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F Haun

Publications and source records attributed to F Haun.

18 recordsLinked to original sources
PubMed1992

Rescue of both rapidly and slowly degenerating neurons in the dorsal lateral geniculate nucleus of adult rats by a cortically derived neuron survival factor.

We investigated the death of dorsal lateral geniculate nucleus (dLGN) neurons after lesions to the visual cortex of adult rats and the effects of supplying target-derived neurotrophic molecules to the lesion cavity. The neurotrophic factor is retrieved from cocultures of the embryonic primordia of the geniculocortical pathway and its survival promoting properties for different populations of dLGN neurons (based on their time of origin) have been documented in previous studies of neonatal rats with occipital cortex lesions. In the present study, rats were exposed to [3H]thymidine on E14 or E15/16 to label either earlier or later generated dLGN neurons. When animals were at least 45 days old we made discrete lesions to the principal projection zones in area 17 of these two dLGN populations. Counts of surviving labeled cells show a relatively rapid death of E15/16 dLGN neurons in control animals, with a maximal loss by 2 weeks postlesion. The death of E14 dLGN neurons is more protracted, with a maximal loss by 2 months postlesion. A 2-week infusion of the CM fraction rescues the majority of the neurons that would otherwise die in both populations compared to the controls which receive a similarly prepared fraction of unconditioned medium. Moreover, this CM fraction can sustain E14-generated dLGN neurons up to 6 weeks after the neurotrophic factor(s) is no longer being supplied exogenously. Thus the rescue of axotomized adult dLGN neurons appears to be permanent, at least for the early generated population. These findings are consistent with the idea that target-derived molecules have a role in the survival of mature neurons, as they are known to have for developing neurons.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Habenula and thalamus cell transplants mediate different specific patterns of innervation in the interpeduncular nucleus.

Innervation of specific peptidergic and cholinergic compartments of the interpeduncular nucleus (IPN) was investigated using embryonic cell suspension transplants immunoreactive for substance P (SP) and ChAT. In both neonatal and adult host rats, the IPN was first denervated of its normal SP and cholinergic input from the medial habenula by bilateral lesions of the fasciculi retroflexi (FR). In adult hosts, transplants of embryonic habenular cells placed near the denervated IPN mediated a return of the normal pattern of SP staining restricted to habenula-target subnuclei, plus an increase in staining intensity of SP cells intrinsic to the IPN. There was no recovery of ChAT staining. A similar pattern of SP staining resulted following habenular transplants into neonatal hosts, but in addition there was a partial recovery of normal ChAT staining in cholinergic subnuclei and anomalous ChAT staining in normally peptidergic subnuclei. Control transplants of embryonic thalamus cells placed into adult hosts produced a surprising pattern of ChAT staining in the IPN identical to that seen with habenula transplants placed into neonatal hosts; the adult IPN was thus able to support reinnervation mediated by an aberrant cholinergic source while being refractory to its normal habenular cholinergic afferents. This pattern of results implies regulation by the IPN of habenular SP and cholinergic innervation, and some interaction between the maturing normal cholinergic afferents and their targets that is missing when these afferent sources are abnormal.

Animals↗
PubMed1992

Habenula and thalamus cell transplants restore normal sleep behaviors disrupted by denervation of the interpeduncular nucleus.

The preceding companion study (Eckenrode et al., 1992) showed that cell suspension transplants of fetal habenula cells placed near the interpeduncular nucleus (IPN) following lesions of the fasciculus retroflexus (FR) restore the normal pattern of substance P (SP) staining in habenular target subnuclei of the IPN in both perinatal and adult hosts, and restore ChAT staining in the IPN of perinatal hosts. Similarly placed transplants of fetal thalamus cells only restore ChAT staining in the IPN of adult hosts. In this study, we examined the functional significance of these restored staining patterns. We used a behavioral measure of the integrity of REM-stage and non-REM-stage sleep, the "flower pot" test, and assayed (1) normal adult rats, (2) FR-lesioned control animals (neonatal or adult operates), (3) animals receiving FR lesions and transplants of fetal habenula cells (perinatal or adult hosts), and (4) animals receiving FR lesions and transplants of fetal thalamus cells (adult hosts). FR lesions decrease markedly the muscle atonia component of REM sleep and reduce duration of sleep episodes. Transplants that restore SP staining in the IPN (habenular transplants into either perinatal or adult lesion hosts) restore normal frequency of REM atonia; transplants that restore ChAT staining (habenular transplants into perinatal hosts or thalamic transplants into adult hosts) restore normal duration of sleep episodes. The number of SP-immunoreactive cells in the transplants predicts recovery of REM atonia, and the number of ChAT cells in habenular (but not thalamic) transplants predicts restoration of sleep duration.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Different populations of dorsal lateral geniculate nucleus neurons have concentration-specific requirements for a cortically derived neuron survival factor.

A macromolecular fraction of conditioned culture medium (CM) derived from explant cocultures of embryonic rat posterior cortex and caudal thalamus is able to support the survival of neurons in the dorsal lateral geniculate nucleus (dLGN) of newborn rats following ablation of dLGN cortical target areas. In the present study we tested whether the survival-promoting activity of this target-derived neurotrophic agent was concentration dependent and whether different subpopulations of dLGN neurons were equally responsive. With the starting concentration of the CM fraction designated X, increasing concentration results in a progressive falloff in trophic activity so that at 200X overall dLGN survival is similar to that seen in unconditioned medium (UM) controls. In contrast, diluting the fraction produces an increase in activity until maximal survival is achieved at 0.2X. Further dilutions result in a decline in trophic activity until control values are reached at 0.001X. Two populations of neurons within the dLGN, defined by their time of origin, respond in a specific manner to the different concentrations. Neurons generated during the early stages of neurogenesis (E14) have maximal survival (25.8%) at 0.05X, whereas those neurons generated later (E15/16) are maximally supported (30.7% survival) at 10X, a 200-fold difference in concentration. While it is possible that separate neurotrophic and neurotoxic molecules exist for each of these populations of dLGN neurons, the most parsimonious interpretation of the data is that a single cortically derived neurotrophic factor exists whose production is strictly controlled during development to achieve maximal effect on different populations of thalamic neurons that may be functionally distinct.

