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The Journal of Neurophysiology Vol. 80 No. 6 December 1998, pp. 3005-3020
Copyright ©1998 by the American Physiological Society
1 Department of Neurobiology, University of Pittsburgh School of Medicine, Pittsburgh 15261; and 2 Center for the Neural Basis of Cognition, Pittsburgh, Pennsylvania 15213
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ABSTRACT |
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 Abstract
 Introduction
Methods
Results
Discussion
References
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Humphrey, Allen L., Alan B. Saul, and Jordan C. Feidler. Strobe rearing prevents the convergence of inputs with different response timings onto area 17 simple cells. J. Neurophysiol. 80: 3005-3020, 1998. The preceding paper showed that the loss of direction selectivity in simple cells induced by strobe rearing reflects the elimination of spatially ordered response timing differences across the receptive field that underlie spatiotemporal (S-T) inseparability. Here we addressed whether these changes reflected an elimination of certain timings or an alteration in how timings were associated in single cells. Timing in receptive fields was measured using stationary bars undergoing sinusoidal luminance modulation at different temporal frequencies (0.5-6 Hz). For each bar position, response phase versus temporal frequency data were fit by a line to obtain two measures: absolute phase and latency. In normal cats, many individual simple cells display a wide range of timings; in layer 4, the mean range for absolute phase and latency was 0.21 cycles and 39 ms, respectively. Strobe rearing compressed the mean timing ranges in single cells, to 0.08 cycles and 31 ms, respectively, and this compression accounted for the loss of inseparability. A similar compression was measured in layer 6 cells. In contrast, the range of timing values across the simple-cell population was relatively normal. Single cells merely sampled narrower than normal regions of the timing space. We sought to understand these cortical changes in terms of how inputs from the lateral geniculate nucleus (LGN) may have been affected by strobe rearing. In normal cats, a wide range of absolute phase and latency values exists among lagged and nonlagged LGN cells, and these thalamic timings account for most of the cortical timings. Also, S-T inseparability in many simple cells can be attributed to the convergence of lagged and/or nonlagged inputs. Strobe rearing did not change the sampling of lagged and nonlagged cells, and the geniculate timings continued to account for most of the cortical timings. However, strobe rearing virtually eliminated cortical receptive fields with mixed lagged and nonlagged timing, and it compressed the timing range in cells dominated by one or the other geniculate type. Thus strobe rearing did not eliminate certain timings in LGN or cortex, but prevented the convergence of different timings on single cells. To account for these results, we propose a developmental model in which strobe stimulation alters the correlational structure of inputs based on their response timing. Only inputs with similar timing become associated on single cortical cells, and this produces S-T separable receptive fields that lack the ability to confer a preferred direction of motion.
The preceding paper (Humphrey and Saul 1998 Cortical data were obtained using the strobe-reared and normal cats described in the preceding paper (Humphrey and Saul 1998 Response timing
Methods for studying response timing in LGN and cortex are described elsewhere (Humphrey and Saul 1998
Identifying cells
Simple cells were identified as previously described (Humphrey and Saul 1998 Statistics
Most comparisons between means were based on the t-test (Winer 1962 Examples of response timing in simple cells
Figure 1 illustrates response timings in three representative simple cells from normal and strobe-reared cats. For each cell, a set of PSTHs obtained at one of several tested temporal frequencies shows the S-T structure of the receptive field (Fig. 1, A, C, and E). For each stimulus position we plotted the fundamental response temporal phase versus stimulus temporal frequency and fit the points with a line. Figure 1, B, D, and F, shows data for stimulus positions with reliable timings. Latency and absolute phase values derived from these fits are indicated in parentheses.
Range of timings in cortical receptive fields: single cell versus population data
The differences between cells in Fig. 1 that were or were not direction selective epitomize the key effect of strobe rearing: it produced a compression in the range of response timings in individual receptive fields. For example, the inseparable field in A, from a normal cat, resulted from latency and absolute phase values that spanned a range of 40 ms and 0.35 cycles, respectively. In contrast, the range for the separable field in E, from a strobe-reared cat, was narrower: 29 ms and 0.03 cycles.
Alterations in geniculocortical relationships?
The fact that strobe rearing greatly narrowed the range of timings in single receptive fields suggests that it altered cells' inputs. The LGN is a major source of inputs to cortex, and the afferent timings may be relayed to cortical cells either directly (Reid and Alonso 1995 Cell types and response timings in the LGN
We recorded from 52 cells in the geniculate A-laminae of strobe-reared cats. Most receptive fields were within 10° of the area centralis. The physiological class of all but two units could be easily identified. The exceptions were one cell with mixed X and Y properties and one that was suppressed by bright and dark stimuli. Mixed cells exist in normal cats (Wilson et al. 1976
OTHER RESPONSE PROPERTIES.
