conditioning impulse at all sites along terminal branches. The quantal length constant remained constant for both conditioning and test values of me. The increase in me for the test impulse increased linearly with an increase in me for the conditioning impulse at all release sites. 5. Facilitation of me declined exponentially with an increase in the test-conditioning interval. The time constant for this decline (30-40 ms) was similar at both proximal and distal release sites. Changes in facilitation of me were almost entirely due to changes in pe except at very short test-conditioning intervals of about 10 ms. At these intervals ne frequently increased by about 1 and there was very little change in pe. Again, this suggests that additional release sites recruited at short intervals have relatively low probability for secretion. 6. The results indicate that relatively low probability release sites exist in close juxtaposition to relatively high probability release sites which themselves decline in probability along the length of terminal branches.

Animals↗
PubMed1989

The probability of quantal secretion at release sites of different length in toad (Bufo marinus) muscle.

1. The evoked quantal secretion recorded with an extracellular microelectrode (me) at selected sites along motor terminal branches visualized with the fluorescent dye 3-3 diethyloxardicarbocyanine iodide (DiOC2(5)) was compared with the maximum length of the synaptic contact at these release sites reconstructed from serial sections examined with the electron microscope. In addition the relationship between the binomial probability of secretion at release sites (pe) and the length of the synaptic contact was determined in an extracellular calcium. [Ca2+]o, of 0.35 mM. 2. Three of the six terminal branches studied in this way showed a decline in synaptic contact length of release sites from near the point of nerve entry (proximal) to the end of the branch (distal). The remaining three branches showed an increase in synaptic contact length near their middle, and in each case this was associated with a Schwann cell nucleus: contact length then declined to the end of the branches. 3. Both me and pe increased linearly with an increase in the maximum length of the synaptic contact over a range from 0.4 to 4.0 microns. This occurred independently of how the synaptic contact length varied along the length of terminal branches. The value of pe increased by about 0.05 for each 1 micron increase in synaptic contact length in a [Ca2+]o of 0.35 mM. 4. The decrease in synaptic contact length along the proximal parts of terminal branches, in which this occurs, is mostly due to a decrease in the length of close opposition (less than 0.2 micron) between the nerve terminal membrane and the postsynaptic membrane: the decrease in more distal parts of branches is due to the progressive encroachment of Schwann cell processes between the presynaptic and postsynaptic membranes as well as a decrease in synaptic contact length.

Animals↗
PubMed1988

Migration of Schwann cells and axons into developing chick forelimb muscles following removal of either the neural tube or the neural crest.

A study has been made of the effects of neural crest and neural tube removal at the brachial level on the migration of Schwann cells and axons into the flexor digitorum profundus (fdp) and flexor carpi ulnaris (fcu) muscles of the avian forelimb. The identification of Schwann cells was based on the assumption that antibody HNK-1 uniquely labels these cells at the growing end of limb nerves. Myotubes and nerves were identified by using antibodies to myosin and to neurofilament protein, respectively. The removal of neural crest cells at stage 13 gave a complete Schwann cell-free embryo at the brachial level. Motor axons only grew to the base of the forelimb, forming a rudimentary plexus by stage 27, and failed to penetrate the limb. Removal of the neural tube at stage 13 did not prevent sensory axons from forming a plexus at the base of the limb; these axons subsequently developed into the brachialis longus inferior (bli n) and superior (bls n) nerves. By stage 27 the bli n had branched into the interosseus nerve (in n) and the medial-ulnar nerve (m-u n) trunks. However, unlike the result in control embryos, no nerves were detected amongst the developing fdp and fcu muscles, thus indicating that sensory axons do not grow into the muscles in the absence of motor axons. In contrast, Schwann cells were observed amongst the myotubes at the level of the in n and m-u nerve trunks. The present observations show that motor axons do not enter the limb bud and innervate limb muscles in the absence of Schwann cells. Furthermore, in the absence of motor axons (neural-tube-removed embryos) sensory axons still enter the limb (behind migrating Schwann cells) but fail to innervate developing muscles even though Schwann cells are present among the developing myotubes.

