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K Harsanyi

Publications and source records attributed to K Harsanyi.

8 recordsLinked to original sources
PubMed1997

Transient synaptic potentiation in the visual cortex. I. Cellular mechanisms.

The cellular mechanisms that underlie transient synaptic potentiation were studied in visual cortical slices of adult guinea pigs (> or = age 5 wk postnatal). Postsynaptic potentials (PSPs) elicited by stimulation of the white matter/layer VI border were recorded with conventional intracellular techniques from layer II/III neurons. Transient potentiation (average duration 23 +/- 3 min, mean +/- SE) was evoked by 60 low-frequency (0.1 Hz) pairings of weak afferent stimulation with coincident intracellular depolarizing pulses (80 ms) of the postsynaptic cell. Fifty-one percent (47 of 92) of the pairing protocols led to significant enhancement (+26 +/- 3%) of the PSP peak amplitude. Blockade of action potential output from the recorded neuron during pairing with Lidocaine, N-ethyl bromide quaternary salt in the recording micropipette did not reduce the likelihood of potentiation (7 of 14 protocols = 50%). Thus transient synaptic potentiation does not require action potential output from the paired cell or recurrent synaptic activation in the local cortical circuit. Rather, the modification occurs at synaptic sites that directly impinge onto the activated neuron. Intracellular postsynaptic blockade of inhibitory PSPs only onto the paired cell with the chloride channel blocker 4,4'-dinitro-stilbene-2,2'-disulfonic acid and the potassium channel blocker cesium in he micropipette also did not reduce the likelihood of induction of potentiation (6 of 9 protocols = 67%). These results suggest that the potentiation is due to a true upregulation of excitatory synaptic transmission and that it does not require a reduction of inhibitory components of the compound PSP for induction. Chelation of postsynaptic intracellular calcium with 1,2-bis-2-aminophenoxy ethane-N,N,N',N'-tetraacetic acid (BAPTA) in all cases effectively blocked the induction of potentiation (no change in the PSP, 9 of 13 protocols; induction of synaptic depression, 4 of 13 protocols), suggesting that a rise in the intracellular postsynaptic calcium level is critical for the pairing-induced synaptic potentiation to occur. Bath application of the N-methyl-D-aspartate (NMDA) receptor antagonist 2-amino-5-phosphonovaleric acid (APV) reversibly blocked potentiation of the PSP peak amplitude in most cells (14 of 16) that were capable of significant potentiation of control solution. Blockade of nitric oxide production with bath application of the competitive inhibitor of nitric oxide synthase, L-nitro-arginine (LNA), did not significantly affect the likelihood of synaptic potentiation (11 of 20 cells). It did, however, block subsequent enhancement for several cells (2 of 4) that had previously had their inputs potentiated. Moreover, LNA increased the overall average magnitude of synaptic potentiation (with an additional +28%) when induction was successful. These results suggest that endogenous cortical nitric oxide production can both positively and negatively modulate this NMDA receptor-mediated type of synaptic plasticity.

Animals↗
PubMed1997

Transient synaptic potentiation in the visual cortex. II. Developmental regulation.

In our previous study, pairing-induced transient synaptic potentiation in supragranular layers of the visual cortex was described in mature guinea pigs. In the present study, the development of this type of synaptic plasticity and the underlying cellular mechanisms that mediate it were evaluated in animals from postnatal day (PND) 5 to 180. Potentiation is more reliably evoked in younger animals (likelihood: 75%, PND 5-30; 51%, PND > or = 34), and the magnitude of the effect is greater (+40 +/- 3%, mean +/- SE, PND 5-30; +26 +/- 3%, PND > or = 34). Similar to data obtained from the mature animals, visual cortical transient synaptic potentiation in the immature cortex occurs at excitatory synaptic sites directly activated by the stimulation, and activation by local recurrent cortical circuits is not necessary for the induction of this potentiation. This is demonstrated by 1) experiments in which action potential output from the paired neuron was blocked by Lidocaine, N-ethyl bromide quaternary salt applied into the neuron (5 of 5), and 2) experiments in which the contribution to the compound postsynaptic potential by inhibitory synapses was eliminated by selective, intracellular blockade by gamma-aminobutyric acid-mediated inhibitory postsynaptic potentials only onto the recorded neuron (7 of 11). Thus these perturbations do not reduce the likelihood or magnitude of this synaptic potentiation. In contrast to the N-methyl-D-aspartate (NMDA) receptor dependence for induction of this synaptic potentiation in the cortex of mature animals, in the young animals' cortices (PND 11-27) potentiation is readily induced during blockade of NMDA receptors (72%, 13 of 18, did not different from control: 75%, 40 of 53). Thus the NMDA receptor becomes functionally linked to a synaptic potentiation cascade during development, replacing another 2-amino-5-phosphonovaleric acid (APV)-insensitive potentiation process in the neonatal cortex. Postsynaptic intracellular calcium has a critical role in the induction of this form of synaptic potentiation in all ages studied. Synaptic potentiation was prevented (8 of 11 cases) or was replaced by synaptic depression (3 of 11 cells) in experiments in which postsynaptic calcium levels were reduced by intracellular application of 1,2-bis-2-aminophenoxy ethane-N,N,N',N'-tetraacetic acid (BAPTA) in the cortex of young (PND 7-14) animals, or in which the extracellular calcium concentrations was lowered. Inhibition of postsynaptic calcium-induced calcium release blocked synaptic potentiation (4 of 4 cells). Prolonged superfusion (3 h) of the nitric oxide synthase inhibitor L-nitro-arginine (LNA) did not significantly affect the likelihood (in LNA, 81%; 13 of 16 cells), or the magnitude (+38 +/- 7% increase in LNA vs. +40 +/- 3% in control cases) of potentiation, in contrast to its effects in the mature cortex.