We noted previously (Humphrey and Saul 1998 Effects of strobe rearing on the convergence of geniculate-like timings in individual simple cells
Having determined that strobe rearing did not affect lagged and nonlagged LGN cells, we pursued the hypothesis that it interfered with the linking of their timings in cortical cells. Indeed, Fig. 3 suggests that this was the case. In normal layer 4, the range of absolute phase values in many direction-selective receptive fields reflected phase leads and lags (Fig. 3A). After strobe rearing receptive fields displayed either phase leads or lags, but rarely both (Fig. 3B). The main exceptions were the few direction-selective cells, which displayed both types of timings. To further address the linkage hypothesis, we classified cortical cells based on their geniculate-like timings, using both absolute phase and latency to identify timing type.
NORMAL CATS.
The sample from normal cats consisted of 31 cells from a previous study (Fig. 15 of Saul and Humphrey 1992a STROBE-REARED CATS.
Of 54 cells in strobe-reared cats, 7 (13%) were predominantly lagged, 46 (85%) were predominantly nonlagged, and 1 (2%) was mixed (Fig. 8B). Strobe rearing thus had no effect on the sampling of predominantly lagged cells but led to a slight increase in the frequency of predominantly nonlagged cells (i.e., 65 to 85%) and a marked decrease in mixed cells (22 to 2%).
Laminar locations of timing types
We previously showed that simple cells with lagged- and/or nonlagged-like timing have characteristic laminar distributions in area 17 (Saul and Humphrey 1992a In the companion paper (Humphrey and Saul 1998 Strobe rearing and LGN development
Strobe rearing had no major effect on neurons in the A-laminae of the LGN. Lagged and nonlagged X- and Y-cells were sampled in normal frequencies, and their temporal and spatial response properties were normal. Thus geniculate, and presumably retinal, circuits appear to have developed appropriately despite the altered temporal pattern of stimulation. Physiological and anatomic evidence indicates that lagged and nonlagged responses are produced by different circuits. Lagged cells receive their excitatory drive from retinal cells that have nonlagged-like discharge profiles (Mastronarde 1987a Sources of cortical timings in layer 4
Our working assumption is that lagged and nonlagged cells provide the timings that underlie S-T inseparable receptive-field structure and direction selectivity in cat area 17. Here we briefly review evidence from normal animals that supports this assumption. We next consider some alternative models for the origin of cortical timings. Finally, we consider the strobe rearing results from a geniculocortical perspective. We will focus on layer 4 because the relationship between S-T structure and direction selectivity is clearest there.
Directional mechanisms in layer 6
Our data provide few insights into directional mechanisms in layer 6 or the loss of directional tuning there following strobe rearing. We have shown in normal cats that "first-order" S-T maps derived from responses to counterphasing gratings (Murthy et al. 1998 Model to account for the effects of strobe rearing
Here we propose a mechanism for how strobe rearing changes receptive-field structure. We assume that, during development, inputs with different response timings form connections with a common cortical cell via a competitive, self-organizing process that strengthens synaptic connections of well-correlated inputs. Such a Hebb-type process has been shown to account for the development of receptive-field spatial structure and orientation selectivity (Miller 1990
INTRODUCTION
Abstract
Introduction
Methods
Results
Discussion
References
) showed that strobe rearing causes a loss of direction-selective responses in simple cells of area 17 by altering the space-time structure of their receptive fields. In normal cats, most direction-selective cells display varying degrees of spatiotemporal (S-T) inseparability. The gradual timing shifts across their receptive fields confer a preferred direction of motion (Jagadeesh et al. 1997; McLean et al. 1994; Reid et al. 1991). After strobe rearing, all cells lacking directional tuning had S-T separable receptive fields. The absence of timing gradients in these receptive fields appears to have greatly affected the ability of cells to generate differential responses to opposite directions of motion.
). Latency reflects conduction delays and integrative processes that occur between the critical stimulus event and the cell's excitatory response. It contributes most to response phase at higher temporal frequencies (>2 Hz). A broad range of absolute phase and latency values is observed in the simple-cell population of cortex (Saul and Humphrey 1992a). Within individual receptive fields, the spatial distribution of these timings determines S-T structure.
). The two groups differ in their temporal response properties; lagged cells display absolute phase delays and long latencies relative to nonlagged cells (Saul and Humphrey 1990). In cortex, their characteristic timings are observable in simple cells, particularly in layer 4. Gradual shifts in response timing across S-T inseparable receptive fields there can be accounted for by converging lagged and nonlagged inputs with spatially shifted receptive fields (Saul and Humphrey 1992a). Other inseparable cells may exhibit a range of timings that are purely lagged- or nonlagged-like.
) or to stimuli presented briefly (e.g., <10 ms duration; unpublished observations). Strobe rearing might interfere with the development of lagged cells or with their ability to form connections in cortex. Alternatively, the different LGN cell types might develop normally but fail to converge on common cortical cells. Still another possibility is that strobe rearing might change the timing properties of all geniculate and cortical cells, producing timing distributions markedly different from normal.