Animals↗
PubMed1988

The formation of topographical maps in developing rat gastrocnemius muscle during synapse elimination.

1. The rat lateral gastrocnemius muscle (LG) is a complex of four muscle compartments, each defined in terms of its unique innervation by a single primary nerve branch of the muscle nerve. A study has been made of the topographical distribution of motor units in the medial compartment of the LG (LGM) both before and after the loss of polyneuronal innervation that accompanies development. 2. Glycogen depletion methods showed that the distribution of single motor units depended on the rostro-caudal origins of their axons in the spinal cord: rostral axons possessed motor units almost exclusively confined to the medial half of the LGM; intermediate axons possessed motor units primarily in the intermediate and lateral part of the LGM; caudal axons possessed motor units that were not restricted to any particular part of the LGM. 3. Myosin ATPase staining showed that about 80% of the LGM consists of type II A fibres, whilst the remainder are type II B. Physiological determination of the contractile properties of motor units indicated two classes of units: those that were relatively fatigue resistant and did not show a sag property (like fast-twitch, fatigue-resistant fibres or FR) and those that were relatively fatigable and did show a sag property (like fast-twitch, fatigable fibres or FF). 4. Glycogen depletion was also used to determine the distribution of motor units in the LGM at 7 days post-natal, when most fibres still receive a polyneuronal innervation. The LGM primary nerve branch innervated a confined sub-volume of muscle fibres which is similar to the mature pattern. However, rostral axons possessed motor units that extended into the lateral half of the LGM, a position from which they are excluded in the adult. 5. These observations suggest that the axons of rostral and intermediate units form a topographical map within adult FR motor units (type II A fibres) in the LGM. The results suggest that competition between axon terminals for synaptic sites plays a role in the elimination of inappropriately positioned terminals and subsequent emergence of the topographical map.

Animals↗
PubMed1988

Quantal secretion at release sites of nerve terminals in toad (Bufo marinus) muscle during formation of topographical maps.

1. The number of quanta secreted from selected sites along terminal branches at suppressed synapses in the developing toad (Bufo marinus) gluteus muscle has been determined. The topographical projection from segmental nerves 8 and 9 to the ventral surface of this muscle matures slowly as toads develop in size from 12 to 40 g. Terminal branches of nerves 8 and 9 were visualized by prior staining with the fluorescent dye, 3-3-diethyloxardicarbocyanine iodide (DiOC2(5]. 2. The evoked quantal release recorded with an extracellular electrode (m(e) at different positions along the length of terminal branches at synaptic sites innervated either by nerve 8 (me,8) or nerve 9 (me,9) was determined in an external Ca2+ concentration, [Ca2+]o, of 0.35-0.45 mM. For over 90% of branches longer than 80 microns, me declined along exponential curves from a relatively large value at the proximal end of branches for both nerve 8 and nerve 9 terminals; the exponent for these exponential curves gave quantal length constants that varied from 26 to 80 microns (48 +/- 4 microns, mean +/- S.E.M.) depending on the length of the branch. 3. The evoked quantal release recorded with an intracellular electrode (m) at synaptic sites dually innervated by nerve 8 and nerve 9 was nearly always (greater than 90%) greater for nerve 8 terminals than for nerve 9 terminals. At singly innervated sites the value of m per 100 microns length of terminal declined approximately exponentially with an increase in total terminal length (length constant 400 microns). However, at dually innervated sites the value of m per 100 microns length of nerve 9 terminal was very low at all total terminal lengths compared with singly innervated sites; this indicates that nerve 9 terminals were suppressed at dually innervated sites. 4. At five dually innervated sites, seven out of nine terminal branches of nerve 8 showed an exponential decline in me,8 along their length, from a relatively large value near the proximal end of the branches (length constant 35 +/- 3 microns, mean +/- S.E.M.). In contrast, all the terminal branches of nerve 9 greater than 80 microns showed a uniformly low value of me,9 along their length. 5. It is suggested that the suppression of nerve 9 terminals at dually innervated sites is primarily due to a decrease in the probability of secretion of normally highly secreting release sites at the proximal end of terminal branches.