Animals↗
PubMed1989

Neurotrophic and behavioral effects of occipital cortex transplants in newborn rats.

Cell suspensions of embryonic occipital cortex were transplanted into newborn rats with large unilateral visual cortex lesions. When the animals were adults, they were tested on a difficult visual discrimination, and subsequently their brains were analyzed for possible neurotrophic effects of the transplants on nonvisual cortical areas which normally form connections with the occipital cortex. Behaviorally, animals with lesions and transplants learn to discriminate between columns and rows of squares at a rate which is identical to normal rats while animals with lesions and no transplants are impaired. Volume and cell-density measures show that the transplants also rescue neurons in cortical area 8 that would normally degenerate following the cortical lesion. No such neurotrophic effect of the transplants is found in cortical area 24 or area 17 contralateral to the lesion. In rats with lesions and no transplants, there is a significant correlation between the amount of area 8 remaining after the lesion and trials to criterion on the columns-rows discrimination, a relationship that does not exist in transplant animals because of their normal learning curve and the consistent sparing of area 8. Injections of HRP into the visual cortex contralateral to the lesion result in variable numbers of labeled cells within the transplant. However, there is no consistent relationship between the number of transplant cells which project to the opposite hemisphere and learning of the discrimination. It is suggested that the learning deficit following the lesion is largely attentional and that the sparing of cortical area 8 (which in rats may include the analog of the frontal eye fields present in the primate cortex) contributes to the sparing of function.

Animals↗
PubMed1987

Diffusible proteins prolong survival of dorsal lateral geniculate neurons following occipital cortex lesions in newborn rats.

Removal of the occipital cortex in newborn rats results in the rapid and nearly complete degeneration of the dorsal lateral geniculate nucleus (dLGN) in 5 days. In previous studies we have shown that transplants of embryonic posterior cortex neurons, which are allowed to develop in culture for 5 days prior to transplantation into the site of the lesion, prolong the survival of a particular population of host dLGN neurons for an additional week. In this study we tested the possibility that the transplant cells synthesize diffusible proteins which are responsible for this neurotrophic effect. Culture medium conditioned by explants of embryonic occipital cortex and diencephalon was concentrated by vacuum dialysis or ultrafiltration through membranes with at least a 10-kDa cut-off. This concentrated medium was loaded into polyacrylamide or sodium alginate gels which were then implanted into the cavity of the lesion. Five days after implantation, the alginate-conditioned-medium implants result in a 3-fold increase in dLGN survival compared to unconditioned medium controls, while a two-fold increase in survival of the nucleus is found with the polyacrylamide-conditioned-medium implants. Proteolysis of the conditioned medium eliminates all neurotrophic activity. The results suggest that the death of dLGN neurons following the cortical lesion is due to the loss of diffusible proteinaceous neurotrophic factors--factors that may operate during normal in vivo development of the geniculocortical pathway.

Animals↗
PubMed1987

Specific neurotrophic interactions between cortical and subcortical visual structures in developing rat: in vivo studies.

The specificity of trophic interactions in the rat visual system is investigated in vivo by using a combination of tissue culture and CNS transplantation methods. In a companion paper (Repka and Cunningham: '87) we showed that explants of embryonic day 14 (E14) occipital cortex are biased to contain different cortical cell populations depending on whether the explants develop in culture with diencephalon or with optic tectum. In this study we transplanted these precultured cortical explants into the cavity created by a lesion of the occipital cortex in newborn rats and then measured the neuron-occupied volume and the numbers of thymidine-labeled cells in the surviving ipsilateral dorsal lateral geniculate nucleus (dLGN) of the host rats. The results were compared to animals with lesions but no transplants, animals with transplants of E14 cortical tissue that had not been precultured, and animals with cerebellar transplants that had been similarly precultured either with other cerebellar tissue or with diencephalon. At 5 days postlesion, both the largest dLGN volume and the greatest number of labeled dLGN neurons survive in animals with cortical transplants precultured with diencephalon or other cortex. The surviving dLGN neurons that are rescued by these transplants are generated on E15 or E16, a period that corresponds to the latter part of geniculate neurogenesis. Relatively few cells generated on E14 survive in any group of animals. Furthermore, animals with all types of cortical transplants have significantly larger volumes of surviving dLGN than animals with either lesions only or cerebellar transplants.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1978

Letter identification as a function of type of perceptual limitation and type of attribute.

It is argued that the distribution of errors in letter identification depends on two factors: (a) whether the set of letters is defined by features that exist or do not exist or by dimensions that exist at some positive value, and (b) whether errors are produced by process limitation in which the letter patterns are distorted or by state limitation in which there is inadequate energy. A specific hypothesis tested was that error distributions reflect the attribute structure under both types of limitation if dimensions define the letter set, but only under a process limitation if features define the letter set. Under a state limitation, feature set errors are primarily produced by a loss of features, so that a letter with more features is called a letter with fewer features more often than conversely. An experiment completely validated the hypothesis under test. In addition, the relative discriminabilities of two dimensions defining a dimension set of letters was reversed from state to process limitation. Thus the attribute structure derived from error distributions is not invariant across types of perceptual limitation, nor are distances between letter pairs always symmetric.

Discrimination, Psychological↗