Intracellular correlates of stimulus-specific adaptation

Abstract

Stimulus-specific adaptation (SSA) is the reduction in response to a common stimulus that does not generalize, or only partially generalizes, to rare stimuli. SSA is strong and widespread in primary auditory cortex (A1) of rats, but is weak or absent in the main input station to A1, the ventral division of the medial geniculate body. To study SSA in A1, we recorded neural activity in A1 intracellularly using sharp electrodes. We studied the responses to tone pips of the same frequency in different contexts: as Standard and Deviants in Oddball sequences; in equiprobable sequences; in sequences consisting of rare tone presentations; and in sequences composed of many different frequencies, each of which was rare. SSA was found both in subthreshold membrane potential fluctuations and in spiking responses of A1 neurons. SSA for changes in frequency was large at a frequency difference of 44% between Standard and Deviant, and clearly present with tones separated by as little as 4%, near the behavioral frequency difference limen in rats. When using equivalent measures, SSA in spiking responses was generally larger than the SSA at the level of the membrane potential. This effect can be traced to the nonlinearity of the transformation between membrane potential to spikes. Using the responses to the same tone in different contexts made it possible to demonstrate that cortical SSA could not be fully explained by adaptation in narrow frequency channels, even at the level of the membrane potential. We conclude that local processing significantly contributes to the generation of cortical SSA.

Figure 1.

Effects of temporal context on the average membrane potential of a neuron in auditory cortex. This neuron did not have spiking responses. A, Top, A schematic representation of the Deviant f₂ Oddball sequence in which two tones were presented randomly. In 95% of the trials, the low tone (f₁ = 11.8 kHz) was presented and in the other 5% of the trials the high tone (f₂ = 17.1 kHz) was presented (Δf = 44%). Bottom, The average membrane potential in response to f₁ (blue) and f₂ (red). Gray background represents stimulus presentation time (30 ms). B, Top, A schematic representation of the Deviant f₁ Oddball sequence. The low tone (f₁) was presented in 5% of the trials, and the high tone (f₂) was presented in 95% of the trials. Bottom, Average membrane potential in response to f₁ (red) and f₂ (blue). C, Top, A schematic representation of the Equal control condition in which both f₁ and f₂ were presented in 50% of the trials. Bottom, Average membrane potential for both tones. D, Top, A schematic representation of the Diverse-narrow sequence in which the main two tones, f₁ and f₂, were presented among 18 other tones randomly. The ratio between adjacent tones was 3.37%. Bottom, Average response to f₁ and f₂ in this sequence. E, Top, A schematic representation of the Diverse-broad sequence in which the main two tones, f₁ and f₂, were presented among 10 other tones randomly. The spectral separation between each adjacent tone was Δf, the interval between f₁ and f₂ (44% here). Bottom, Average membrane potential in response to f₁ and f₂. F, Top, A schematic representation of the Deviant-alone sequence. Each tone was presented rarely as Deviant, while all other trials were silent. Bottom, Average responses to f₁ and f₂. G, Responses to f₁ tone in all conditions. H, Responses to f₂ tone in all conditions. I, Peak responses to f₁ and f₂ in all conditions. freqs, Frequencies.

Figure 2.

Responses of a typical neuron to f₁ and f₂ in all conditions for Δf = 4%, 10%, 21%, and 44% (color legend in bottom panel). Membrane potential responses were calculated after spike clipping. A, Average membrane potential responses. B, Smoothed PSTHs for the spiking responses of the same neuron. Same display and color conventions as in Figure 1.

Figure 3.

A, Population membrane potential responses (n = 55). B, Average normalized peak responses (bars) and a rough outline of their distributions (displayed as box plots) for the data as in A. The responses were normalized to the responses evoked in the Deviant-alone sequence of the each set. The number of responses in each bar is displayed below. C, SI₁ and SI₂ for each neuron plotted against each other. Red circle in Δf = 44% marks responses for the neuron in Figure 1. Blue circles in Δf = 21% and 4% mark the neuron that is shown in Figure 2. This neuron is not marked in 44% and 10% since its auditory responses were only marginally significant for one of the tones and therefore were not included in the corresponding scatter plots. D, Distribution of the CSI as a function of Δf.

Figure 4.

Population summary for spiking responses, using the same format as in Figure 3. A, Average population response for spiking activity represented as smoothed PSTHs. B, Average normalized peak responses (bars) and a rough outline of their distributions (displayed as box plots). The responses were normalized to the responses evoked in the Deviant-alone sequence of the each set. C, SI1 and SI2 for each neuron plotted against each other. Blue circles mark the neuron shown in Figure 2. D, Distribution of the CSI as a function of Δf.

Figure 5.