Action Potentials↗
PubMed1987

Growth of axons into developing muscles of the chick forelimb is preceded by cells that stain with Schwann cell antibodies.

A study has been made of the development of limb and muscle nerves in relation to the first appearance of Schwann cells in the flexor digitorum profundus (fdp) and flexor carpi ulnaris (fcu) muscles of the avian forelimb. Schwann cells were identified by immunofluorescent techniques with antibodies to the glycoprotein HNK-1. Myotubes and nerves were identified by using antibodies to myosin and to neurofilament, respectively. At stage 24/25 the brachialis longus inferior (Bli n) and superior (Bls n) nerve trunks within proximal regions of the forelimb were surrounded by Schwann cells. These cells extended in a column for a distance of approximately 100 microns beyond the growing ends of nerves. At stage 26 both interosseus nerve (in n) and the medial-ulnar nerve (m-u n) had formed from the Bli n; each of these branches was surrounded by Schwann cells, which again extended approximately 100 microns beyond the growing ends of the nerves. By stage 26/27 the fdp and fcu muscles were clearly delineated by groups of myotubes. No nerves were detected within these groups; however, Schwann cells were observed between the myotubes. At stage 27 axons had left the in n and m-u n and grown into the fdp and fcu muscles, respectively. These axons were surrounded by Schwann cells. The present observations show that Schwann cells are located ahead of the main limb and muscle nerves as they grow into the fdp and fcu muscles of the limb. It is possible that these Schwann cells play a role in guiding nerves to their correct muscles in the developing chick forelimb.

Animals↗
PubMed1987

Elimination of distributed synaptic acetylcholine receptor clusters on developing avian fast-twitch muscle fibres accompanies loss of polyneuronal innervation.

Changes in the distribution of large acetylcholine receptor clusters (AChR-Cs) on developing fast-twitch fibres of the chicken posterior latissimus dorsi (PLD) muscle have been studied during the period of loss of polyneuronal innervation using fluorescein-conjugated alpha-bungarotoxin. Embryonic muscles were ultrasonically dissociated into single fibre fragments and presumptive fast-twitch fibres were distinguished from the minority of slow-type fibres in the PLD by immunofluorescence using an antibody against slow-type myosin. Whereas mature PLD muscle fibres are focally innervated, at embryonic day 11 (E11) many fibre fragments from the PLD displayed two or more large (longer than 2 micron) AChR-Cs. Double labelling with anti-neurofilament antibody suggested that most of these AChR-Cs (82 +/- 2%) were associated with neuromuscular contacts. There was a progressive decline in the number of large (synaptic) AChR-Cs per 1000 micron of fibre, from 3.2 +/- 0.5 at E11 to 0.4 +/- 0.1 at E18. No further decline occurred between E18 and one week post-hatch. Primary generation muscle cells identified at E11 and E16 by tritiated thymidine labelling showed a decline in the number of large AChR-Cs per 1000 micron proportional to that seen in the fibre population as a whole, suggesting that distributed synaptic AChR-Cs are eliminated from individual fibres as they mature. When embryos were treated with d-tubocurarine starting at E6 the loss of distributed AChR-Cs from fast-type PLD fibres between E11 and E14 did not occur, suggesting that neuromuscular activity may play an important role in establishing the focal synaptic site AChR-C.

Animals↗
PubMed1987

Changes in the dimensions of release sites along terminal branches at amphibian neuromuscular synapses.

