D1 and D2 receptor-mediated dopaminergic modulation of visual responses in cat dorsal lateral geniculate nucleus - PubMed (original) (raw)

D1 and D2 receptor-mediated dopaminergic modulation of visual responses in cat dorsal lateral geniculate nucleus

Yongqiang Zhao et al. J Physiol. 2002.

Abstract

The modulatory effects of dopamine (DA) on the visual responses of relay cells of the dorsal aspect of cat lateral geniculate nucleus (dLGN) were tested using local micro-iontophoretic application of DA and application of the receptor-specific agonists SKF38393 (SKF, D1/D5) and quinpirole (QUIN, D2/D3/D4) in the anaesthetized alcuronium-treated cat. The effects of DA and QUIN were clearly dose-dependent: small amounts caused a weak and transient facilitation of visual activity (10-30% increase) preferentially in Y-type relay cells, which changed to a moderate reduction of visual responses when the dose was increased (50%, maximal 70%). The effect of SKF was mainly suppressive and increased with the amount of drug applied (up to 90% reduction). The selective antagonists SCH23390 (SCH, D1) and sulpiride (SULP, D2) reduced the effects of co-applied DA agonists. We found little evidence for a specific dopaminergic modulation of the surround inhibition (stimulus-driven lateral inhibition) although DA slightly facilitated the transmission of weak signals (small stimuli). Nevertheless, some dopaminergic effects seem to be mediated via inhibitory interneurons regulating the strength of sustained or recurrent inhibition. Application of DA agonists during blockade of GABA(A) receptors indicates a direct suppression of relay cells via D1 receptors, an excitation of relay cells via D2 receptors and--with increasing amounts of D2 agonist--probably also an excitation of inhibitory interneurons, which results in an indirect inhibition of dLGN relay cells (predominantly of the X-type). The results are discussed in relation to the impairment of visual functions in Parkinson's disease.

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Figures

Figure 1

Figure 1. Single-unit responses to visual stimulation and application of dopaminergic agents

A, dopamine (DA) application with different ejection currents (nA) shows slight facilitation with 10 nA and inhibition with 20–40 nA. B, dose-dependent inhibition of visual responses was seen with the D1 agonist SKF; partial compensation of the inhibitory effect was observed during co-application of the D1 antagonist SCH. C, facilitation (10 nA) and inhibition (20–30 nA) of visual activity caused by the D2 receptor agonist QUIN; inhibition was eliminated during co-application of the D2 antagonist SULP. An X-off cell is shown in A, an X-on cell in B and an X-off cell in C. Peri-stimulus-time histograms were calculated from 50 repetitions of the same stimulus (stimulus protocol below the histograms). Time labels to the left of the histograms indicate the onset time of each record relative to the onset of the control record.

Figure 2

Figure 2. Dose-dependent DA effect on the peak and tonic responses of Y- and X-cells to spot stimuli of different sizes

The bar histograms in A and B show mean (absolute) response levels and standard errors of the mean during control records, records with 10, 20, 30 and 40 nA dopamine (DA) application and recoveries. * Significantly different from control responses (P < 0.05, Student's paired t test, six Y-cells, six X-cells). The histograms in C show changes in Y-cell responses relative to control levels (percentage). Spot sizes (1–6) were chosen relative to receptive field size (see inset lower right and text).

Figure 3

Figure 3. Dose-dependent effect of the D1 receptor agonist SKF on the peak and tonic responses of Y- and X-cells to spot stimuli of different sizes

The bar histograms in A and B show mean (absolute) response levels and standard errors of the mean during control records, records with 10, 20, 30 and 40 nA SKF application and recoveries. The data are averaged from four Y-cells and five X-cells; otherwise the same conventions are used as in Fig. 2.

Figure 5

Figure 5. Drug-induced changes in response levels are largely proportional to absolute control response levels

Relationship between control response levels to different spot sizes and the effects of DA, SKF and QUIN on visual responses of Y- and X-cells (DA: six Y, six X; SKF: four Y, five X; QUIN: seven Y, five X). Mean response levels during control records are plotted in absolute terms while response levels obtained during drug application are plotted as differences from control responses (drug record level minus control record level). Data were derived from the histograms shown in Figs 2–4. Error bars were omitted for clarity.

Figure 4

Figure 4. Dose-dependent effect of the D2 receptor agonist QUIN on the peak and tonic responses of Y- and X-cells to spot stimuli of different sizes

The bar histograms in A and B show mean (absolute) response levels and standard errors of the mean during control records, records with 10, 20, 30 and 40 nA QUIN application and recoveries. Averaged data from seven Y-cells and five X-cells. Otherwise same conventions as in Fig. 2.

Figure 6

Figure 6. Effect of DA on X- and Y-cells with and without blockade of GABAA inhibition by co-application of bicuculline methiodide (BICU)

A shows an example of a single-unit response (X-on cell). Peri-stimulus-time histograms were calculated from 50 repetitions of the same stimulus (bright spot of size 3). Time labels to the left of the histograms indicate the onset time of each record relative to the onset of the control record. The bar diagrams (B and C) summarize the results obtained from 13 X-cells and 15 Y-cells. Asterisks label response levels during co-application of BICU and DA which are statistically significantly different from those during sole BICU application (P < 0.05, Student's t test). The contribution of [backround] inhibition was tested with sole BICU application.

Figure 7

Figure 7. Effect of SKF on X- and Y-cells with and without blockade of GABAA inhibition by co-application of BICU

Single-unit example in A (X-on cell, bright spot size 4), averaged data of 12 Y-cells and five X-cells in B and C. Otherwise, the same conventions are used as in Fig. 6.

Figure 8

Figure 8. Effect of QUIN on X- and Y-cells with and without blockade of GABAA inhibition by co-application of BICU

Single-unit example in A (X-on cell, bright spot size 3), averaged data of five Y-cells and seven X-cells in B and C. Otherwise, the same conventions are used as in Fig. 6.

Figure 9

Figure 9. Efficiency of the DA receptor antagonists SCH (D1) and SULP (D2) in blocking the action of the receptor agonists SKF and QUIN

QUIN was tested with two different ejection currents (10 and 30 nA) because of opposite effects on response levels. *Mean response levels statistically different from control levels (P < 0.05, Student's t test). † Mean response level statistically different (P < 0.05) from that during sole agonist application. Responses obtained from X- and Y-cells evoked by different spot sizes were pooled in this case.

Figure 10

Figure 10. Summary of dopaminergic input systems to cat dLGN

Sketch of the simplified circuitry of cat dLGN and the possible cells and receptor types targeted by the dopaminergic innervation. For explanation see Discussion.

Figure 11

Figure 11. Response dynamics of X- and Y-cells during continuous QUIN application

The mean tonic activity of five X- and five Y-cells is plotted over time after onset of QUIN application with 10–20 nA. The curves were slightly smoothed by calculating sliding means from three successive responses. The responses were normalized to the mean of the three first response levels, which were set to 0 on the graph. Continuous lines show Y-cell activity, dashed lines that for the X-cells. The grey lines show overall means for X- and Y-cells. Regression lines have also been added.

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