) that showed strobe-induced elimination of timing differences in simple-cell receptive fields, we documented the degree of timing compression. This showed that there was a marked compression in the range of latency and absolute phase values in individual receptive fields. Second, we asked whether this timing compression reflected a reduction in the range of timings in the cortical population, perhaps with a loss of lagged-like responses. We will show that the population range was unaltered, and lagged- and nonlagged-like timings were still present. Third, we examined strobe-reared LGN and found a normal range of cell types and timings there. Fourth, we examined how lagged- and nonlagged-like timings were distributed in individual simple cells. We will show that, unlike normal cats where many simple cells show evidence of converging lagged and nonlagged inputs, such convergence is virtually absent after strobe rearing. The segregation of lagged and nonlagged timings onto different cortical cells reflected a broader action of strobe rearing, which was to reduce the timing range in virtually all simple cells.
; Humphrey and Saul 1995).
METHODS
Abstract
Introduction
Methods
Results
Discussion
References
). LGN data were obtained in four strobe-reared and five normal cats.
; Saul and Humphrey 1990, 1992a). Briefly, line-weighting functions were obtained for LGN and simple cells, respectively, by sinusoidally modulating the luminance of a stationary stimulus. For simple cells, we used an elongated, optimally oriented, narrow bar placed at 8 or 16 positions in the receptive field, and modulated the luminance at 5-7 temporal frequencies. For each bar position/temporal frequency pair, the first harmonic response amplitude and temporal phase were measured from peristimulus time histograms (PSTHs) obtained from multiple trials. For LGN cells, similar measures were obtained using a small spot always centered on, and of the same size as, the hand plotted receptive-field center. The use of spots in LGN and bars in cortex did not preclude a valid comparison of timing in the two regions, because timing in LGN cells measured with spots is very similar to that obtained with narrow bars (unpublished observations; Wolfe and Palmer 1998).
0.25 and 0 cycles or between 0.25 and 0.5 cycles. Responses with phase lags had values in the other quarter-cycles (i.e., 0.0-0.25 cycles or 0.5-0.75 cycles). For sufficiently low temporal frequencies, ON responses had phase values between 0.25 and 0.25 cycles, and OFF responses fell into the interval between 0.25 and 0.75 cycles.
0.25 and +0.25 cycles relative to the maximum (for ON responses) or minimum (for OFF responses) luminance (Saul and Humphrey 1990). Note that the absolute phase axis is circular, with 0.25 and 0.25 cycles being the same timing. For example, an ON nonlagged response of 0.25 cycles occurs at the same point in the luminance cycles as an OFF lagged response of 0.25 cycles. The second timing measure was latency; expressed in milliseconds, it is the slope of the regression line. Together, the two timing components provided signatures that allowed us to compare timings in LGN and cortex of normal and strobe-reared animals, and infer geniculocortical convergence patterns in the two rearing groups.
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FIG. 1.
Response timing measurements in 3 simple cells. A, C, and E: line-weighting functions revealing the spatiotemporal (S-T) structure of each receptive field. Each peristimulus time histogram (PSTH) was derived from responses to a stationary bar undergoing sinusoidal luminance modulation at different positions and at a fixed temporal frequency. Luminance profile is indicated beneath each set of PSTHs; 2 cycles are illustrated, for clarity. Vertical scale bar and response scaling (in impulses/s) are shown in the top right of each plot. The receptive fields had, respectively, 3, 2, and 3 ON and OFF zones. Directional (DI) and Inseparability (II) Indexes (Humphrey and Saul 1998 ) for the cells were, respectively: 0.79 and 0.89; 0.07 and 0.07; and 0.12 and 0.01. B, D, and F: mean ± SE fundamental response phase is plotted as a function of stimulus temporal frequency for each receptive-field position on the left that yielded acceptably reliable timing. Each set of points was fit by a line to estimate latency (slope, in ms) and absolute phase (intercept, in cycles), the values of which are indicated in parentheses. Values for receptive-field position reflect rounding.
). Cells in the LGN were identified as X or Y based on previously published criteria. In order of importance these were linearity of summation to counterphasing sinewave gratings (Enroth-Cugell and Robson 1966), latency to electrical stimulation of the optic chiasm, and receptive-field center size (Humphrey and Weller 1988a). Cells were also identified as lagged, nonlagged, or partially lagged by their responses to square-wave luminance-modulated spots centered in the receptive field (Humphrey and Weller 1988a; Mastronarde 1987a).
). When nonparametric statistics were required, the tests used (Siegel 1956) are indicated in the text.
RESULTS
Abstract
Introduction
Methods
Results
Discussion
References
0.25 cycles) shifts in response phase between adjacent positions (Fig. 1B). For each position, the phase versus temporal frequency plots revealed the component timings underlying the response phase values. For example, position 0.5° had a latency of 95 ms and an absolute phase lead of 0.16 cycles. Position 0.2° displayed a somewhat longer latency (127 ms) and an absolute phase lag (+0.08 cycles). These and other timings were spatially organized to produce S-T inseparability.