A, Membrane potential responses of a neuron in Standard (blue), Deviant (red), and Deviant-alone (green) conditions for three different ISIs (300, 700, and 1200 ms, averaged over f₁ and f₂, Δf = 44%). B, SI₁ and SI₂ for each neuron plotted against each other for all neurons tested with the three ISIs as in A (Δf = 44%). For ISI = 300, the plot is the same as in Figure 3 and is replotted for comparison. Blue circles mark the neuron that is shown in A. C, Distribution of the CSI for the different ISIs.

Figure 6.

Comparing SSA in membrane potential and spiking responses. A, CSI(V_m) responses against CSI(Spk) responses for all neurons that showed significant auditory responses for both. Blue circles mark the neuron that is presented in Figure 2. Red circles mark the examples used in Figure 7. B, ΔCSI [CSI(V_m) − CSI(Spk)] plotted against the baseline spiking rate of the neuron. Generally, a higher spontaneous rate corresponded to a larger ΔCSI (red lines − linear regression lines). C, CSI(V_m) plotted against the modified CSI(Spk) (see main text for details). Red and blue circles are as in A. D, ΔCSI [calculated for the modified CSI(spk)] plotted against the baseline spiking rate. At Δf = 20%, one dot is outside the limits of the plot (ΔCSI = −0.67; Spk/s = 1.6).

Figure 7.

Comparing SSA in membrane potential and spiking responses of two typical neurons. A1–D1, The first neuron is marked in Figure 6A with red circle above the main diagonal (Δf = 44%). A2–D2, The second neuron is marked in Figure 6A with a red circle below the main diagonal. A1, A2, Average membrane potential responses (left) and smoothed PSTHs for the spiking responses (right) to f₁ and f₂ in all six sequences. B1, B2, Peak responses for membrane potential (left) and spiking (right) responses. C1, C2, Comparing membrane potential (abscissa) and spiking (ordinate) responses to all sequences available for each neuron (C1, 12 responses, two frequencies with Δf = 44% in six sequences; C2, 36 responses for two frequencies, from 3 Δf values in 6 sequences) with a linear (dashed line) and exponential (full line) fits. D1, D2, Raster plots of the spiking responses (Δf = 44%).

Figure 8.

Single-trial analysis in one neuron (same neuron as in Fig. 1). A, Average responses (dark color traces) and single trials (light color traces) in Standard, Deviant, and Deviant-alone conditions for f₁ (top) and f₂ (bottom). All 25 trials of the Deviant and Deviant-alone conditions, and 25 randomly selected trials of the Standard condition are displayed. Stimulus duration (30 ms) is marked as a horizontal colored line at the bottom. B, Membrane potential values at the peak response after tone onset in all trials (ordinate) plotted against baseline membrane potential (abscissa) for all trials of the three sequences in A (y-axis is the same as in A). Histograms show distribution of the peak responses.

Figure 9.

A, Membrane potential values at the peak response after tone onset in all trials (ordinate) plotted against baseline membrane potential (abscissa) for all trials from six neurons that did not spike. Only f₁ responses are shown. Dark blue, First Standards following a Deviant; light blue, all other Standards; red, Deviants. B, Average peak responses to the last Standard before Deviant (light blue), Deviant (red), and the first eight Standards following a Deviant as a function of their sequential positions. The response to the first Standard after a deviant is marked in dark blue. Data are from all neurons that did not spike (n = 17). Responses were normalized by subtracting the average baseline for each neuron. Error bars are SEs. C, Same as B, for the average normalized baseline membrane potential at stimulus onset. Baseline was normalized by subtraction of the average baseline, across all trials, for each neuron.

Figure 10.

Model responses (ordinate) plotted against the measured responses (abscissa) for all Δf conditions. A, Membrane potential responses. B, Spiking responses.

Figure 11.

A, Distributions of the ratio of the ε² and the sum of the se², shown separately for V_m and spikes. The weighted F(n,n) distribution is plotted in continuous lines. The vertical dotted line indicates the 95% critical point of the expected distribution. B, Scatter plot of membrane potential fit ratios (abscissa) against spike fit ratios (ordinate). C, Distributions of the half-width of the adaptation channel (σ) shown separately for V_m and spikes. D, Comparison of σ estimated from membrane potential responses (abscissa) and spiking responses (ordinate).

Figure 12.

Comparison between Deviant and Diverse-broad responses in real neurons and in the modeled responses. A, Deviant responses plotted against Diverse-broad responses for individual neurons (Δf = 44%). Left, Observed responses; right, modeled responses. B, Red, Comparing responses to Deviants as predicted from the full model and as predicted from the model with the Deviant responses left out of the training set. The box plots display the distributions of the differences between the two, the large majority of which are positive. Thus, Deviant predictions generally based on all other data are too small. Yellow, Same for the Diverse-broad responses. Here the differences are mostly negative, showing that the predictions of the responses to the Diverse-broad condition, based on all other responses, are generally too large. Left, For membrane potential data (V_m); right, for spike data; both for Δf = 44%.