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D R Riddle

Publications and source records attributed to D R Riddle.

At least 19 recordsLinked to original sources
PubMed2004

Regulation of cytochrome oxidase activity in the rat forebrain throughout adulthood.

Measures of metabolic activity can provide useful indices of the effects of aging on neural function, since sustained changes in neural activity alter metabolic demand and the activity of metabolic enzymes. Previous reports of effects of aging on key enzymes for oxidative metabolism are mixed, however, with some reports that activity declines in the aging brain and others that activity remains stable or increases. We used high-resolution, quantitative histochemistry to test whether cytochrome oxidase (CO) activity changes in the forebrain during adulthood and senescence, measuring activity in each layer of the hippocampus and several cerebral cortical areas. In most forebrain regions, average cytochrome oxidase activity was slightly higher in middle-aged than in young adult rats but did not differ between middle-aged and old rats. Thus, there was no significant change in cytochrome oxidase activity with senescence. Additional analyses indicated that cytochrome oxidase activity is regulated regionally in the brain, as well as focally, and that differences in regional regulation may contribute to variation in CO activity among individuals, which was greater in young and old rats than in middle-aged animals.

Age Factors↗
PubMed2001

Laminar variation in neuronal viability and trophic dependence in neocortical slices.

Organotypic slices are used frequently in studies of central nervous system development and function because they provide excellent experimental access with significant preservation of cellular context and relationships. Within a slice, however, a variety of factors may cause individual classes of neurons to respond differently to the culture environment. Differences in deafferentation, cellular maturation, trophic dependence and ongoing naturally occurring cell death may produce changes in the neuronal population that are transparent to the experimenter but that could affect experimental results significantly. In this study, we examined the distribution and prevalence of cell death among neurons in each cortical layer in organotypic slices. In addition, we assessed the ability of several neurotrophic factors to ameliorate neuronal death in each cortical layer. Within the first 24 hr in culture, there was striking laminar variation in the extent of neuronal death in culture, which could not be accounted for by the pattern of programmed cell death in vivo. In addition, neurons in the six layers of the neocortex differed in the degree to which they could be rescued by neurotrophic factors. These data suggest that differential neuronal death and rescue are important considerations in studies utilizing organotypic slices and may represent particularly confounding variables in studies of effects of trophic factors in such preparations.

Animals↗
PubMed2001

Effects of age and insulin-like growth factor-1 on neuron and synapse numbers in area CA3 of hippocampus.

Age-related effects associated with the hippocampus include declines in numbers of neurons and synapses in the dentate gyrus and area CA1, and decreased cognitive ability as assessed with the Morris water maze. The present study quantified both neuron and synapse number in the same tissue block of area CA3 of the hippocampus. No investigations of both density of neurons and synapses together in area CA3 of hippocampus have been performed previously, despite its importance as the terminal field of dentate gyrus mossy fibers, the second synapse in the trisynaptic circuit in the hippocampus. Numerical density of neurons and synapses were assessed in 4-, 18-, and 29-month-old rats receiving infusions of saline into the lateral ventricle and in 29-month-old rats receiving infusions of insulin-like growth factor-1 (IGF-1). Numerical density of neurons of the stratum pyramidale of CA3 of hippocampus remained constant across the life span as did the numerical density of synapses in stratum lucidum of area CA3. Despite the reported role of IGF-1 in synaptogenesis and improvements in behavior with age, ventricular infusion of this growth factor did not affect the numerical density of neurons or synapses in 29-month-old rats when compared to saline-infused old rats. Further, reported effects of IGF-1 on adult neurogenesis in the dentate gyrus are not reflected in an IGF-1-related increase in synapse density in this region.

Aging↗
PubMed2001

Intracerebroventricular infusion of insulin-like growth factor-I ameliorates the age-related decline in hippocampal neurogenesis.

The dentate gyrus of the hippocampus is one of few regions in the adult mammalian brain characterized by ongoing neurogenesis. Significantly, recent studies indicate that the rate of neurogenesis in the hippocampus declines with age, perhaps contributing to age-related cognitive changes. Although a variety of factors may influence the addition of new neurons in the adult dentate gyrus, the mechanisms responsible for the age-related reduction remain to be established. Insulin-like growth factor-I (IGF-I) is one promising candidate to regulate neurogenesis in the adult and aging brain since it influences neuronal production during development and since, like the rate of neurogenesis, it decreases with age. In the current study, we used bromodeoxyuridine labeling and multilabel immunofluorescence to assess age-related changes in neuronal production in the dentate gyrus of adult Brown Norway x Fischer 344 rats. In addition, we investigated the relationship between changes in neurogenesis and the age-dependent reduction in IGF-I by evaluating the effect of i.c.v. infusion of IGF-I on neurogenesis in the senescent dentate gyrus. The analyses revealed an age-dependent reduction in the number of newly generated cells in the adult dentate subgranular proliferative zone and, in addition, a 60% reduction in the differentiation of newborn cells into neurons. Restoration of IGF-I levels in senescent rats significantly restored neurogenesis through an approximately three-fold increase in neuronal production. The results of this study suggest that IGF-I may be an important regulator of neurogenesis in the adult and aging hippocampus and that an age-related decline in IGF-I-dependent neurogenesis could contribute to age-related cognitive changes.