0.06 cycles; Fig. 1D).
View this table:
TABLE 1.
Range of response timings in individual receptive fields
; Murthy et al. 1998), and this was reflected in their narrower mean range of absolute phase and latency: 0.122 cycles and 32 ms (Table 1). Strobe rearing significantly reduced both of these ranges, to 0.068 cycles and 23 ms, respectively (P 0.035, Mann-Whitney U test). This reduction accords with the strobe-induced decrease in the Inseparability Indexes of layer 6 cells reported in the companion paper (Humphrey and Saul 1998).
0.12 ± 0.009 cycles, mean ± SE). The distribution of latencies also was quite wide, extending from about 55 to 200 ms (97 ± 1 ms). Figure 2B reveals that strobe-reared cats displayed a range of timings as wide as that in normal animals. The mean latency (96 ± 1 ms) was essentially identical to normal. However, the mean absolute phase (0.07 cycles) was shifted slightly toward zero and the distribution was narrowed (SE, 0.008 cycles). This can be appreciated in the scatter plot as a greater than normal frequency of values between 0.10 and 0.05 cycles. The change in the absolute phase distribution was statistically significant (P < 0.001) and was observed separately in layers 4 and 6. We have previously shown that absolute phase values near zero tend to reflect sustained responses, compared with values of approximately ±0.25, which reflect transient responses (Saul and Humphrey 1990). Strobe rearing thus appears to have increased the frequency of positions generating sustained visual responses. We will address the potential impact of this shift below. For now, the important point from Fig. 2 is that a full range of timing was present in the population of strobe-reared simple cells.
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FIG. 2.
Distributions of latency and absolute phase for 229 receptive-field positions in 46 cells from normal cats (A), and 303 positions in 84 cells from strobe-reared cats (B). Absolute phase values are normalized to a half cycle (see METHODS). Dashed lines are cutoff values for distinguishing lagged and nonlagged cells in the lateral geniculate nucleus (LGN). Strobe rearing did not affect the range of timings but increased the frequency of absolute phase values near 0 (see text). Note that in normal cats, the absolute phase distribution is similar to that which we reported previously for normal cats (Saul and Humphrey 1992a ), but the mean latency is ~20 ms greater than the earlier sample. The upward shift in latency may reflect the slightly lower mean luminance used in the present study (i.e., 15 vs. 25 cd/m2).
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FIG. 3.
Absolute phases observed in individual layer 4 cells. Tick marks along each bar indicate phase values measured at different receptive-field positions. As noted in METHODS, the phase axis is circular, being connected at ±0.25 cycles, but for clarity it is presented here as linear. The DI is indicated to the right of each bar. Bars are organized from bottom to top according to increasing direction selectivity. Arrows on abscissae indicate 0 absolute phase. A: in normal cats, there was a clear trend toward greater absolute phase range with increasing direction selectivity (r = 0.66, P < 0.001, Pearson correlation). Also, most direction-selective cells displayed absolute phase leads and lags. The cell labeled "DS" was highly selective during hand plotting, but its tuning was not quantified. B: in strobe-reared cats most cells were not direction selective; individual simple cells displayed much narrower absolute phase ranges that sampled phase leads or lags but rarely both. Only cells having 3 or more positions with reliable timing are included in the figure, with 2 exceptions (see Table 1 legend).
0.05 cycles. Figure 3B also reveals a tendency for absolute phase values to fall near this phase region. Might the compression in phase range among layer 4 receptive fields simply reflect a change in the underlying distribution of phase values? That is, if the range of absolute phase values in any single receptive field were to reflect mainly the frequency of timings available in the cortical population, then the greater frequency near 0.05 cycles in strobe-reared cats might account for the compressed phase range in receptive fields. We will show that a strobe-induced change in the frequency of certain timings could contribute to the compression in at most a minor way, but other factors must play a critical role.
0.05 cycles than the normal one and was somewhat narrrower. Figure 4, B and E, plots joint probability distributions, which show to what extent pairs of absolute phase values were observed in single cells. For these plots, all combinations of pairs in each receptive field were considered. The contours reflect the frequency of finding a given pair of values associated in a cell. In normal cats (B) the joint distribution was moderately wide, with a reasonable probability of finding negative and positive phase values in a cell. For strobe-reared cats (E), the joint distribution was much narrower, with phase values being similar in single receptive fields, and very few pairings of positive with negative values. This partly reflects relatively fewer absolute phases near 0.15 cycles (D). However, the distribution in D does not account for the compressive effect of strobe rearing on individual cell timing ranges, as revealed next.
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FIG. 4.
