Cellular mechanisms of temporal sensitivity in visual cortex neurons - PubMed (original) (raw)
Comparative Study
Cellular mechanisms of temporal sensitivity in visual cortex neurons
Jessica A Cardin et al. J Neurosci. 2010.
Abstract
The ability of cortical neurons to accurately encode the temporal pattern of their inputs has important consequences for cortical function and perceptual acuity. Here we identify cellular mechanisms underlying the sensitivity of cortical neurons to the timing of sensory-evoked synaptic inputs. We find that temporally coincident inputs to layer 4 neurons in primary visual cortex evoke an increase in spike precision and supralinear spike summation. Underlying this nonlinear summation are changes in the evoked excitatory conductance and the associated membrane potential response, and a lengthening of the window between excitation and inhibition. Furthermore, fast-spiking inhibitory interneurons in layer 4 exhibit a shorter window of temporal sensitivity compared with excitatory neurons. In contrast to the enhanced response to synchronous inputs by layer 4 neurons, sensory input integration in downstream cortical layers is more linear and less sensitive to timing. Neurons in the input layer of cortex are thus uniquely optimized to detect and encode synchronous sensory-evoked inputs.
Figures
Figure 1.
Comparison of one-dimensional and two-dimensional receptive field maps. The receptive field of this simple layer 4 regular-spiking cell was first mapped using a Gaussian-filtered noise stimulus, which generated a detailed two-dimensional map (left). The receptive field was then mapped by presenting individual optimally oriented bright and dark bars in 16 positions covering the same area of visual space, generating the corresponding one-dimensional map (right). The two sets of stimulus responses identified the same set of receptive field subregions, indicating good correspondence between the one- and two-dimensional maps.
Figure 2.
Temporally coincident stimuli in the receptive field evoke supralinear spike output and changes in spike timing. A, Optimally oriented bright and dark bars were flashed (128 ms) in 16 positions across the receptive field of a layer 4 simple cell, generating a one-dimensional map. Bar positions A and B were chosen as sites in two discrete receptive field subregions that evoked strong bright and dark responses, respectively. B, Bars A and B each evoked spike output when briefly presented alone (16 ms), but evoked more spikes with a narrower temporal distribution when presented simultaneously. Each example is generated from 10 overlaid traces. C, PSTHs from 30 presentations of A and B alone. D, PSTHs of recorded responses to 30 presentations of A and B together presented at varying interstimulus intervals (black) were compared to predicted PSTHs calculated as the linear sum of the responses to A and B alone (gray). The summed responses were measured within a window bounded by the beginning of the response at an ISI of 0 ms and the end of the responses to A and B alone (dashed line). E, Distributions of the first spike evoked by each of 30 presentations of A and B as a function of their temporal asynchrony.
Figure 3.
Temporally coincident stimuli result in nonlinear summation of spike responses in layer 4. A, For each cell (n = 19 layer 4 simple cells), the number of spikes on each stimulus trial was compared to the expected spikes per trial, assuming linear summation. Within an ISI of 0 to 16 ms, coincident stimuli evoked significantly more spikes per trial than expected. Beyond 16 ms, responses to paired stimuli were linear. B, Similarly, the mean instantaneous firing rate was significantly supralinear within the same 16 ms time window. C, Median spike latency was significantly advanced in response to stimuli at short intervals. D, Precision of the timing of the first evoked spike on each trial, measured as the median interquartile range of spike times (IQR), was significantly increased at short interstimulus intervals. Dashed lines indicate mean precision in response to A and B alone. Error bars indicate SEM. *p < 0.05; **p < 0.01.
Figure 4.
Sublinear summation of synaptic potentials underlying supralinear spike output. A, Membrane potential responses to bars A and B in an example layer 4 simple cell. Spikes have been removed. B, Average PSPs in response to A and B together at varying intervals (black) compared to the predicted responses calculated as the linear sum of the responses to A and B alone (dashed). At short intervals, the observed responses were smaller in amplitude than the expected responses and were advanced in time. C, Expanded traces of the observed responses to A and B individually and A and B together at an ISI of 0 ms are shown with the linear prediction of A and B (dashed). The response to A and B together was larger than the responses to either A or B alone. D, Expanded traces from the box in B of the observed (black) and expected (dashed) responses to A and B together at an ISI of 0 ms. The membrane potential trajectory (_dV_m/dt) of the observed response was faster than that of the expected response.
Figure 5.