Aging↗
PubMed2000

Insulin-like growth factor I stimulates dendritic growth in primary somatosensory cortex.

The temporal and spatial distributions of several growth factors suggest roles in the regulation of neuronal differentiation in the neocortex. Among such growth factors, the insulin-like growth factors (IGF-I and -II) are of particular interest because they are available to neurons from multiple sources under independent control. IGF-I is produced by many neurons throughout the brain and also by cells in the cerebral vasculature. IGF-II is found at high levels in the CSF, and both IGF-I and IGF-II cross the blood-brain barrier. Thus, the IGFs may act as both paracrine and endocrine regulators of neuronal development. As an initial step toward understanding the influence of IGFs in the developing cerebral cortex, the present study examined the effects of IGF-I and of the neurotrophins brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) on the dendritic complexity of layer 2 pyramidal neurons. The results demonstrate that IGF-I increased the branching and total extent of both apical and basal dendrites of pyramidal cells in organotypic slices of rat primary somatosensory cortex. BDNF and NT-3 also enhanced dendritic development, but the two neurotrophins increased the extent of only basal, not apical, dendrites and promoted greater elongation than was seen after IGF-I treatment. These results provide direct evidence that IGF-I can regulate the dendritic elaboration of cortical neurons and indicate that endogenous IGFs may influence dendritic differentiation and the formation of cortical connections. In addition, IGF-dependent regulation of dendritic structure may represent a link between age-related declines in IGFs and cognitive deficits seen in senescence.

Animals↗
PubMed1997

Focal delivery of neurotrophins into the central nervous system using fluorescent latex microspheres.

A new technique for in vivo and in vitro delivery of neurotrophins is described. The method is based upon the ability of certain fluorescent latex microspheres to adsorb large quantities of neurotrophin and then release the factor for at least three to four days. Injection of such neurotrophin-coated microspheres in vivo provides focal delivery of neurotrophins to distinct populations of neurons. The fluorescence of the microspheres accurately identifies the region of neurotrophin treatment in vivo; two independent methods indicate that microsphere-born proteins do not diffuse significantly beyond the site of injection. In addition to providing focal delivery and labeling of the site of application, labeled microspheres are retrogradely transported by neurons; thus, neurons whose distant terminals are exposed to neurotrophin can be identified and analyzed. This approach provides a powerful method for the introduction of neuroactive proteins into defined and localized regions of the central nervous system.

Animals↗
PubMed1996

Is neural development Darwinian?

Gradually, and without much debate, the idea that the developing nervous system is in some sense darwinian has become one of the canons of neurobiology. In fact, there is little evidence to support this idea.

Age Distribution↗
PubMed1995

NT-4-mediated rescue of lateral geniculate neurons from effects of monocular deprivation.

Altering the balance of activity between the two eyes during the critical period for visual-system development profoundly affects competitive interactions among neurons in the lateral geniculate nucleus and primary visual cortex. Neurons in the lateral geniculate nucleus that are deprived of activity by closing or silencing one eye atrophy as a result of competition with non-deprived neurons for some critical factor(s) presumed to be present in the cortex. Based on their actions in the developing visual system, neurotrophins are attractive candidates for such factors. We tested whether neurotrophins mediate intracortical competition of afferents from the lateral geniculate nucleus by using monocular deprivation and a new method for highly localized, in vivo delivery of neurotrophins. This method allowed unambiguous identification of neurons that were exposed to neurotrophin. Here we report that only one neurotrophin, the TrkB ligand NT-4, rescued neurons in the lateral geniculate nucleus from the dystrophic effects of monocular deprivation.

Animals↗
PubMed1995

Individual variation and lateral asymmetry of the rat primary somatosensory cortex.

