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Andrey V Dmitriev

Publications and source records attributed to Andrey V Dmitriev.

5 recordsLinked to original sources
PubMed2006

Dendritic compartmentalization of chloride cotransporters underlies directional responses of starburst amacrine cells in retina.

The mechanisms in the retina that generate light responses selective for the direction of image motion remain unresolved. Recent evidence indicates that directionally selective light responses occur first in the retina in the dendrites of an interneuron, i.e., the starburst amacrine cell, and that these responses are highly sensitive to the activity of Na-K-2Cl (NKCC) and K-Cl (KCC), two types of chloride cotransporter that determine whether the neurotransmitter GABA depolarizes or hyperpolarizes neurons, respectively. We show here that selective blockade of the NKCC2 and KCC2 cotransporters located on starburst dendrites consistently hyperpolarized and depolarized the starburst cells, respectively, and greatly reduced or eliminated their directionally selective light responses. By mapping NKCC2 and KCC2 antibody staining on these dendrites, we further show that NKCC2 and KCC2 are preferentially located in the proximal and distal dendritic compartments, respectively. Finally, measurements of the GABA reversal potential in different starburst dendritic compartments indicate that the GABA reversal potential at the distal dendrite is more hyperpolarized than at the proximal dendrite due to KCC2 activity. These results thus demonstrate that the differential distribution of NKCC2 on the proximal dendrites and KCC2 on the distal dendrites of starburst cells results in a GABA-evoked depolarization and hyperpolarization at the NKCC2 and KCC2 compartments, respectively, and underlies the directionally selective light responses of the dendrites. The functional compartmentalization of interneuron dendrites may be an important means by which the nervous system encodes complex information at the subcellular level.

Amacrine Cells↗
PubMed2005

Electrical feedback in the cone pedicle: a computational analysis.

One of the fundamental principles of neuroscience is that direct electrical interactions between neurons are not possible without specialized electrical contacts, gap junctions, because the transmembrane resistance of neurons is typically much higher than the resistance of the adjacent extracellular space. However it has been proposed that in the retina direct electrical interactions between cones and second-order neurons occur due to the specific morphology of the cone synaptic terminal. This electrical mechanism could potentially explain the phenomenon of "negative feedback" from horizontal cells to cones and the recent finding that the tips of horizontal cell dendrites contain hemichannels has rekindled interest in the idea. We quantitatively evaluated the possibility that hemichannels and/or glutamate channels mediate electrical feedback from horizontal cells to cones. The calculations show that it is unlikely that an electrical mechanism plays a significant functional role because 1) the necessity of preserving adequate cone-to-horizontal-cell synaptic transmission limits the extracellular space resistance and the horizontal-cell dendritic transmembrane resistances to values at which the effectiveness of electrical feedback is very low and its electrical effect on the cone presynaptic membrane is negligible, 2) electrical feedback is most effective in the dark and weaker during light adaptation, which contradicts the experimental data, and 3) electrical negative feedback is associated with much stronger electrical positive feedback from horizontal cells to cones, a phenomenon that has never been reported. Therefore it is likely that negative feedback from horizontal cells to cones is chemical in nature.

Animals↗
PubMed2004

Retinal pH reflects retinal energy metabolism in the day and night.

The extracellular pH of living tissue in the retina and elsewhere in the brain is lower than the pH of the surrounding milieu. We have shown that the pH gradient between the in vitro retina and the superfusion solution is regulated by a circadian (24-h) clock so that it is smaller in the subjective day than in the subjective night. We show here that the circadian changes in retinal pH result from a clock-mediated change in the generation of H+ that accompanies energy production. To demonstrate this, we suppressed energy metabolism and recorded the resultant reduction in the pH difference between the retina and superfusate. The magnitude of the reduction in the pH gradient correlated with the extent of energy metabolism suppression. We also examined whether the circadian-induced increase in acid production during the subjective night results from an increase in energy metabolism or from the selective activation of glycolysis compared with oxidative phosphorylation. We found that the selective suppression of either oxidative phosphorylation or glycolysis had almost identical effects on the dynamics and extent of H+ production during the subjective day and night. Thus the proportion of glycolysis and oxidative phosphorylation is maintained the same regardless of circadian time, and the pH difference between the tissue and superfusion solution can therefore be used to evaluate total energy production. We conclude that circadian clock regulation of retinal pH reflects circadian regulation of retinal energy metabolism.

Animals↗
PubMed2003

Cation--chloride cotransporters mediate neural computation in the retina.

The ability of directionally selective (DS) retinal ganglion cells to respond selectively to stimulus motion in one direction is a classic unresolved example of computation in a local neural circuit. Recent evidence indicates that DS responses occur first in the retina in the dendrites of starburst amacrine cells (interneurons presynaptic to the ganglion cells). We report that the directional responses of starburst-cell dendrites and DS ganglion cells are highly sensitive to the polarity of the transmembrane chloride gradient. Reducing the transmembrane chloride gradient by ion substitution or by blocking the K-Cl cotransporter resulted in the starburst cells responding equally to light moving in opposite directions. Conversely, increasing the chloride gradient by blocking the Na-K-Cl cotransporter eliminated responses to light moving in either direction. Moreover, in each case, blocking the chloride cotransporters or reducing the transmembrane chloride gradient eliminated the directional responses of DS ganglion cells in a manner opposite that of the starburst cells. These results indicate that chloride cotransporters play a key role in the generation of direction selectivity and that the directional responses of starburst cells and DS ganglion cells are exquisitely sensitive to the chloride equilibrium potential. The findings further suggest that the directional responses of DS ganglion cells are mediated in part by the directional release of gamma-aminobutyric acid from starburst dendrites and that the asymmetric distribution of the two cotransporters along starburst-cell dendrites mediates direction selectivity. A model of direction selectivity in the retina that incorporates these and other findings is discussed.

Animals↗