Dynamic properties of corticogeniculate excitatory transmission in the rat dorsal lateral geniculate nucleus in vitro

Abstract

The feedback excitation from the primary visual cortex to principal cells in the dorsal lateral geniculate nucleus (dLGN) is markedly enhanced with firing frequency. This property presumably reflects the ample short-term plasticity at the corticogeniculate synapse. The present study aims to explore corticogeniculate excitatory postsynaptic currents (EPSCs) evoked by brief trains of stimulation with whole-cell patch-clamp recordings in dLGN slices from DA-HAN rats. The EPSCs rapidly increased in amplitude with the first two or three impulses followed by a more gradual growth. A double exponential function with time constants 39 and 450 ms empirically described the growth for 5-25Hz trains. For lower train frequencies (down to 1Hz) a third component with time constant 4.8 s had to be included. The different time constants are suggested to represent fast and slow components of facilitation and augmentation. The time constant of the fast component changed with the extracellular calcium ion concentration as expected for a facilitation mechanism involving an endogenous calcium buffer that is more efficiently saturated with larger calcium influx. Concerning the function of the corticogeniculate feedback pathway, the different components of short-term plasticity interacted to increase EPSC amplitudes on a linear scale to firing frequency in the physiological range. This property makes the corticogeniculate synapse well suited to function as a neuronal amplifier that enhances the thalamic transfer of visual information to the cortex.

Figure 1. Increase in amplitude of corticogeniculate EPSCs with repetitive stimulation

A, averaged EPSCs evoked by stimulation of corticogeniculate axons in the optic radiation by a train of 10 pulses (3 V) at 25Hz. Stimulation artefacts are truncated. B, development of facilitation (EPSC_n/EPSC₁) at 25Hz; mean ±s.e.m. for 30 cells. The data points could be empirically described by the sum of two exponential functions (f(t) = F_ss−K₁× exp(−t/τ₁) −K₂× exp(−t/τ₂)). The continuous line is a least-sum-of-squares fit providing time constants τ₁= 39 ms and τ₂= 450 ms. The dotted line is a linear regression for EPSC₃− EPSC₁₀ with r²= 0.98. C, EPSC₁ (thin black line), EPSC₃ (thick grey line) and EPSC₁₀ (dotted grey line) from record in A, scaled in amplitude and overlaid at the same time scale. Note that the waveforms are similar with a slightly increased duration of EPSC₁₀.

Figure 2. Prolonged train stimulation with different degrees of recruitment

A, compound EPSCs evoked at 2 different intensities (2.5 V upper trace; 3.5 V lower trace) to recruit different numbers of corticogeniculate synapses at the same dLGN cell. Averages of 10 (upper trace) and 5 records (lower trace). Stimulation artefacts are truncated for clarity. B, facilitation of EPSCs over time for the trains in A; 2.5 V (□) and 3.5 V (▪); means ±s.e.m. Note the lack of depression and that the facilitation is similar despite a fourfold increase in EPSC amplitudes.

Figure 3. Corticogeniculate EPSC facilitation with 5–25Hz trains

A, facilitation of EPSCs over time in trains at 25 (▪), 16.7 (□), 10 (⊠) and 5Hz (). Lines are least-sum-of-squares fits of a double exponential function as in Fig. 1 with the same time constants τ₁ = 39 ms and τ₂ = 450 ms. B, diagram comparing EPSC amplitudes at different points in time (t) for 5–25Hz trains. Data points are EPSC amplitude at, or immediately preceding t = 0.2 or 0.4 s. Continuous lines are linear regressions with Δy_{t = 0.2s}= 0.23 and Δy_{t = 0.4s}= 0.25. The dotted line is the theoretical F_ss (×) regression line with Δy_{t =∞}= 0.26 at the theoretical point in time t=∞. Other markers are the same as in A. Data points in A and B are average values ±s.e.m. from the same 10 cells.

Figure 4. EPSCs growth with 1–50Hz trains

A, growth in EPSC size compared to position in the train (n= sequential pulse number) for 25 (▪), 16.7 (□), 10 (⊠), 5 (), 2 () and 1Hz (). Lines are exponential functions with time constants (τ₁= 39 ms, τ₂= 0.45 s and τ₃= 4.8 s) transformed from the temporal domain to stimulus number (n). B, EPSC_n/EPSC₁ at 50 (□) and 25Hz (▪) over time. C, contribution of each exponential component in curve fits in A plotted against frequency (K₁, ⋄; K₂, ♦; K₃, ). Continuous lines are curve fits; for K₁ a linear regression between 2 and 25Hz (Δy_K1= 0.20 versus frequency), for K₂ a linear regression for data between 5 and 25Hz (Δy_K2= 0.07) and for K₃ an exponential decay. Dotted line is a regression line for K₂+K₃ (×; Δy_K2+K3= 0.06). Further details in the text. Average values ±s.e.m. from the same 10 cells as in Fig. 2.

Figure 5. Effect of changes in [Ca²⁺]_o on amplitude and facilitation of corticogeniculate EPSCs

A, averaged traces for 25Hz trains (2.5 V) at different [Ca²⁺]_o; 10 records in 1 cell. Stimulation artefacts are truncated. B, average EPSC amplitudes (±s.e.m.) plotted against [Ca²⁺]_o on a logarithmic scale. ○, EPSC₁; •, EPSC₂; ⊗, EPSC₇. Lines are least-sum-of-squares fits of Hill functions, f([Ca²⁺]_o) = EPSC_max×[Ca²⁺]_o^N/(K_½^N+[Ca²⁺]_o^N). Exponential (N) was 1.6 for EPSC₁, 2.6 for EPSC₂ and 2.7 for EPSC₇. Binding constants (K_½) were 8.3, 2.5 and 1.5, respectively. C, facilitation relative to EPSC₁ for EPSC₂ (▪) and EPSC₇ (squares with cross) versus[Ca²⁺]_o.

Figure 6. Train stimulation at 1.0, 2.0 and 3.0mm[Ca²⁺]_o

A, EPSC amplitudes at [Ca²⁺]_o 1.0 (⊗), 2.0 (•) and 3.0mm (○). Normalized to EPSC₁ at 2.0mm. Lines are double exponential curve fits with τ₂= 450 at all [Ca²⁺]_o, while τ₁ was more rapid with increasing [Ca²⁺]_o as shown in inset. B, facilitation of EPSCs at the different [Ca²⁺]_o in A. Lines are double exponential functions as in A. Train stimulation at 25Hz. All points are averages ±s.e.m. from 6 cells.

Figure 7. The corticogeniculate neuronal amplifier increases the dynamic range of dLGN cell firing in response to visual stimuli

A, schematic illustration of excitatory input to principal cells in the dorsal lateral geniculate nucleus (dLGN). Glutamatergic synapses carry information from the retina with axons in the optic tract (OT) and feedback from cortex with axons in the optic radiation (OR). Modulatory input (M, shown in grey) may be from the brainstem. B, model input–output relationships for a principal cell for different mechanisms that would increase the relay to cortex. Dashed line illustrates basal conditions in the spike-firing mode where low threshold calcium currents are inactive. A further depolarization mediated by a modulatory input would increase the output frequency without a change in the dynamic range (grey continuous line). The corticogeniculate neuronal amplifier would, when activated, increase the frequency span of the output by adding progressively more feedback excitation per impulse at higher frequencies (black continuous line).