Ronald Millecchia

Using the Gompertz-Strehler model of aging and mortality to explain mortality trends in industrialized countries.

Mortality trends in industrialized countries are characterized by declines in vascular disease (ischemic heart disease and stroke) and rises in cancers and degenerative diseases. These trends are typically analyzed by examining each disorder in isolation using the perspective of genetic and environmental influences. However, longitudinal Gompertzian analysis and the Gompertz-Strehler model of aging and mortality as modified by Lestienne suggest that age-specific mortality rates, for both general and disease-specific mortality, are an interrelated deterministic function of aggregate genetic, environmental and competitive influences. Consequently, evolving mortality trends and patterns appear to be influenced by three factors (with deterministic competition being the third factor), rather than just two factors (genetic and environmental) as commonly depicted.

Automatic nerve impulse identification and separation.

Abstract A heuristic method was developed to identify and to separate automatically unit nerve impulses from a multiunit recording. Up to 20 distinct units can be identified. The method can sequentially decompose superimposed nerve impulses if the rapidly changing region of at least one of them is relatively undistorted. The identification and separation procedure has been successfully applied to the extracellularly recorded neural activity associated with the shadow reflex pathway of the barnacle. The limitations of the procedure are discussed and additional applications of the technique are presented.

Spatial convergence and divergence between cutaneous afferent axons and dorsal horn cells are not constant.

We have proposed a quantitative model of the development of dorsal horn cell receptive fields (RFs) and somatotopic organization (Brown et al. [1997] Somatosens. Motor Res. 14:93–106). One component of that model is a hypothesis that convergence and divergence of connections between low‐threshold primary afferent mechanoreceptive axons and dorsal horn cells are invariant over skin location and dorsal horn location. The more limited, and more easily tested, hypothesis that spatial convergence and divergence between cutaneous mechanoreceptors and dorsal horn cell are constant was examined. Spatial divergence is the number of dorsal horn cells whose RFs overlap the RF center of a primary afferent, and spatial convergence is the number of afferent RF centers that lie within the RF of a dorsal horn cell. Innervation density was determined as a function of location on the hindlimb by using peripheral nerve recording and axon counting. A descriptive model of dorsal horn cell receptive fields (Brown et al. [1998] J. Neurophysiol. 31:833–848) was used to simulate RFs of the entire dorsal horn cell population in order to estimate RF area and map scale as a function of location on the hindlimb. Previously reported correlations among innervation density, map scale, and RF size were confirmed. However, these correlations were not linear. The hypothesis that spatial convergence and divergence are constant was rejected. The previously proposed model of development of dorsal horn cell somatotopy and RF geometries must be revised to take variable spatial convergence and divergence into account. J. Comp. Neurol. 420:277–290, 2000.

From innervation density to tactile acuity 2:: Embryonic and adult pre- and postsynaptic somatotopy in the dorsal horn

We tested the hypothesis that dorsal horn laminae III-IV cell receptive fields (RFs) are initially established in three steps: cutaneous axons penetrate the dorsal horn near their rostrocaudal (RC) levels of entry into the spinal cord. Their terminal branches distribute mediolaterally (ML) according to their relative distoproximal RF locations on the leg, and form nonselective synapses with nearby dorsal horn cell dendrites, establishing the initial dorsal horn cell RFs. Rootlet axon RFs in adult cats were used to approximate the RC entry levels of hindlimb skin input. Cord dorsum recordings of monosynaptic field potentials evoked by electrical skin stimulation provided the RC distributions of synaptic input. These were in close agreement. Simulated projections of all 22,000 hindlimb axons were similar to projections predicted from EPSP distributions, and with the observed projections of dorsal roots, cutaneous nerves, and individual axons. The simulated terminals were connected nonselectively to nearby dendrites of 135,000 simulated lamina III-IV cells whose dendritic surface area distributions were based on intracellularly stained cells. There was an overall similarity among pre- and postsynaptic embryonic and adult somatotopies, with a progressive transformation of RF angular location as a function of RC, ML dorsal horn location from an initial embryonic presynaptic concentric pattern to an adult postsynaptic radial one. The initial embryonic dorsal horn cell RF assembly hypothesis was supported by the simulations, as was the additional hypothesis that further refinement of connections would be necessary to establish sufficient selectivity to account for observed adult RFs and somatotopy.

Variation of dorsal horn cell dendritic spread with map scale.

Cells in laminae III, IV, and V of cat dorsal horn were injected with horseradish peroxidase or neurobiotin. Dorsal views of the dendritic domains were constructed in order to measure their lengths, widths, areas, and length/width ratios in the horizontal plane (the plane of the somatotopic map). Dendritic domain width and area in the horizontal plane were negatively correlated with fractional distance between the medial and lateral edges of the dorsal horn. These results are consistent with the hypothesis that dendritic domain width varies with map scale, which is maximal in the medial dorsal horn. This is similar to the variation in widths of primary afferent bouton distributions.