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Dopaminergic suppression of synaptic transmission in the lateral entorhinal cortex.

Caruana DA, Chapman CA - Neural Plast. (2008)

Bottom Line: We have found that low concentrations of dopamine facilitate field EPSPs in the entorhinal cortex, and that higher concentrations of dopamine suppress synaptic responses.Dopamine also lowered input resistance, and reduced the number of action potentials evoked by depolarizing current steps.The drop in input resistance was mediated by activation of D(1)-like receptors, and was prevented by blocking K(+) channels with TEA.

View Article: PubMed Central - PubMed

Affiliation: Department of Psychology, Center for Studies in Behavioral Neurobiology, Concordia University, Montréal, Québec, Canada.

ABSTRACT
Dopaminergic projections to the superficial layers of the lateral entorhinal cortex can modulate the strength of olfactory inputs to the region. We have found that low concentrations of dopamine facilitate field EPSPs in the entorhinal cortex, and that higher concentrations of dopamine suppress synaptic responses. Here, we have used whole-cell current clamp recordings from layer II neurons to determine the mechanisms of the suppression. Dopamine (10 to 50 microM) hyperpolarized membrane potential and reversibly suppressed the amplitude of EPSPs evoked by layer I stimulation. Both AMPA- and NMDA-mediated components were suppressed, and paired-pulse facilitation was also enhanced indicating that the suppression is mediated largely by reduced glutamate release. Blockade of D(2)-like receptors greatly reduced the suppression of EPSPs. Dopamine also lowered input resistance, and reduced the number of action potentials evoked by depolarizing current steps. The drop in input resistance was mediated by activation of D(1)-like receptors, and was prevented by blocking K(+) channels with TEA. The dopaminergic suppression of synaptic transmission is therefore mediated by a D(2) receptor-dependent reduction in transmitter release, and a D(1) receptor-dependent increase in a K(+) conductance. This suppression of EPSPs may dampen the strength of sensory inputs during periods of elevated mesocortical dopamine activity.

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High concentrations of dopamine increasepaired-pulse facilitation. (a) Pairs of stimulation pulses with a 30 millisecond interpulse intervalwere delivered before and after 5-minute bath application of 50 μMdopamine. Averaged traces at left showresponses recorded before (ACSF) and after (DA) dopamine from a representativecell. Note the suppression of theresponse to the first pulse and the large facilitation of the second responsefollowing dopamine (dotted line). Tracesat right have been scaled to the amplitude of the first response in normal ACSFto aid comparison. Group data are shownon the right. (b) Paired-pulsefacilitation was also enhanced by 10 μM dopamine. (c) In contrast, the low concentration of 1 μMdopamine does not affect paired-pulse ratio.
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fig2: High concentrations of dopamine increasepaired-pulse facilitation. (a) Pairs of stimulation pulses with a 30 millisecond interpulse intervalwere delivered before and after 5-minute bath application of 50 μMdopamine. Averaged traces at left showresponses recorded before (ACSF) and after (DA) dopamine from a representativecell. Note the suppression of theresponse to the first pulse and the large facilitation of the second responsefollowing dopamine (dotted line). Tracesat right have been scaled to the amplitude of the first response in normal ACSFto aid comparison. Group data are shownon the right. (b) Paired-pulsefacilitation was also enhanced by 10 μM dopamine. (c) In contrast, the low concentration of 1 μMdopamine does not affect paired-pulse ratio.

Mentions: Paired-pulse tests were used todetermine if synaptic suppression and facilitation effects were likelyexpressed pre- or postsynaptically. Pairs of pulses were delivered before and after 5-minute dopamineapplication, and a 30-millisecond interpulse interval was used that results inoptimal paired-pulse facilitation [13, 44–46]. If EPSPs are reduced through a reduction intransmitter release, then a greater amount of transmitter should be availablefor release in response to the second stimulation pulse and paired-pulsefacilitation should be enhanced [47–49]. Changes in EPSPs mediated by alterations inpostsynaptic receptors, however, should not be associated with changes inpaired-pulse ratio. High concentrationsof dopamine that reduced EPSP amplitude were also found to enhance paired-pulsefacilitation (see Figures 2(a), 2(b); t13 = 2.78, P < .05 for 10 μM; t8 = 2.97, P < .05 for 50 μM), suggesting that dopamine reduced EPSPs bysuppressing glutamate release. Incontrast, the low concentration of 1 μM dopamine that facilitated EPSPs had nosignificant effect on paired pulse facilitation (see Figure 2(c)), suggestingthat the facilitation of EPSPs was mediated primarily by an increasedpostsynaptic response to glutamate. Thedopaminergic facilitation of the conditioning response was smaller duringpaired-pulse tests in which stimulus intensity was reduced to avoid spiking (seeFigures 1(c) versus 2(c)) but a similar dopaminergic facilitation of fEPSPs withno effect on paired-pulse ratio has been observed in the entorhinal cortex in vivo [29].


