Neonatal lead exposure impairs development of rodent barrel field cortex

Abstract

Childhood exposure to low-level lead can permanently reduce intelligence, but the neurobiologic mechanism for this effect is unknown. We examined the impact of lead exposure on the development of cortical columns, using the rodent barrel field as a model. In all areas of mammalian neocortex, cortical columns constitute a fundamental structural unit subserving information processing. Barrel field cortex contains columnar processing units with distinct clusters of layer IV neurons that receive sensory input from individual whiskers. In this study, rat pups were exposed to 0, 0.2, 1, 1.5, or 2 g/liter lead acetate in their dam's drinking water from birth through postnatal day 10. This treatment, which coincides with the development of segregated columns in the barrel field, produced blood lead concentrations from 1 to 31 microg/dl. On postnatal day 10, the area of the barrel field and of individual barrels was measured. A dose-related reduction in barrel field area was observed (Pearson correlation = -0.740; P < 0.001); mean barrel field area in the highest exposure group was decreased 12% versus controls. Individual barrels in the physiologically more active caudoventral group were affected preferentially. Total cortical area measured in the same sections was not altered significantly by lead exposure. These data support the hypothesis that lead exposure may impair the development of columnar processing units in immature neocortex. We demonstrate that low levels of blood lead, in the range seen in many impoverished inner-city children, cause structural alterations in a neocortical somatosensory map.

Figure 1

Topography of whisker pad and cortical barrel field. The individual whiskers on the rodent whisker pad are arranged in five rows [Left; postnatal day 1 (P1)]. This topographic arrangement is replicated in layer IV of somatosensory cortex, where thalamocortical afferents and their target neurons aggregate into clusters termed barrels (Right; CO histochemistry; P10).

Figure 2

Expression of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (GluR2,3) and metabotropic (mGluR2,3) glutamate receptor subunits on P10 in the barrel field of control and lead-exposed rats. Lead exposure does not alter the somatotopic pattern in the barrel field.

Figure 3

(a) Reduction in barrel field area with increasing neonatal lead exposure. (b) Reduction in barrel field area with increasing blood lead concentration. Each point represents the mean of three rats examined per litter, normalized as percentage of the control mean for that experiment. ●, experiment 1; ⧫, experiment 2.

Figure 4

(a–e) Negative correlation between lead exposure and the area of barrel field rows. The area of individual barrels in columns 1–4 of rows A–E was measured; individual barrel areas were summed within rows, and the litter mean value for each row was plotted against lead exposure level. Significant negative correlations were observed in rows B, C, and D.

Figure 5

(a–d) Negative correlation between lead exposure and the area of barrel field columns. The area of individual barrels in columns 1–4 of rows A–E was measured; individual barrel areas were summed within columns, and the litter mean value for each column was plotted against lead exposure level. A significant negative correlation was observed in column 1. (e) Summary diagram showing the spatial distribution of barrels that exhibit a significant negative correlation with lead exposure (regressions not shown). The gray line separates the barrel field into parts representing rostrodorsal and caudoventral whiskers. A significant negative correlation between barrel area and lead exposure was observed more frequently in barrels representing caudoventral whiskers.