The probability of transmitter secretion from release sites declines along the length of most long terminal branches (greater than 78 micron) at toad (Bufo marinus) neuromuscular junctions; in contrast, few short terminal branches (less than 78 micron) show such a decline. The present study was carried out to see if any of the dimensions of release sites change along the length of terminal branches in a way that can be correlated with the decrease in secretion probability. The size of presynaptic release site structures was determined by examining serial transverse sections through entire terminal branches with the transmission electron microscope; the size of postsynaptic release site structures was determined by examining terminal gutters with the scanning electron microscope after the removal of terminal branches. Long terminal branches showed a significant decrease in the length of their synaptic contact and cross-sectional area (terminal size) with distance from the origin of the branch. In contrast, there was no significant difference in the length of close apposition (less than 0.2 micron) between the nerve terminal and postsynaptic muscle membrane; furthermore, neither the length of postsynaptic folds nor the frequency of the folds along the length of the terminal gutter changed. Short terminal branches showed no significant differences in the dimensions of either presynaptic or postsynaptic release site structures. The decline in the length of synaptic contacts whilst the length of close apposition remains relatively constant is due to the progressive encroachment of Schwann cell processes between presynaptic and postsynaptic membranes along the length of long terminal branches.

Animals↗
PubMed1987

Elimination of distributed acetylcholine receptor clusters from developing fast-twitch fibres in an avian muscle.

The development of the focal localization of large acetylcholine receptor clusters (AChR-Cs) on avian fast muscle fibres has been investigated in the triceps brachii pars humeralis (TH) muscle of the chick embryo. The mature TH muscle consists of both fast fibres, which usually receive a focal innervation at single synaptic sites, and slow fibres which receive a distributed innervation at multiple synaptic sites. Single fibre fragments dissociated from the embryonic muscle were typed using anti-myosin antibodies; fluorescently labelled alpha-bungarotoxin was used to identify large AChR-Cs which serve as synaptic markers. In contrast to the mature focal innervation, at embryonic day 11 (E11), many fast-type fibres in the TH muscle displayed large, distributed AChR-Cs (3.7 +/- 0.7 per 1000 microns fibre length; n = 6 embryos) like neighbouring slow-type fibres. By E16 distributed AChR-Cs were rare on fast type fibres (0.9 +/- 0.2 per 1000 microns fibre length). As it was possible that the frequency of fast fibres with distributed AChR-Cs declined simply as a consequence of the increase in number of secondary generation fibres, tritiated thymidine was injected at E7 in order to identify the primary generation fibres at E14. The great majority of fast fibres that were heavily labelled with thymidine at E14 appeared to possess a focal AChR-C. The results suggest that at E11 fast-type primary fibres in the TH muscle receive a distributed innervation very similar to neighbouring slow-type fibres; this subsequently evolves into the mature focal innervation following the elimination of synaptic sites between E11 and E14.

Adenosine Triphosphatases↗
PubMed1987

Retinal ganglion cell survival and neurite regeneration requirements: the change from Müller cell dependence to superior colliculi dependence during development.

A study has been made of the effects of Müller conditioned media or neonatal superior collicular extracts on the survival in dissociate culture of retinal ganglion cells (RGC) from differently aged rats. Embryonic and neonatal RGC were identified either by retrograde horseradish peroxidase (HRP) or Thy-1 antibody labelling techniques. Müller conditioned media supported the survival, over 24 h in culture, of 85% of the RGC plated from 17-day embryos (E17); in contrast, superior collicular extract only maintained 45% of these RGC. With further development there was a decline in the survival enhancing effects of the Müller conditioned media and an increase in the survival due to superior collicular extracts: by postnatal day 12 (P12), the survival of RGC had declined to 20% in the Müller media, but had increased to over 90% in the colliculus extract. This transition in the dependence of RGC from Müller cells to superior colliculi was examined with homogeneous cultures of RGC, obtained using cell sorting techniques. RGC in these cultures showed the same transition in dependence from Müller cells to superior colliculi, indicating that the survival-enhancing effects were not mediated by the other intrinsic cells of the retina. The results suggest that the survival of RGC is at first dependent on the intrinsic glia of the retina and only later, as development proceeds, on the targets of the RGC in the superior colliculus. The normal RGC death period in the rat extends from near birth to about 6 days postnatal. The question then arises as to the timing of trophic support from Müller glia and from neurones in the tectum in relation to the duration of the normal RGC death period. This has been examined in the present work.

Animals↗