Dopaminergic Regulation of Neuronal Excitability through Modulation ofI_hin Layer V Entorhinal Cortex

Abstract

The entorhinal cortex (EC) is a significant component of the systems that underlie certain forms of memory formation and recall. Evidence has been emerging that the dopaminergic system in the EC facilitates these and other functions of the EC. The effects of dopamine (DA) on membrane properties and excitability of EC neurons, however, are not known. We used in vitro whole-cell patchclamp recordings from layer V pyramidal neuronal somata and dendrites of the adult rat lateral EC to investigate the effects of DA on the excitability of these neurons. We found that brief application of DA caused a reduction in the excitability of layer V EC pyramidal neurons. This effect was attributable to voltage-dependent modification of membrane properties that can best be explained by an increase in a hyperpolarization-activated conductance. Furthermore, the effects of DA were blocked by pharmacological blockade of h-channels, but not by any of a number of other ion channels. These actions were produced by a D 1 receptor-mediated increase of cAMP but were independent of protein kinase A. A portion of the actions of DA can be attributed to effects in the apical dendrites. The data suggest that DA can directly influence the membrane properties of layer V EC pyramidal neurons by modulation of h-channels. These actions may underlie some of the effects of DA on memory formation.

D1-Receptor Impact on Neuroplasticity in Humans

“…The inhibitory effect of D 1 -receptor activity on acute motor cortex excitability is compatible with former animal experiments (Gorelova et al, 2002;Rosenkranz and Johnston, 2006;Kröner et al, 2007).…”

Dendritic HCN2 Channels Constrain Glutamate-Driven Excitability in Reticular Thalamic Neurons

“…This suggests that I h may serve distinct functions in RTN and VB neurons. I h has been shown to regulate tonic action potential firing in entorhinal cortex pyramidal cells (Rosenkranz and Johnston, 2006) and striatal cholinergic interneurons (Deng et al, 2007). Here, ZD7288 effects on tonic single spike firing were observed at relatively depolarized membrane potentials (approximately Ϫ50 mV) (Fig.…”

Dynamics of Intracellular Oxygen in PC12 Cells upon Stimulation of Neurotransmission

“…Spontaneous NT release, which occurs randomly in the cell population, activates individual cells, making them resistant to sustained population-wide stimulation with high e K ϩ . In contrast, TeNT (ϩ) cells, which are exposed to lower levels of dopamine, become more excitable than intact cells (50,51). This effect is rather nonspecific because TeNT (ϩ) cells respond more actively to FCCP and ionomycin.…”

“…We think that reduced exposure of TeNT (ϩ) cells to NT can up-regulate their excitability, because dopamine was shown to suppress the responses of entorhinal cortex and striatal neurons to excitation (50,51). Taken together, these results indicate that high e K ϩ activates respiration regardless of the efficiency of NT exocytosis in PC12 cells.…”