Probability distributions of absolute phase values for the layer 4 cells in Fig. 3. A and D: histograms show the probability of sampling various absolute phase values in the 2 rearing groups. Strobe rearing slightly shifted the mean value and reduced the variation in the distribution. B and E: contour lines plot the joint probability distribution: the frequency with which pairs of absolute phase values were associated in single cells. Compared with normal cats, strobe-reared animals displayed a narrow range of pairings. C and F: contour lines plot conditional probability distributions, the probability that a cell displays a particular absolute phase value (x-axis) given that it has another value (y-axis). In normal cats, associations between different values were common. After strobe rearing, only similar values tended to be associated, independent of the underlying sampling distribution. This suggests a strobe-associated process that limits inputs to a cortical cell based on their timing. Contour lines plot probabilities from 0.005 to 0.064 in B, 0.06 to 0.367 in C, 0.005 to 0.147 in E, and 0.05 to 0.888 in F, with the lowest contour in each plot identified by its value.
, what is the probability that it has another position with absolute phase value 
? Here, and are points on the vertical and horizontal axes, respectively. These probabilities were obtained by dividing the joint probabilities in B and E, respectively, by the marginal probabilities in A and D. The distribution for normal cats (C) showed strong associations between differing absolute phase values (e.g., +0.15 and 0.15 cycles). In contrast, the strobe distribution (F) was restricted to the diagonal; only similar values were associated. Another way to view these plots is to ask whether, in a cell that had one absolute phase value of, for example, 0.1 cycles, another position was likely to have a value of 0.1 or 0.1 cycles. For normal cells, either value was likely. For cells in strobe-reared cats, only the 0.1 cycles pairing was likely, despite the lower underlying probability (D) of such absolute phase values.
; Tanaka 1983) or indirectly via other cortical neurons. The present finding that a wide range of timings was present across the cortical population following strobe rearing (Fig. 2) thus led us to two hypotheses: 1) the LGN was relatively normal after strobe rearing, and 2) the rearing impacted how geniculate inputs with different timings became linked to individual cortical cells. In the following sections, we pursue these hypotheses. We first show that strobe-reared LGN was normal. We then return to cortex to show that different geniculate timing types became segregated onto different cortical cells.
); whether the suppressed cell reflects an effect of strobe rearing is unclear based on our small sample. What was clear, however, was that X and Y cells of the lagged and nonlagged types could be sampled at normal frequencies. As in normal cats (Humphrey and Saul 1992; Saul and Humphrey 1990) most (87%) of the cells recorded at these central retinal eccentricities were X type, with 31, 64, and 5% being lagged (XL), nonlagged (XN) and partially lagged (XPL), respectively. The remainder were Y cells, all but two of which were nonlagged.
; Mastronarde 1987a).
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FIG. 5.
Average responses to flashing spots of 4 ON-center LGN cells in strobe-reared cats. Spot luminance, indicated by the step profiles at bottom, was modulated over a 4-part cycle to include luminances below, equal to, above, and equal to the surrounding screen luminance. Contrast was ~0.5. Latency (in ms) of each cell to half-maximal (halfrise) and half-minimal (halffall) discharge at spot onset and offset, respectively, are indicated in parentheses. A and B: responses of an XN and YN cell. C and D: responses of 2 XL cells. Arrows and asterisks mark inhibitory dips and anomalous offset discharges, respectively. These profiles are indistinguishable from lagged and nonlagged responses in normal cats.
and Humphrey and Weller (1988a). In strobe-reared cats the latencies to flashing spots were nearly identical to those in normals (Fig. 6B). There were no differences between rearing groups in mean halfrise or halffall latency for lagged and nonlagged cells (Table 2), or in their cutoff latencies.
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FIG. 6.
Distributions of halfrise and halffall latencies for each class of LGN cells in normal (A) and strobe-reared (B) cats. Cells indicated by " 10" had halffall latencies that could not be measured due to responses having decayed to baseline before spot offset. Summary statistics for cells in the 3 major classes (XN, XL, and YN) are indicated in Table 2. Latency distributions were unaffected by strobe rearing.
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TABLE 2.
Response timing properties of LGN cells
). Strobe rearing had no obvious effect on these timing distributions (Fig. 7B). Although there were slightly fewer nonlagged cells with large phase leads, paralleling the slight reduction in these timings in cortex (Fig. 2B), there were no significant rearing-associated differences in absolute phase or latency, either across the geniculate population or within cell groups (Table 2).
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FIG. 7.
Distributions of latency and absolute phase for LGN cells in normal (A) and strobe-reared (B) cats. Summary statistics are indicated in Table 2 for the major classes. Strobe rearing had no significant effect on the timing values of any cell class.
) that strobe rearing did not alter the spatial or temporal tuning of simple cells in area 17. Likewise, within each geniculate cell class, we found no rearing effect on optimal spatial and temporal frequency or spatial and temporal resolution. There was no effect on receptive-field dimensions, and cells were normal in peak and average firing rates and in latency to optic chiasm stimulation.