Coincident stimuli evoke sublinear _V_m summation and faster membrane potential trajectory. A, For each cell (n = 19 layer 4 simple cells), average observed _V_m responses were compared to expected responses, assuming linear summation. _V_m summation was significantly sublinear at short ISIs, and became linear at ISIs of >16 ms (filled circles). This sublinearity is partially attributable to the presence of spikes, as cells recorded with QX-314 demonstrated decreased, but still significantly sublinear, summation (n = 9 layer 4 simple cells; open circles). B, Timing of the peak of the evoked PSP was significantly advanced in responses to paired stimuli at short intervals. C, The _dV_m/dt of the _V_m responses to coincident stimuli within a short window was significantly increased (filled circles). This increase was eliminated in the presence of QX-314 (open circles). The dashed line denotes mean _dV_m/dt in response to bars A and B presented individually. The dotted line denotes mean _dV_m/dt in response to A and B in the presence of QX-314. D, Apparent spike threshold of the first evoked spike in each trial was significantly decreased in response to temporally coincident stimuli. Error bars indicate SEM. *p < 0.05; **p < 0.01.
Figure 6.
Fast-spiking inhibitory interneurons have a shorter window for temporal sensitivity. The population of layer 4 simple cells was divided into RS, putative excitatory neurons and FS, putative inhibitory interneurons. A, In both cell types, coincident inputs at an ISI of 0 ms evoked a sublinear summation of _V_m responses. However, summation in FS cells returned to linearity at all other interstimulus intervals, whereas RS cells showed significant nonlinearity in response to all inputs at ≤16 ms intervals. B, Similarly, FS cells showed a much narrower window for supralinear summation of spike responses. FS cells demonstrated supralinear summation of spike responses only at very short ISIs, whereas RS cells showed supralinearity over a much wider range. Single asterisks denote significant difference between the degree of nonlinearity between RS and FS cell responses at each time interval (p < 0.05). C, FS cells showed an increase in _dV_m/dt only in response to paired bars at an ISI of 0 ms, whereas RS cells showed increases in _dV_m/dt at ISIs of ≤16 ms. Dotted and dashed lines indicate FS and RS _dV_m/dt values in response to single flashed bars, respectively. Error bars indicate SEM.
Figure 7.
Visual stimulus synchrony changes the relative timing of evoked excitatory and inhibitory conductances. A, Estimates of the excitatory (green) and inhibitory (black) conductances underlying the _V_m responses to bars A and B alone. These data were acquired using QX-314 in the pipette. B, Estimates of the excitatory and inhibitory conductances evoked by A and B together at an ISI of 0 ms (solid lines) and predicted conductances, assuming linear summation of the responses to A and B alone. Squares represent the time of the peak of each conductance. The onset and peak of the observed excitatory, but not inhibitory, conductance occurred earlier than predicted, as shown by the vertical arrows. This generated a prolonged period of excitatory dominance before the onset of the subsequent inhibition. C, Reversal potential (black) and input resistance (gray) during the _V_m response (blue) of this cell to A and B together at an ISI of 0 ms. D, Excitation–inhibition (E–I) delay, measured as the time between the peaks of the excitatory and inhibitory conductances, was significantly longer at ISIs of 0 and 8 ms than in response to A or B alone. At longer ISIs, the E–I delay decreased to baseline levels. Error bars indicate SEM. *p < 0.05; **p < 0.01.
Figure 8.
Sensitivity to coincident inputs decreases in downstream cortical layers. A, Layer 4 cells (dark blue) showed the largest spike output supralinearity in response to coincident stimuli. Layer 2/3 cells (light blue) showed less summation nonlinearity, and layer 5/6 cell (green) responses summed linearly regardless of stimulus timing. B, Similarly, the shift in timing of the spike response to coincident stimuli was most advanced in layer 4, and much less so in downstream layers. C, Precision of the timing of the first evoked spike in layer 4 cells was significantly increased in response to coincident stimuli, but less so in layers 2/3 or 5/6. Overall, spike precision was greatest in layer 4, and least in layer 2/3. In each case, statistical significance is shown here only for comparisons between layer 4 and downstream layers at an ISI of 0 ms. *p < 0.05; **p < 0.01.
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References
- Abeles M, Bergman H, Margalit E, Vaadia E. Spatiotemporal firing patterns in the frontal cortex of behaving monkeys. J Neurophysiol. 1993;70:1629–1638. - PubMed
- Alonso JM, Usrey WM, Reid RC. Precisely correlated firing in cells of the lateral geniculate nucleus. Nature. 1996;383:815–819. - PubMed
- Anderson JS, Carandini M, Ferster D. Orientation tuning of input conductance, excitation, and inhibition in cat primary visual cortex. J Neurophysiol. 2000;84:909–926. - PubMed
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