Aging↗
PubMed1997

Endogenous activation of dopamine D2 receptors regulates dopamine release in the fish retina.

In the fish retina, horizontal cell electrical coupling and light responsiveness is regulated by activation of dopamine D1 receptors that are located on the horizontal cells themselves. The effects of dopamine and dopamine D2 receptor agonists and antagonists on cone horizontal cell light responses were studied in in vitro superfused goldfish retinas. Horizontal cell light responses and electrical coupling were assessed by monitoring responses to full-field stimuli and to small, centered (0.4 mm diam) spots of light, respectively. Dopamine (0.2-10 microM) application uncoupled horizontal cells and decreased their responses to full-field stimuli. Application of the D2 antagonist eticlopride (10-50 microM) produced similar effects, whereas quinpirole (0.1-10 microM), a D2 agonist, had the opposite effects. The uncoupling effect of eticlopride was blocked by prior application of SCH23390 (10 microM), a D1 receptor antagonist, and was eliminated after destruction of dopaminergic neurons by prior treatment of the retinas with 6-hydroxydopamine. The effects of these D2 drugs were observed following flickering light stimulation, but were not observed following sustained light stimulation. Application of the D2 antagonists sulpiride (0.5-20 microM) and spiperone (0.25-10 microM) uncoupled horizontal cells when the total concentration of divalent cations (Mg2+ and Ca2+) in the Ringer solution was 1.1 mM. However, when the concentration of divalent cations was 0.2 mM, spiperone had no effect on the horizontal cells and sulpiride increased coupling. In contrast, eticlopride uncoupled the cells and decreased their light responsiveness irrespective of the concentration of divalent cations. The effects of quinpirole also depended on the concentration of divalent cations; its coupling effect was reduced when the divalent cation concentration was increased from 0.2 to 1.0 mM. The results suggest that activation of D2 receptors in the fish retina by endogenous dopamine decreases dopamine release and is greater after flickering compared with sustained light stimulation. These D2 receptors thus function as presynaptic autoreceptors that inhibit dopamine release from dopaminergic cells. In addition, the results also indicate that the effectiveness of some D2 drugs at these receptors is dependent on the concentration of divalent cations.

Animals↗
PubMed1996

Mechanisms for regulating synaptic efficiency in the visual cortex.

Brief epochs of pairing of low frequency synaptic activation and postsynaptic depolarization, in vitro, in supragranular neurons of nature guinea-pig visual cortex lead to a transient (20-60 min) synaptic potentiation. The process is due to a true up-regulation of excitatory synapse efficiency onto the activated neuron. The potentiation requires NMDA receptor activation and a postsynaptic calcium signal for induction and it is modifiable by endogenous nitric oxide (NO) production in the mature cortex. In the cortex of young animals (< PND 21), the pairing-induced potentiation is robust and depends on a postsynaptic calcium signal but it is independent of NMDA receptor activation and NO production. The ability of cortical synaptosomes to release endogenous glutamate is enhanced by NMDA receptor activation and this enhancement is NO-dependent. The NO signal, however, does not amplify the glutamate release of all synapses but only those that have activated voltage-gated calcium channels and were presumably more active at the time of the NO signal. Electrophysiological recordings from visual cortical neurons in anesthetized cats with local iontophoresis of compounds that inhibit or facilitate endogenous cortical NO production reveal the capacity for NO to modulate visual responses in vivo. NO appears to act in the intact cortex by amplifying signals of visual inputs that were co-active at the time of the NO production. The adult visual cortex is capable of dramatic alterations in synaptic efficiency over brief periods suggesting a dynamic cortical network. NMDA receptors and nitric oxide contribute to these processes.

Algorithms↗
PubMed1996

Activation of NMDA receptors produces dopamine-mediated changes in fish retinal horizontal cell light responses.