,b; Mastronarde 1987a). Further, comparison of Figs. 2 and 7 indicates that the geniculate timings could account for many of the cortical timings in strobe-reared, as in normal, cats. Cortical positions with absolute phase leads and latencies <100 ms likely reflect nonlagged inputs, whereas positions with absolute phase lags and latencies >100 ms reflect lagged inputs. In both rearing groups, the slightly longer latencies observed in cortex, compared with LGN, could reflect cortical integration and the relaying of geniculate timings through other cortical neurons. Note that in both groups many cortical positions displayed timing that was neither lagged- nor nonlagged-like. Most of these "unclassifiable" positions had long latencies and absolute phase leads. They might reflect nonlagged timings whose latencies are increased intracortically via the above mechanisms. They might also reflect inputs that are subject to synaptic depression (Abbott et al. 1997; Chance et al. 1998), which, theoretically, would advance response timing in a cortical cell relative to its inputs, and increase latency.
). Predominantly lagged or nonlagged cells had 
50% of their positions identified as lagged-like or nonlagged-like, respectively, and <20% of the opposite type. Cells were deemed mixed if >20% of their positions were lagged-like and >20% nonlagged-like. Most cells also had one or more position with admissable but unclassifiable timing (e.g., Fig. 2). These positions were taken into account in calculating percentages of timing types. However, any cell with >50% of its positions deemed unclassifiable was excluded from the comparison. Using these criteria, on average 80% of the receptive-field positions in cells from both rearing groups displayed classifiable timing. Figure 8 shows the numbers of cells in the three categories for each rearing group. Although this is a rather coarse categorization, it is a convenient way of considering how the afferent timings were distributed in cortical cells. We will show that strobe rearing not only eliminated the convergence of lagged- and nonlagged-like timing, but it constricted the range of timings among cells dominated by one or the other afferent type.
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FIG. 8.
Laminar locations of cells in each of the 3 cortical cell timing categories, for each rearing group (see text for description). Error bars indicate our subjective assessment of the maximum error in assigning recording locations. On average, receptive fields in the normal (A) and strobe-reared (B) cats, respectively, had 5.4 and 4.4 positions with acceptable timing; the means were not significantly different (P > 0.05, t-test). Number of cells: normal, 69; strobe-reared, 54. The laminar distributions of response timing categories were unaffected by strobe rearing. In particular, lagged-like timing was generally restricted to lower layer 4. However, mixed cells were virtually absent after strobe rearing.
) and 38 new cells. Of these, 9 cells (13%) were predominantly lagged, 45 (65%) were predominantly nonlagged, and 15 (22%) were mixed (Fig. 8A). An example of a predominantly nonlagged cell that was not direction selective is illustrated in Fig. 1C. Six of the seven positions tested had admissable timing, and all were nonlagged-like, having latencies <100 ms and absolute phase leads. As noted above, the narrow range of timings produced an S-T separable receptive field.
0.9° and +0.2°) were lagged-like, and two were unclassifiable. As noted above, these timings produced an inseparable receptive field that was direction selective.
0.029 cycles was low. These homogeneous timings underlay the S-T separable receptive field and lack of direction selectivity.
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FIG. 9.
Example of a simple cell with predominantly lagged timing recorded in layer 4 of a strobe-reared cat. A: S-T map obtained using counterphasing bars undergoing sinusoidal luminance modulation at 1 Hz. B: response phase vs. temporal frequency data for 3 positions were fit by lines to measure latency and absolute phase, the values of which are indicated in parentheses. The cell's DI and II were 0.13 and 0.0, respectively. Conventions are as in Fig. 1.
2 test).
). Figure 8A shows the distribution for our expanded normal sample. Simple cells with predominantly nonlagged timing were concentrated in two zones: lower layer 3 through the 4/5 border zone, and layer 6. Their distribution corresponds well to the laminar terminations of nonlagged afferents (Humphrey et al. 1985). In contrast, cells with significant amounts of lagged-like timing (i.e., predominantly lagged or mixed) were largely restricted to the region extending from lower layer 4A through the 4/5 border zone, including layer 5A. We previously (Saul and Humphrey 1992a) summarized evidence that these locations correspond to the likely termination zones of lagged afferents.
DISCUSSION
Abstract
Introduction
Methods
Results
Discussion
References
) we showed that the loss of direction selectivity in simple cells resulting from strobe rearing reflects the elimination of S-T inseparable receptive-field structure. The response timings measured here provide a complementary view of these receptive fields and reveal a strobe-induced compression in the range of latency and absolute phase values in individual cells. Despite the compression, a wide range of timings was observed in the cortical population. Further, lagged and nonlagged cells appeared to be normal, and their different response timings could account for most of the cortical timings, as in normal cats (Saul and Humphrey 1992a). The strobe-induced deficit, therefore, is a failure to link inputs with different response timing onto individual cortical cells. Only inputs with similar timing become linked, and this produces S-T separable receptive fields.