Dopaminergic suppression of synaptic transmission in the lateral entorhinal cortex.

Caruana DA, Chapman CA - Neural Plast. (2008)

High concentrations of dopamine increasepaired-pulse facilitation. (a) Pairs of stimulation pulses with a 30 millisecond interpulse intervalwere delivered before and after 5-minute bath application of 50 μMdopamine. Averaged traces at left showresponses recorded before (ACSF) and after (DA) dopamine from a representativecell. Note the suppression of theresponse to the first pulse and the large facilitation of the second responsefollowing dopamine (dotted line). Tracesat right have been scaled to the amplitude of the first response in normal ACSFto aid comparison. Group data are shownon the right. (b) Paired-pulsefacilitation was also enhanced by 10 μM dopamine. (c) In contrast, the low concentration of 1 μMdopamine does not affect paired-pulse ratio.
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2519792&req=5

fig2: High concentrations of dopamine increasepaired-pulse facilitation. (a) Pairs of stimulation pulses with a 30 millisecond interpulse intervalwere delivered before and after 5-minute bath application of 50 μMdopamine. Averaged traces at left showresponses recorded before (ACSF) and after (DA) dopamine from a representativecell. Note the suppression of theresponse to the first pulse and the large facilitation of the second responsefollowing dopamine (dotted line). Tracesat right have been scaled to the amplitude of the first response in normal ACSFto aid comparison. Group data are shownon the right. (b) Paired-pulsefacilitation was also enhanced by 10 μM dopamine. (c) In contrast, the low concentration of 1 μMdopamine does not affect paired-pulse ratio.
Mentions: Paired-pulse tests were used todetermine if synaptic suppression and facilitation effects were likelyexpressed pre- or postsynaptically. Pairs of pulses were delivered before and after 5-minute dopamineapplication, and a 30-millisecond interpulse interval was used that results inoptimal paired-pulse facilitation [13, 44–46]. If EPSPs are reduced through a reduction intransmitter release, then a greater amount of transmitter should be availablefor release in response to the second stimulation pulse and paired-pulsefacilitation should be enhanced [47–49]. Changes in EPSPs mediated by alterations inpostsynaptic receptors, however, should not be associated with changes inpaired-pulse ratio. High concentrationsof dopamine that reduced EPSP amplitude were also found to enhance paired-pulsefacilitation (see Figures 2(a), 2(b); t13 = 2.78, P < .05 for 10 μM; t8 = 2.97, P < .05 for 50 μM), suggesting that dopamine reduced EPSPs bysuppressing glutamate release. Incontrast, the low concentration of 1 μM dopamine that facilitated EPSPs had nosignificant effect on paired pulse facilitation (see Figure 2(c)), suggestingthat the facilitation of EPSPs was mediated primarily by an increasedpostsynaptic response to glutamate. Thedopaminergic facilitation of the conditioning response was smaller duringpaired-pulse tests in which stimulus intensity was reduced to avoid spiking (seeFigures 1(c) versus 2(c)) but a similar dopaminergic facilitation of fEPSPs withno effect on paired-pulse ratio has been observed in the entorhinal cortex in vivo [29].

Bottom Line: We have found that low concentrations of dopamine facilitate field EPSPs in the entorhinal cortex, and that higher concentrations of dopamine suppress synaptic responses.Dopamine also lowered input resistance, and reduced the number of action potentials evoked by depolarizing current steps.The drop in input resistance was mediated by activation of D(1)-like receptors, and was prevented by blocking K(+) channels with TEA.

View Article: PubMed Central - PubMed

Affiliation: Department of Psychology, Center for Studies in Behavioral Neurobiology, Concordia University, Montréal, Québec, Canada.

ABSTRACT
Dopaminergic projections to the superficial layers of the lateral entorhinal cortex can modulate the strength of olfactory inputs to the region. We have found that low concentrations of dopamine facilitate field EPSPs in the entorhinal cortex, and that higher concentrations of dopamine suppress synaptic responses. Here, we have used whole-cell current clamp recordings from layer II neurons to determine the mechanisms of the suppression. Dopamine (10 to 50 microM) hyperpolarized membrane potential and reversibly suppressed the amplitude of EPSPs evoked by layer I stimulation. Both AMPA- and NMDA-mediated components were suppressed, and paired-pulse facilitation was also enhanced indicating that the suppression is mediated largely by reduced glutamate release. Blockade of D(2)-like receptors greatly reduced the suppression of EPSPs. Dopamine also lowered input resistance, and reduced the number of action potentials evoked by depolarizing current steps. The drop in input resistance was mediated by activation of D(1)-like receptors, and was prevented by blocking K(+) channels with TEA. The dopaminergic suppression of synaptic transmission is therefore mediated by a D(2) receptor-dependent reduction in transmitter release, and a D(1) receptor-dependent increase in a K(+) conductance. This suppression of EPSPs may dampen the strength of sensory inputs during periods of elevated mesocortical dopamine activity.

Show MeSH
Related in: MedlinePlus