Biomedical subjects

K J Gingrich

Publications and source records attributed to K J Gingrich.

4 recordsLinked to original sources

PubMed1991

Modeling the hemodynamic response to dopamine in acute heart failure.

A descriptive incremental nonlinear single-input-multiple-output (SIMO) model of the hemodynamic response [cardiac output (CO) and mean aortic pressure (MAP)] to the inotropic drug dopamine in acute ischemic heart failure was constructed to facilitate the design of closed-loop control systems. The structure of the CO component of the model is a first-order system with a sigmoidal relationship. The MAP component is a first-order system with a threshold. Parameter identification was performed on data collected during positive step (drug on) and negative step (drug off) testing using multiple levels (2-6 mcg/kg/min) of infusion of dopamine in a canine model of acute ischemic heart failure. Parameter estimation utilized a least squares objective function and a linearized form of the step response of the model in the time domain. The model provides good approximations to the mean empirical responses.

Animals↗

PubMed1988

Mathematical model of cellular mechanisms contributing to presynaptic facilitation.

Presynaptic facilitation of transmitter release from sensory neurons is an important mechanism contributing to nonassociative and associative learning in Aplysia. In a previous modeling study (28,29), we concluded that enhancement of the postsynaptic potential (PSP) during presynaptic facilitation is mediated by at least two processes; spike broadening, which has been observed experimentally, and a process that we modeled as mobilization of transmitter. In an effort to gain insight into the relative contribution of these two mechanisms of presynaptic facilitation, we have extended our earlier model to include more detailed descriptions of: a) the kinetics of the Ca2+ channel, b) the diffusion of Ca2+ through the cytoplasm, c) the process of transmitter release, and d) the PSP. The present quantitative model provides an accurate description of the input-output relationship for synapses of sensory neurons, and predicts changes in the shape of postsynaptic potentials as a function of mobilization and spike broadening. The results confirm and extend previous experimental studies (33) and indicated that cellular analogs of sensitization (facilitation of nondecremented responses) is mediated primarily by spike broadening; whereas, analogs of dishabituation (facilitation of depressed responses) require mobilization.

Animals↗

PubMed1987

Single-cell neuronal model for associative learning.

Recently, a novel cellular mechanism, activity-dependent neuromodulation, was identified in sensory neurons mediating the gill and tail withdrawal reflexes in Aplysia. This mechanism may explain associative learning on a behavioral level. The present study was designed to mathematically model subcellular events that may underlie this mechanism and to examine the ability of the model to fit available empirical data. In this associative model, the reinforcing or unconditioned stimulus (US) leads to non-specific enhancement of transmitter release from sensory neurons by activating a cAMP cascade. Spike activity in sensory neurons, the conditioned stimulus (CS), transiently elevates intracellular Ca2+. The CS-triggered increases of intracellular Ca2+ "primes" the cyclase and amplifies the US-mediated cAMP synthesis. As a result of pairing specific amplification of cAMP levels, transmitter release is enhanced beyond that produced by unpaired stimuli or by application of the US alone. The model is capable of fitting empirical data on activity-dependent neuromodulation and predicts a characteristic interstimulus interval (ISI) curve. At the subcellular level, the model's ISI function is related to the time course of the buffering of intracellular Ca2+. The magnitude and duration of the pairing specific enhancement of transmitter release is related to the levels and time course of intracellular cAMP stimulation.

Action Potentials↗

PubMed1985

Simulation of synaptic depression, posttetanic potentiation, and presynaptic facilitation of synaptic potentials from sensory neurons mediating gill-withdrawal reflex in Aplysia.

The defensive gill-withdrawal reflex in Aplysia has proven to be an attractive system for analyzing the neural mechanisms underlying simple forms of learning such as habituation, sensitization, and classic conditioning. Previous studies have shown that habituation is associated with synaptic depression and sensitization with presynaptic facilitation of transmitter release from sensory neurons mediating the reflex. The synaptic depression, in turn, is associated with a decrease in Ca2+ currents in the sensory neurons, whereas presynaptic facilitation with increased Ca2+ currents produced indirectly by a decrease in a novel serotonergic sensitive K+ current. The present work represents an initial quantitative examination of the extent to which these mechanisms account for each of these types of synaptic plasticity. To address these issues a lumped parameter mathematical model of the sensory neuron release process was constructed. Major components of this model include Ca2+-channel inactivation, Ca2+-mediated neurotransmitter release and mobilization, and readily releasable and upstream feeding pools of neurotransmitter. In the model, release of neurotransmitter has a linear function of Ca2+ concentration and is not affected directly by residual Ca2+. The model not only simulates the data of synaptic depression and recovery from depression, but also qualitatively predicts other features of neurotransmitter release that it was not designed to fit. These include features of synaptic depression with high and low levels of transmitter release, posttetanic potentiation, a steep relationship between action potential duration and transmitter release, enhanced release produced by broadening the sensory neuron action potential (presynaptic facilitation), and dramatic synaptic depression with two closely spaced tetraethylammonium (TEA) spikes. The model cannot account fully for synaptic depression with empirically observed somatic Ca2+-current kinetics. Rather a large component of synaptic depression is due to reduction to the pools of releasable neurotransmitter (depletion). In the model when spike durations are greater than 15-20 ms, spike broadening produces little facilitation. However, when spike durations are more physiological, spike broadening leads to enhanced transmitter release.

Animals↗