; Mastronarde et al. 1991). Lagged cells also appear to receive input from intrageniculate inhibitory neurons (Humphrey and Weller 1988b), retinal activation of which appears to trigger rapid, feed-forward inhibition of the lagged cells (Mastronarde 1987b) that is mediated by GABAA receptors (Heggelund and Hartveit 1990). The inhibition accounts for the profound dip in discharge and delayed halfrise latency to flashing spots (Fig. 5C) (Heggelund and Hartveit 1990), and likely underlies the absolute phase lag measured using sinewave stimuli (Saul and Humphrey 1990). In addition, the long latencies of lagged cells and their sensitivity to inhibition may reflect a reliance on N-methyl-D-aspartate (NMDA) receptor-mediated retinal activation that is greater than among nonlagged cells (Hartveit and Heggelund 1990; Heggelund and Hartveit 1990; Kwon et al. 1991). The retinal input to nonlagged cells appears to be tied less, or not at all, to feed-forward inhibition, which results in geniculate excitation that largely mimics the temporal pattern of the retinal input (Mastronarde 1987a,b). Again, the development of these different circuits seems unaffected by the strobe paradigm. This suggests that, unlike the cortex, circuit formation in the LGN proceeds independent of the temporal properties of the afferent signal, provided that some amount of signal is present (Dubin et al. 1986). This developmental resiliency parallels the relatively limited effect of monocular lid suture on LGN development. Although that paradigm produces some reduction in Y-cell sampling (Sherman et al. 1972) and changes in some retinogeniculate arbors (Garraghty and Sur 1993), the LGN is relatively less affected than cortex (Sherman and Spear 1982).
), so both groups must have a substantial impact on cortex. 2) Lagged- and nonlagged-like timings are readily identifiable in simple-cell receptive fields (Saul and Humphrey 1992a; and present data); these timings can most simply be accounted for by inputs from the LGN. 3) Cells with the most S-T inseparable receptive fields are found in layer 4 (Humphrey and Saul 1998; Murthy et al. 1998), where the two afferent groups appear to converge. Some inseparable receptive fields there result from spatially interdigitating zones of lagged- and nonlagged-like timing. Others may achieve inseparability via a range of, for example, nonlagged-like timings. 4) Many cortical cells are direction selective at low temporal frequencies and lose their selectivity at ~4 Hz (Saul and Humphrey 1992b). This pattern is predicted by the changing temporal phase relationships between lagged and nonlagged cells with increasing temporal frequency (Saul and Humphrey 1990). 5) Cortical cooling, designed to suppress intracortical interactions, fails to reduce direction selectivity in layer 4 cells, as measured from membrane potential fluctuations (Ferster et al. 1996). This result suggests that the geniculocortical inputs convey timing information sufficient to generate directional tuning.
; Ferster and Lindstrom 1983; Martin and Whitteridge 1984). Indirect convergence via other cortical cells undoubtedly also plays a role. For example, an S-T inseparable simple cell could be created by inputs from two separable cells in approximate spatiotemporal quadrature. One input could be dominated by lagged timing and the other by nonlagged timing. Various combinations of excitatory and/or inhibitory intracortical interactions are possible. Recent work has shown that intracortical inhibition also contributes to inseparability. For some layer 4 simple cells, blocking GABAA-mediated inhibition by iontophoretic application of bicuculline concomitantly reduces S-T inseparability and direction selectivity (Murthy and Humphrey 1998). Thus a variety of geniculocortical and intracortical interactions likely play a role in producing direction selectivity. Importantly, our studies indicate that the LGN is the primary source of the response timings that underlie these interactions. We assume that the timings are distributed through, and further modified by, intracortical networks, and combined in different ways to produce S-T inseparable structure and direction selectivity.
; Suarez et al. 1995) have suggested how temporal delays may be created in cortex, with the former explicitly addressing S-T inseparability. Maex and Orban (1996) propose that inseparability arises via corticocortical feedback from simple cells with spatially offset receptive fields. The required temporal delays are produced via excitatory inputs mediated by NMDA receptors. (All LGN inputs are assumed to be nonlagged and identical in timing.) Additionally, direction selectivity is enhanced by inhibitory inputs whose preferred direction is opposite to that of the target cell.
model would not be incompatible with our suggestions on the cortical networks that relay geniculate signals. Again, the main difference between the models is the primary source of the timings: LGN versus cortex. The advantage of the geniculocortical model is that it is based on known timing differences among LGN relay cells. Its simplicity rests on the reasonable assumption that these timings are relayed through cortical networks to produce different S-T structures. Further, long timing delays (e.g., 250-1,000 ms) that are necessary to produce direction tuning at low temporal frequencies (e.g., 1-0.25 Hz) are readily accounted for in terms of known response phase differences between lagged and nonlagged cells at low temporal frequencies (Saul and Humphrey 1990, 1992b). Although, theoretically, long timing delays may be created intracortically, there is little experimental evidence that the postulated mechanisms (e.g., NMDA receptors, GABAB receptors) can produce the required delays. The synaptic depression model (Chance et al. 1998) only produces phase leads and hence cannot account for the phase lags measured in many simple cells (Humphrey and Saul 1998; Saul and Humphrey 1992a). Creating directional tuning at higher temporal frequencies (e.g., 5 Hz) requires shorter (e.g., 50 ms) delays, and intracortical mechanisms could produce them. Once again, however, the timings are already available in the nonlagged geniculate population.