We have evaluated the interindividual variability and lateral symmetry of a major cortical area by comparing the primary somatosensory cortex (S1) of adult rats. Our choice of the rat was dictated by the accuracy with which one can measure S1 and its component representations in the rodent brain; the importance of such measurements lies in understanding the rules that govern the allocation of cortical space and, ultimately, the consequences of differential allocation for behavior. With respect to interindividual differences, the major somatic representations in S1 are surprisingly variable in size. The area of the whiskerpad representation, for example, ranged from 3.72 to 6.84 mm2 in a sample of 53 rats; other components of S1 showed comparable differences among animals. With respect to lateral symmetry, the average area of each major representation was similar for the right and left hemispheres; thus, we found no consistent bias in the size of S1 or its elements in the sample as a whole. Within individual animals, however, the sizes of the major somatic representations were often quite different in the two hemispheres. The magnitude of the lateral differences averaged 7.9 +/- 0.8% (mean +/- SEM) for the whisker pad representation, 11.6 +/- 1.3% for the upper lip, 15.4 +/- 1.6% for the furry buccal pad, 13.9 +/- 1.4% for the lower jaw, and 13.3 +/- 1.2% for the forepaw. These results show that the amount of cortical space allocated to corresponding functions in individual rats--or in the two hemispheres of a particular rat--are often different. Such variations are likely to be reflected in somatosensory performance.

Animals↗
PubMed1994

Neural activity and the development of the somatic sensory system.

Present thinking about the role of neural activity in the developing brain is based largely upon observations in the visual system. Attempts to generalize these findings in the somatic sensory system, however, have yielded perplexing results. Unlike the visual system, recent evidence suggests that activity plays a relatively minor role in establishing structural patterns in the primary somatic sensory cortex. Activity levels in the primary somatic sensory cortex are nonetheless highest in those regions that grow most during postnatal development, implying that activity promotes differential cortical growth.

Animals↗
PubMed1993

Morphometric and immunocytochemical assessment of fungiform taste buds after interruption of the chorda-lingual nerve.

Unilateral interruption of the chorda-lingual nerve led to a loss of most epithelial axons and to the deterioration of fungiform taste buds in the anterior portion of the tongue of albino rats, mongolian gerbils, and golden hamsters. By three weeks after surgery the following percentages of fungiform taste buds had completely disappeared: 71% in gerbils, 28% in rats, and 26% in hamsters. Residual taste buds were classified into two groups: atrophic taste buds and taste bud remnants. Atrophic taste buds were smaller than normal and typically had no visible taste pore, although they retained the characteristic oval shape of a taste bud and numerous elongated cells. Taste bud remnants were non-oval fragments of taste buds with few elongated cells. Specific markers for elongated taste cells (monoclonal antibodies to keratin 19) confirmed that atrophic taste buds, as well as some taste bud remnants, had elongated taste cells. By 180 days after chorda-lingual nerve transection, 44% of rat fungiform taste buds had disappeared; morphometric analysis of the 311 residual taste buds established that 241 atrophic taste buds and 69 taste bud remnants were, respectively, 50% and 75% smaller than the average volume of 480 normal taste buds. The aggregate loss of gustatory tissue, calculated from the shrinkage of residual taste buds and the volume lost by the outright disappearance of many taste buds, was 88% for gerbils, 72% for rats, and 65% for hamsters. Evaluation in gerbils of the co-occurrence of taste buds and axons suggests residual taste buds were neurotrophically supported. Every gerbil fungiform papilla that lacked axons lacked a taste bud.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Lectin identification of olfactory receptor neuron subclasses with segregated central projections.

Our previous studies have demonstrated that the primary olfactory projection in rainbow trout is organized nontopographically; the pattern of termination of olfactory axons in the olfactory bulb is unrelated to the distribution of their cell bodies in the olfactory mucosa. In the present research we have further characterized the organization of this projection by examining the lectin-binding properties of olfactory receptor neurons. The results indicate that in trout, as in mammals, populations of olfactory receptor neurons differ significantly from one another in their carbohydrate "signatures." We have identified subsets of olfactory receptor neurons, specified by unique lectin-binding properties, that are widely distributed and intermingled with the other receptor neurons in the olfactory mucosa and nerve, but that segregate as they enter the olfactory bulb and project to restricted regions of the glomerular layer. This pattern of terminations is bilaterally symmetrical, is remarkably consistent across individuals, and reappears when the primary olfactory projection is reconstituted following transection of the olfactory nerve. As revealed by the carbohydrates on subpopulations of receptor neurons, there is substantial order in the nontopographic projection of olfactory receptor neurons to the olfactory bulb. The functional significance of this organization and the means by which it develops and is maintained remain under investigation.

Animals↗
PubMed1993

Differential metabolic and electrical activity in the somatic sensory cortex of juvenile and adult rats.

