Biomedical subjects

Susan L Wearne

Publications and source records attributed to Susan L Wearne.

6 recordsLinked to original sources

PubMed2006

Precerebellar hindbrain neurons encoding eye velocity during vestibular and optokinetic behavior in the goldfish.

Elucidating the causal role of head and eye movement signaling during cerebellar-dependent oculomotor behavior and plasticity is contingent on knowledge of precerebellar structure and function. To address this question, single-unit extracellular recordings were made from hindbrain Area II neurons that provide a major mossy fiber projection to the goldfish vestibulolateral cerebellum. During spontaneous behavior, Area II neurons exhibited minimal eye position and saccadic sensitivity. Sinusoidal visual and vestibular stimulation over a broad frequency range (0.1-4.0 Hz) demonstrated that firing rate mirrored the amplitude and phase of eye or head velocity, respectively. Table frequencies >1.0 Hz resulted in decreased firing rate relative to eye velocity gain, while phase was unchanged. During visual steps, neuronal discharge paralleled eye velocity latency (approximately 90 ms) and matched both the build-up and the time course of the decay (approximately 19 s) in eye velocity storage. Latency of neuronal discharge to table steps (40 ms) was significantly longer than for eye movement (17 ms), but firing rate rose faster than eye velocity to steady-state levels. The velocity sensitivity of Area II neurons was shown to equal (+/- 10%) the sum of eye- and head-velocity firing rates as has been observed in cerebellar Purkinje cells. These results demonstrate that Area II neuronal firing closely emulates oculomotor performance. Conjoint signaling of head and eye velocity together with the termination pattern of each Area II neuron in the vestibulolateral lobe presents a unique eye-velocity brain stem-cerebellar pathway, eliminating the conceptual requirement of motor error signaling.

Animals↗

PubMed2006

Estrogen alters spine number and morphology in prefrontal cortex of aged female rhesus monkeys.

Long-term cyclic treatment with 17beta-estradiol reverses age-related impairment in ovariectomized rhesus monkeys on a test of cognitive function mediated by the prefrontal cortex (PFC). Here, we examined potential neurobiological substrates of this effect using intracellular loading and morphometric analyses to test the possibility that the cognitive benefits of hormone treatment are associated with structural plasticity in layer III pyramidal cells in PFC area 46. 17beta-Estradiol did not affect several parameters such as total dendritic length and branching. In contrast, 17beta-estradiol administration increased apical and basal dendritic spine density, and induced a shift toward smaller spines, a response linked to increased spine motility, NMDA receptor-mediated activity, and learning. These results document that, although the aged primate PFC is vulnerable in the absence of factors such as circulating estrogens, it remains responsive to long-term cyclic 17beta-estradiol treatment, and that increased dendritic spine density and altered spine morphology may contribute to the cognitive benefits of such treatment.

Aging↗

PubMed2004

Automated algorithms for multiscale morphometry of neuronal dendrites.

We describe the synthesis of automated neuron branching morphology and spine detection algorithms to provide multiscale three-dimensional morphological analysis of neurons. The resulting software is applied to the analysis of a high-resolution (0.098 microm x 0.098 microm x 0.081 microm) image of an entire pyramidal neuron from layer III of the superior temporal cortex in rhesus macaque monkey. The approach provides a highly automated, complete morphological analysis of the entire neuron; each dendritic branch segment is characterized by several parameters, including branch order, length, and radius as a function of distance along the branch, as well as by the locations, lengths, shape classification (e.g., mushroom, stubby, thin), and density distribution of spines on the branch. Results for this automated analysis are compared to published results obtained by other computer-assisted manual means.

Algorithms↗

PubMed2003

Automated reconstruction of three-dimensional neuronal morphology from laser scanning microscopy images.

Experimental and theoretical studies demonstrate that both global dendritic branching topology and fine spine geometry are crucial determinants of neuronal function, its plasticity and pathology. Importantly, simulation studies indicate that the interaction between local and global morphologic properties is pivotal in determining dendritic information processing and the induction of synapse-specific plasticity. The ability to reconstruct and quantify dendritic processes at high resolution is therefore an essential prerequisite to understanding the structural determinants of neuronal function. Existing methods of digitizing 3D neuronal structure use interactive manual computer tracing from 2D microscopy images. This method is time-consuming, subjective and lacks precision. In particular, fine details of dendritic varicosities, continuous dendritic taper, and spine morphology cannot be captured by these systems. We describe a technique for automated reconstruction of 3D neuronal morphology from multiple stacks of tiled confocal and multiphoton laser scanning microscopy (CLSM and MPLSM) images. The system is capable of representing both global and local structural variations, including gross dendritic branching topology, dendritic varicosities, and fine spine morphology with sufficient resolution for accurate 3D morphometric analyses and realistic biophysical compartment modeling. Our system provides a much needed tool for automated digitization and reconstruction of 3D neuronal morphology that reliably captures detail on spatial scales spanning several orders of magnitude, that avoids the subjective errors that arise during manual tracing with existing digitization systems, and that runs on a standard desktop workstation.

Animals↗

PubMed2003

Age-related dendritic and spine changes in corticocortically projecting neurons in macaque monkeys.

Alterations in neuronal morphology occur in primate cerebral cortex during normal aging, vary depending on the neuronal type, region and cortical layer, and have been related to memory and cognitive impairment. We analyzed how such changes affect a specific subpopulation of cortical neurons forming long corticocortical projections from the superior temporal cortex to prefrontal area 46. These neurons were identified by retrograde transport in young and old macaque monkeys. Dendritic arbors of retrogradely labeled neurons were visualized in brain slices by intracellular injection of Lucifer Yellow, and reconstructed three-dimensionally using computer-assisted morphometry. Total dendritic length, numbers of segments, numbers of spines, and spine density were analyzed in layer III pyramidal neurons forming the projection considered. Sholl analysis was used to determine potential age-related changes in dendritic complexity. We observed statistically significant age-related decreases in spine numbers and density on both apical and basal dendritic arbors in these projection neurons. On apical dendrites, changes in spine numbers occurred mainly on the proximal dendrites but spine density decreased uniformly among the different branch orders. On basal dendrites, spine numbers and density decreased preferentially on distal branches. Regressive dendritic changes were observed only in one particular portion of the apical dendrites, with the general dendritic morphology and extent otherwise unaffected by aging. In view of the fact that there is no neuronal loss in neocortex and hippocampus in old macaque monkeys, it is possible that the memory and cognitive decline known to occur in these animals is related to rather subtle changes in the morphological and molecular integrity of neurons subserving identifiable neocortical association circuits that play a critical role in cognition.

Aging↗

PubMed2002

Morphological alterations in neurons forming corticocortical projections in the neocortex of aged Patas monkeys.

Recent studies indicate that the cognitive processes mediated by the prefrontal cortex, such as working memory, are impaired during normal aging. These disturbances in cortical function may be a consequence of abnormalities in neocortical circuits, even though the numbers of cortical neurons are preserved in normal aging. We performed retrograde tract-tracing of cortical projections connecting the temporal cortex to the prefrontal cortex in combination with dye-filling and three-dimensional neuronal reconstructions in aged patas monkeys. Age-related changes affected the apparent complexity of the apical dendrites of projection neurons and caused a significant loss of dendritic spines at all levels of their dendritic trees. These results indicate that normal aging is accompanied by neuronal changes that are quite subtle, and possibly involves discrete cellular components of certain cortical neurons selectively rather than inducing major alterations such as cell death.

Aging↗