) that absolute phase values near zero generally reflect sustained responses, whereas values farther from zero reflect greater response transiency. Strobe rearing thus appears to have increased the frequency of sustained responses to sinewave stimuli. At present, we cannot explain this change.
) or bars (Humphrey and Saul 1998) reveal little S-T inseparability among direction-selective layer 6 cells. Strobe rearing further reduced the weak inseparability (Humphrey and Saul 1998), which suggests that first-order structure contributes to directional tuning. However, the contribution must be small because it grossly underpredicts direction selectivity (Murthy et al. 1998). Some direction-selective simple cells with first-order separable receptive fields display second-order space-time inseparability that is revealed using two bars flashed sequentially across space. The space-time interactions can account well for cells' directional tuning (Baker and Boulton 1994; Emerson and Citron 1989). Importantly, the nature of the interactions suggests that, like layer 4 cells, inputs to the neurons arise from sources having different receptive-field locations and timing delays (Emerson 1997). The nature and source of these timings remain to be elucidated. However, a prediction from our study is that strobe rearing also produces a compression in the range of timings there. It should be possible to infer such a compression from analysis of second-order S-T maps.
, 1994; von der Malsburg 1973). We (Feidler et al. 1997) and others (Wimbauer et al. 1997a,b) recently showed that lagged and nonlagged afferents, activated by normal illumination, could be associated using Hebb-type rules to produce S-T inseparability and direction selectivity.
). Figure 10, C and D, illustrates the stimulus under continuous illumination; the luminance profile is plotted over time as the stimulus passes through the center of each receptive field in the two directions. Two cycles are shown for clarity. Figure 10, E and F, indicates the response of each unit to the stimulation. In the leftward, preferred direction, the units respond synchronously (i.e., are correlated) over approximately one-half of the stimulus cycle. The responses would sum to produce a robust discharge in the cortical cell, and their synaptic connections would strengthen. Rightward motion elicits nonoverlapping (i.e., uncorrelated) responses, which might be expected to dissociate the inputs. However, the poorer postsynaptic response in the rightward direction prevents this dissociation (Feidler et al. 1997). During continuous illumination, then, the lagged and nonlagged units should associate in cortex to generate an S-T inseparable, directionally tuned receptive field.
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FIG. 10.
Model illustrating the hypothesized effect of strobe stimulation on geniculate responses. A: receptive fields of an ON-center lagged and nonlagged unit displaced from each other by 1/4 cycle relative to a sinewave grating. Both units project to a simple cell (not shown). B: LGN unit responses to a sinusoidally modulated spot in their receptive fields; they are in temporal quadrature. C and D: luminance profiles of the grating in the center of each receptive field as a function of time, for opposite directions of motion. E and F: temporal relationships of geniculate responses evoked during continuous illumination. For leftward motion the lagged and nonlagged units respond synchronously (i.e., are well correlated) over 1/2 of the cycle, which enhances their association in cortex. For rightward motion, the responses are uncorrelated. G: during stroboscopic illumination the leftward moving grating profile is unchanged (···) but is illuminated only briefly by the strobe flash (vertical bars). H: LGN units are activated synchronously by the strobe but respond with different latencies and more transiently than normal (cf., ···). This separates the 2 responses in time, lowering their correlations and preventing them from both becoming associated with the cortical cell.
). Strobe stimulation therefore should not only prevent the association of lagged with nonlagged inputs, but reduce the probability of convergence among, for example, nonlagged inputs with different timing.
). In normally developing kittens, 8-Hz stroboscopic illumination of drifting stimuli was shown to entrain visual responses of LGN cells and to evoke short-duration discharges. Further, the latencies of lagged and nonlagged cells differed in response to the strobe stimulus, and little temporal overlap was seen in their response histograms. Latency differences were observed within each group as well. These preliminary data thus strongly support the three assumptions of the model. We are pursuing the model in additional experiments.
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ACKNOWLEDGEMENTS |
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We thank P. Baker for computer programming and M. Kieler for electronics support.
This research was supported by National Eye Institute Grants EY-06459 to A. L. Humphrey, EY-10826 to A. B. Saul, and a Core Grant for Vision Research (EY-08098) to the Eye and Ear Institute of Pittsburgh.
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FOOTNOTES |
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Address for reprint requests: A. L. Humphrey, Dept. of Neurobiology, BST E1440, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261.
Received 30 March 1998; accepted in final form 17 August 1998.
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REFERENCES |
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Abstract
Introduction
Methods
Results
Discussion
References
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