1. The action of N-methyl-D-aspartate (NMDA) on cone horizontal cells was studied in in vitro goldfish retinas superfused with a bicarbonate-based Ringer solution that contained D-serine (0.5 microM), a glycine analogue, but no added Mg2+. Horizontal cell light responses and electrical coupling were assessed by monitoring responses to full-field stimuli and to small, centered (0.4 mm diam) spots of light, respectively. 2. NMDA uncoupled horizontal cells, reduced their light responsiveness, and acted in a dose-dependent manner, with threshold at 10 microM and maximum effect at 100 microM. 3. Application of the NMDA antagonists DL-2-amino-7-phosphonoheptanoic acid-AP-5) or D-2-amino-5-phosphonopentanoic acid-AP-5) (50 microM) blocked the uncoupling action of NMDA (100 microM), as did prior application of SCH23390, a dopamine D1 antagonist, or prior treatment of the retinas with 6-hydroxydopamine, a procedure that destroys dopaminergic neurons. 4. Addition of Mg2+ (1 mM) partially blocked the effects of NMDA at 100 microM and completely blocked the effects of 50 microM NMDA. The effects of NMDA (50 or 100 microM) were also reduced if it was applied without D-serine. 5. Both flickering (5 Hz) and sustained light stimulation uncoupled horizontal cells and reduced their light responsiveness. Application of AP-7 blocked the effects of flickering light stimulation, but did not block the effects of sustained light. 6. These results suggest that activation of NMDA receptors in the fish retina uncouples cone horizontal cells and decreases their light responsiveness by increasing dopamine release. The results further suggest that flickering light, but not sustained light, increases the release of dopamine through activation of NMDA receptors.

Animals↗
PubMed1992

Activation of a D2 receptor increases electrical coupling between retinal horizontal cells by inhibiting dopamine release.

In the fish retina, interplexiform cells release dopamine onto cone-driven horizontal cells. Dopamine decreases the electrical coupling between horizontal cells by activating adenylate cyclase through dopamine D1 receptors. Using intracellular recording, we have studied the effect of dopamine D2 receptor activation on horizontal cell electrical coupling in the intact goldfish retina. Superfusion of the D2 agonist LY171555 (quinpirole; 0.2-10 microM) increased horizontal cell coupling, as indicated by a decrease in responses to centered spots or slits of light. The length constant of the horizontal cell network increased an average of 31%. Although dopamine (0.5-20 microM) uncoupled horizontal cells, lower concentrations (e.g., 0.2 microM) initially uncoupled and then subsequently increased coupling beyond initial control levels. The coupling effect of LY171555 (10 microM) was blocked completely by prior application of the D1 agonist SKF 38393 at saturating (20 microM) or nonsaturating (2.5-5.0 microM) doses. Prior treatment of the retinas with 6-hydroxydopamine, which destroyed dopaminergic neurons, eliminated the coupling effect of LY171555 but not the uncoupling effect of SKF 38393. These results suggest that goldfish horizontal cells contain D1, but not D2, receptors and that dopamine activation of D2 autoreceptors on interplexiform cells inhibits dopamine release onto horizontal cells so that the electrical coupling between horizontal cells increases.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMedDate not supplied

Modulation of cone to horizontal cell transmission by calcium and pH in the fish retina.

The effects of small changes in the calcium and sodium concentrations and in the pH of superfusion medium on the membrane potential and light-evoked responses of cone horizontal cells in the goldfish retina were examined. Conventional intracellular recording, a bicarbonate-based superfusion medium, and a specially designed superfusion apparatus that reduced pressure wave disturbances were used. An increase in the extracellular calcium concentration, [Ca2+]o, from control levels (0.1 mM) to 1.0 mM hyperpolarized cone horizontal cells and reduced the magnitude of their light responses at all stimulus intensities. Addition of 20 mM NaCl to the 1.0 mM Ca2+ Ringer's solution reversed the hyperpolarizing effect of the 1.0 mM Ca2+ but addition of 20 mM choline, a monovalent cation that does not pass through cyclic GMP-activated channels, did not. Reduction of the superfusate pH from 7.6 to 7.2 by switching from a Ringer's solution gassed with 3% CO2 to one gassed with 10% CO2 hyperpolarized horizontal cells and reduced the magnitude of their light responses at all stimulus intensities for both 0.1 and 1.0 mM Ca2+ Ringer's solutions. An increase in pH to 8.2 by gassing the superfusate with 1% CO2 slightly depolarized the cells in 0.1 mM Ca2+ Ringer's solution but slightly hyperpolarized the cells in the 1.0 mM Ca2+ Ringer's solution. Following pharmacological isolation of the horizontal cells from synaptic input with high doses of glutamate (4-5 mM) and/or Co2+ (4 mM) treatment, no effect on horizontal cell membrane potential due to changes in pHo or [Ca2+]o was observed. These findings are discussed with respect to the cellular mechanisms and sites of action in the outer retina that are affected by changes in pHo and [Ca2+]o.

Animals↗