Biomedical subjects

J Huguenard

Publications and source records attributed to J Huguenard.

3 recordsLinked to original sources

PubMed1998

Dendritic low-threshold calcium currents in thalamic relay cells.

The low-threshold calcium current (IT) underlies burst generation in thalamocortical (TC) relay cells and plays a central role in the genesis of synchronized oscillations by thalamic circuits. Here we have combined in vitro recordings and computational modeling techniques to investigate the consequences of dendritically located IT in TC cells. Simulations of a reconstructed TC cell were compared with the recordings obtained in the same cell to constrain the values of its passive parameters. T-current densities in soma and proximal dendrites were then estimated by matching the model to voltage-clamp recordings obtained in dissociated TC cells, which lack most of the dendrites. The distal dendritic T-current density was constrained by recordings in intact TC cells, which show 5-14 times larger peak T-current amplitudes compared with dissociated cells. Comparison of the model with the recordings of the same cell constrained further the T-current density in dendrites, which had to be 4.5-7.6 times higher than in the soma to reproduce all experimental results. Similar conclusions were reached using a simplified three-compartment model. Functionally, the model shows that the same amount of T-channels can lead to different bursting behaviors if they are exclusively somatic or distributed throughout the dendrites. In conclusion, this combination of models and experiments shows that dendritic T-currents are necessary to reproduce low-threshold calcium electrogenesis in TC cells. Dendritic T-current may also have significant functional consequences, such as an efficient modulation of thalamic burst discharges by corticothalamic feedback.

Action Potentials↗

PubMed1980

Role of ornithine decarboxylase in cardiac growth and hypertrophy.

Inhibition of cardiac ornithine decarboxylase (ODC) by alpha-difluoromethylornithine (DFMO) did not prevent normal cardiac growth in mature rats but attenuated isoproterenol-induced hypertrophy. Hypertrophy caused by triiodothyronine was not prevented by DFMO. There appear to be both ODC-dependent and ODC-independent processes contributing to the subcellular mechanisms associated with growth, which must be considered in the potential laboratory and clinical use of DFMO.

Animals↗

PubMedDate not supplied

Neurotransmitter control of neocortical neuronal activity and excitability.

The pattern of activity and excitability of cortical neurons and neuronal circuits is dependent upon the interaction between glutamatergic and GABAergic fast-activating transmitter systems as well as the state of the more slowly acting transmitters such as ACh, norepinephrine, 5-HT, and histamine. Through the activation of GABAA receptors, GABAergic neurons regulate the amplitude and duration of EPSPs and, in so doing, control the level of functional activation of NMDA receptors. In contrast, activation of muscarinic, adrenergic, serotoninergic, histaminergic, and glutamate metabotropic receptors controls the excitability and pattern of action potential generation in identified pyramidal cells through increases or decreases in various K+ conductances. Activation of muscarinic, alpha 1-adrenergic, or glutamate metabotropic receptors on layer V burst-generating corticotectal or corticopontine neurons results in depolarization through a reduction in a K+ conductance and a switch in the firing mode from repetitive burst firing to single-spike activity. In contrast, activation of muscarinic, beta-adrenergic, H2-histaminergic, and serotoninergic receptors on regular-spiking layer II/III, V, and/or VI corticogeniculate pyramidal cells results in a decrease in spike frequency adaptation and increased responsiveness to depolarizing inputs through a reduction in a slow Ca(2+)-activated K+ current IAHP, and/or a voltage-dependent K+ current, IM. Through these, and other, mechanisms the spatial and temporal pattern of activity generated in cortical circuits is regulated by both intracortical and extracortical neurotransmitter systems.

Animals↗