Bursts modify electrical synaptic strength

Abstract

Changes in synaptic strength resulting from neuronal activity have been described in great detail for chemical synapses, but the relationship between natural forms of activity and the strength of electrical synapses had previously not been investigated. The thalamic reticular nucleus (TRN), a brain area rich in gap junctional (electrical) synapses, regulates cortical attention, initiates sleep spindles, and participates in shifts between states of arousal. Plasticity of electrical synapses in the TRN may be a key mechanism underlying these processes. Recently, we demonstrated a novel activity-dependent form of long-term depression of electrical synapses in the TRN (Haas et al., 2011). Here we provide an overview of those findings and discuss them in broader context. Because gap junctional proteins are widely expressed in the mammalian brain, modification of synaptic strength is likely to be a widespread and powerful mechanism at electrical synapses throughout the brain.

Figure 1

A) 60x IR image from patch recordings of a coupled pair of TRN neurons. B) Current injection into cell one (I₁) of a coupled pair drives a direct response in that cell (V₁) and a gap junction-relayed response in the second cell (V₂). The ratio of the voltage deflections is the coupling coefficient, cc. Scale bar 5 mV, 0.1 s. C) Mean gap junction conductance (G_C; see Methods) plotted against mean cc (dots). Open circles are a binned averages, with a slope of 7.9 (bin width 0.02; R² = 0.77, n = 313 pairs). The coefficient of variation, σ(G_C)/mean(G_C), was ~0.3 for all well-sampled bins. D) Directional cc (purpled, scaled by 10) and Gc (orange) for each pair; 1→2 represents coupling measured by current injection into cell 1, as in (B). E) Coupling asymmetry was quantified by distribution of ratios (cc₁₂/cc₂₁ and G₁₂/G₂₁). Asymmetry as measured by cc ratio had a mean of 1.6 ± 0.6 (purple, mean ± SD, n = 313 pairs) and by G_C ratio 1.2 ± 0.26 (orange; mean ± SD). Bin width was 0.05. With permission from [29].

Figure 2

A) Paired bursting was driven by simultaneous current injections into both cells of a coupled pair. Scale bars: 20 mV, 50 ms. Inset: zoom of paired burst event. B) Following 5 minutes of paired bursting at 2 Hz, cc depressed by 12.0 ± 3.6% and G_C depressed by 13.2 ± 1.8% (p < 0.05, n = 7 pairs). C) Average input resistance (R_in) and resting membrane potential (V_m) for the neurons summarized in (B). D) Measurements of coupling coefficients in one pair before and after activity pairing, measured as in Fig. 1B. Scale bar is 100 ms, 2.5 mV (coupled response, in black), 7.5 mV (direct response, in gray). E) Bursting was driven by injections of current into one cell of a coupled pair (black trace) while the other neuron was quiescent (grey trace). Scale bars: 20 mV, 50 ms. Inset: zoom of burst event and burstlet in quiescent neuron. F) Following 5 minutes of paired bursting at 2 Hz, cc depressed by 15.0 ± 3.4% and G_C depressed by 13.0 ± 2.3% (p < 0.05, n = 11 pairs). G) Average input resistance (R_in) and resting membrane potential (V_m) for the neurons summarized in (E). H) Measurements of coupling coefficients in one pair before and after activity pairing. Scale bar is 100 ms, 2.5 mV (coupled response, in black), 7.5 mV (direct response, in gray). With permission from [29].

Figure 3

A) Paired bursting was driven by simultaneous current injections into both cells of a coupled pair in the presence of 1μM TTX to block sodium spikes. Scale bars: 10 mV, 50 ms. Inset: zoom of paired burst event. B) Following 5 minutes of paired bursting at 2 Hz in TTX, cc depressed by 12.3 ± 3.2% and G_C depressed by 11.7 ± 2.6% (p < 0.05, n = 9 pairs). C) Average input resistance (R_in) and resting membrane potential (V_m) for the neurons summarized in (B). D) Burstlet amplitude during single-cell activity plotted against elapsed time during activity and normalized to final values. E) Bursting was driven by injections of current into one cell of a coupled pair (black trace) while the other neuron was quiescent (grey trace), also in TTX. Scale bars: 10 mV, 50 ms. Inset: zoom of burst event and burstlet in quiescent neuron. F) Following 5 minutes of paired bursting at 2 Hz, cc depressed by 6.5 ± 2.3% and G_C depressed by 6.0 ± 2.0% (p < 0.05, n = 11 pairs). G) Average input resistance (R_in) and resting membrane potential (V_m) for the neurons summarized in (E). H) Summary of changes in G_C for the four paradigms: paired bursting (2B), single-cell bursting (1B), paired bursting in TTX (2B + T), and single-cell bursting in TTX (1B + T). With permission from [29].

Figure 4

Gap junction-relayed activity before and after LTD. A₁) For one pair of neurons (cc₁₂ = 0.2, G₁₂ = 2.2 nS), spikes driven by current injection into cell 1 (grey traces, I₁) elicited a burst in cell 2 (blue traces, V₂). Scale bar 20 mV, 100 ms, 400 pA. A₂) After paired bursting resulting in LTD (ΔG_c = - 13%; Δcc₁₂ = -11%), the same stimulus and resulting spike train in cell 1 failed to elicit a burst in cell 2. B₁), B₂): Same paradigm as in (A) for a pair with initial cc₁₂ = 0.18 and G₁₂ = 1.3 nS, ΔG_c = - 9%; Δcc₁₂ = - 8%. Scale bar 20 mV, 100 ms, 400 pA. With permission from [29].

Figure 5

A) For activity in cell 1, cc₁₂ (blue) represents the ‘outbound’ coupling measured by current injection into cell 1, and cc₂₁ (green) represents ‘inbound’ coupling. B) Single-cell bursting in cell 1 with postsynaptic burstlets in cell 2. Scale bars: 20 mV, 50 ms. C) Inbound cc₂₁ before and after full bursts in cell 1. D) Outbound cc₁₂ before and after full bursts in cell 1. E) Ratios of directional cc (black filled circles; division of the changes in C divided by the changes in D for each pair) and G_C (open circles, p < 0.05 for both cc and G_C) following full bursts in cell 1, plotted against initial values. F) Bursts in cell 1 in 1 μM TTX. Scale bars: 20 mV, 50 ms. G) Inbound cc₂₁ before and after bursts in cell 1 in TTX. H) Outbound cc₁₂ before and after bursts in cell 1 in TTX. I) Ratios of directional cc (red filled squares; p = 0.6) and G_C (open squares; p = 0.76) following bursts in cell 1 in TTX, plotted against initial values. J) Model of an asymmetrical gap junction as two parallel branches. R_C represents the minimum conductance (maximum resistance) common to both sides of the gap junction and R_D represents additional, asymmetrical conductance in one direction. With permission from [29].