We have examined relative levels of metabolic and electrical activity across layer IV in the primary somatic sensory cortex (S1) of the rat in relation to regions of differential postnatal cortical growth. Each of several indices used--mitochondrial enzyme histochemistry, microvessel density, Na+/K+ pump activity, action potential frequency, and deoxyglucose uptake--indicate regional variations of metabolic and electrical activity in this part of the brain in both juvenile (1-week-old) and adult (10-12-week-old) animals. At both ages, areas of the somatic sensory map related to special sensors such as whiskers and digital pads showed evidence of the most intense activity. Thus, mitochondrial enzyme staining, blood vessel density, and Na+/K+ ATPase activity were all greatest in the barrels and barrel-like structures within S1, and least in the adjacent interbarrel cortex and the cortex surrounding S1. Multiunit recordings in and around the posteromedial barrel subfield of anesthetized animals also showed that the average ratio of evoked to spontaneous activity was greater in barrels than in the surrounding, metabolically less active cortex. Furthermore, autoradiograms of labeled deoxyglucose accumulation in awake behaving animals indicated systematic differences in neural activity across S1 barrels and barrel-like structures showed more deoxyglucose accumulation than interbarrel, nonbarrel, or peri-S1 cortex. These regional differences in neural activity correspond to regional differences in neocortical growth (Riddle et al., 1992). The correlation of greater electrical activity, increased metabolism, and enhanced cortical growth during postnatal maturation suggests that neural activity foments the elaboration of circuitry in the developing brain.

Action Potentials↗
PubMed1992

Immunocytochemical identification of primary olfactory afferents in rainbow trout.

We have used a combination of techniques to analyze the primary olfactory projection in trout: anterograde tract tracing with horseradish peroxidase (HRP) and immunocytochemistry with antisera to olfactory marker protein (OMP) and to keyhole limpet hemocyanin (KLH). HRP labeling and the OMP antiserum revealed a subset of ciliated receptor neurons with a wide dendrite that lacked the protruding knob found on other receptor neurons. The organization of the primary olfactory axons was clearly revealed by antisera to KLH, which reacted with no other neurons. When visualized with anti-KLH, fascicles of olfactory axons penetrated the basal lamina of the olfactory rosette at scattered sites and converged to form the olfactory nerve. Fascicles within the olfactory nerve traveled parallel to the long axis of the nerve until resorted by extensive intermixing as they entered the olfactory bulb. Within the olfactory bulb, most axons terminated in nine discrete terminal fields in the glomerular layer; however, a few olfactory nerve axons projected into the ventral medial telencephalon. Fascicles supplying each terminal field in the glomerular layer followed distinctive trajectories within the olfactory nerve layer. Axons ending in two terminal fields made brush-like terminations rather than the glomerular terminations characteristic of the remaining seven fields. After unilateral olfactory nerve transection, returning olfactory axons reestablished the normal pattern of terminal fields within 14 weeks. It is likely that the organization of afferents in the trout olfactory bulb is similarly well regulated during normal receptor cell replacement.

Animals↗
PubMed1992

Receptor cell regeneration and connectivity in olfaction and taste.

The capacity of adult mammalian gustatory and olfactory receptor cells to regenerate and make synaptic reconnections provides examples that may be useful in initiating replacement of other kinds of sensory receptor cells. The sensory code for taste quality may not be degraded by taste receptor cell turnover because axons probably recouple to the appropriate type of new receptor cell by axon-receptor cell affinity. Experiments on the development and regeneration of taste receptor cells suggest that they regenerate and turn over by recapitulating the late but not the early steps in taste bud development. To evaluate the replacement of vertebrate olfactory receptors, we began by characterizing the spatial pattern of primary olfactory projections in rainbow trout. Contiguous clusters of HRP-labeled olfactory receptor neurons (ORN) make highly divergent projections to the olfactory bulb. Retrograde transport of fluorescent latex beads revealed that a given restricted site in the glomerular layer received axons from ORNs widely scattered in the epithelium. Hence, ORN axons do not form point-to-point or regional topographic maps. Rather, the olfactory epithelial sheet makes a plane-to-point or holographic-like projection, since any given point in the glomerular layer receives information from the entire olfactory epithelial plane. Receptor cells that reacted with the lectin pokeweed agglutinin were highly dispersed in the olfactory epithelium with axons widely scattered in the olfactory nerve. Yet, as a consequence of the extensive reaggregation of axons at the nerve-bulb interface, the lectin-positive axons fasciculated and converged into a subregion of the glomerular layer.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Iterated patterns of brain circuitry (or how the cortex gets its spots)

The prominence of repeating patterns of circuitry in the mammalian brain has led to the general view that iterated modular units reflect a fundamental principle of cortical function. Here we argue that these intriguing patterns arise not because the functional organization of the brain demands them, but as an incidental consequence of the rules of synapse formation.

Animals↗