The contribution of single synapses to sensory representation in vivo

Abstract

The extent to which synaptic activity can signal a sensory stimulus limits the information available to a neuron. We determined the contribution of individual synapses to sensory representation by recording excitatory postsynaptic currents (EPSCs) in cerebellar granule cells during a time-varying, quantifiable vestibular stimulus. Vestibular-sensitive synapses faithfully reported direction and velocity, rather than position or acceleration of whole-body motion, via bidirectional modulation of EPSC frequency. The lack of short-term synaptic dynamics ensured a highly linear relationship between velocity and charge transfer, and as few as 100 synapses provided resolution approaching psychophysical limits. This indicates that highly accurate stimulus representation can be achieved by small networks and even within single neurons.

Fig. 1

Motion encoding at MF-GC synapses. (A) Simplified diagram of vestibular cerebellum with input from extrinsic MFs (eMF) or indirectly via intrinsic MFs (iMF) of local unipolar brush cells (UBC) (1, 26). The GC-Purkinje cell (P) pathway provides an inhibitory feedback loop to the vestibular nucleus. (B) Stimulus used to produce horizontal motion. (C) (Top) The positional command signal (green) and the recorded position (brown). (Middle) The position (green), velocity (black) and acceleration profiles (orange) obtained by differentiating the command signal. (Bottom) An example current trace of recorded EPSCs and a raster plot of EPSC onset times for 30 consecutive trials. (D) Trajectory plots for an example cell showing EPSC rate during motion (per 100 ms time bins, n = 30 trials) plotted against position, acceleration and velocity. (E) The evoked increase in EPSC frequency plotted against velocities recorded in the preferred direction for type 1 and type 2 responses. Linear fits through three to five average velocities (10°/s bins) are shown for each cell (n = 18). (Inset) A histogram of the slopes of each fit (gains). (F) Plot showing average EPSC frequencies recorded during baseline and for peak velocities in the preferred and non-preferred direction (range 35.2 to 37.7 °/s) for all cells. (Right) Example current traces showing asymmetry in EPSC frequency modulation. (G) Change in EPSC frequency from baseline rates plotted against velocity for all cells (n = 18). Error bars indicate SEM.

Fig. 2

Velocity is linearly represented by charge transfer. (A) Mean EPSC amplitude and weighted decays for EPSCs occurring during baseline and motion in the preferred direction (group 1: cells showing no change, P > 0.05, open circles, n = 13; group 2: showing a significant change, P < 0.05, solid circles; n = 5). (B) (Top to bottom) Velocity stimulus waveform, example current trace and EPSC amplitudes recorded from a group 1 cell plotted over time (n = 31 trials, 1,545 events). (C) Cumulative probability distributions for spontaneous and stimulus-evoked EPSC amplitudes recorded from the cell shown in (B). (Inset) The average EPSCs recorded during baseline (black) and motion in the preferred direction (gray). (D) Average EPSC traces for the same cell over 10°/s velocity bins, aligned on the time scale reporting the average preceding inter-EPSC interval for that velocity bin. Scale bar insert shows time scale for EPSC traces. (E) Population data for average EPSC amplitude recorded at different velocities (n = 13 cells). Data points reflect the mean values obtained from 10°/s velocity bins and are normalized to the average EPSC amplitude observed during baseline. Plot of change in charge transfer from baseline against EPSC frequency (F) and velocity (G) (all calculated over 100 ms bins) from a representative cell.

Fig. 3

Different GC inputs can be functionally distinct. (A) (Top to bottom) Velocity stimulus waveform, example current trace and EPSC amplitudes recorded from a group 2 cell plotted over time (n = 19 trials, 883 events). (B) Population data for group 2 cells showing the average amplitude for EPSCs recorded at different velocities (n = 5 cells). Error bars indicate SEM. (C) Cumulative probability distributions for spontaneous and stimulus-evoked EPSC amplitudes recorded from the cell shown in (A). (D) Peri-stimulus time histogram for the cell shown in (A), for which two populations of EPSCs could be distinguished. (E) On the basis of their amplitude distributions, inputs were separated (3/5 cells) and the amplitude for each input was plotted over a range of velocities. Small circles correspond to individual cells. Large circles are population averages (SEMs are plotted). (F) Average traces from the non-modulated (input 1) and modulated EPSC population (input 2) from the cell shown in (A). Average EPSC waveforms scaled to the same peak amplitude to highlight the distinct yet slow decay kinetics of both inputs.

Fig. 4

Real-time velocity representation by MF-GC synapses. (A) Example stimulus estimates based on a single trial for 1, 3, 8, 12, and 100 synapses. (B) Distribution of mean error (average absolute deviation between reconstruction and applied stimulus) for 100 repetitions for the indicated number of synapses. Gaussian fits (scaled) for all distributions are shown. (C) The reliability (standard deviation of the error) and accuracy (mean error) plotted against the number of synapses used for stimulus reconstructions.