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Comparative Study
. 2008 Jun 4;28(23):6037-45.
doi: 10.1523/JNEUROSCI.0526-08.2008.

Maternal care and hippocampal plasticity: evidence for experience-dependent structural plasticity, altered synaptic functioning, and differential responsiveness to glucocorticoids and stress

Danielle L Champagne  1 , Rosemary C Bagot, Felisa van Hasselt, Ger Ramakers, Michael J Meaney, E Ronald de Kloet, Marian Joëls, Harm Krugers
Affiliations
Comparative Study

Maternal care and hippocampal plasticity: evidence for experience-dependent structural plasticity, altered synaptic functioning, and differential responsiveness to glucocorticoids and stress

Danielle L Champagne et al. J Neurosci. .

Abstract

Maternal licking and grooming (LG) in infancy influences stress responsiveness and cognitive performance in the offspring. We examined the effects of variation in the frequency of pup LG on morphological, electrophysiological, and behavioral aspects of hippocampal synaptic plasticity under basal and stress-like conditions. We found shorter dendritic branch length and lower spine density in CA1 cells from the adult offspring of low compared with high LG offspring. We also observed dramatic effects on long-term potentiation (LTP) depending on corticosterone treatment. Low LG offspring, in contrast to those of high LG mothers, displayed significantly impaired LTP under basal conditions but surprisingly a significantly enhanced LTP in response to high corticosterone in vitro. This enhanced plasticity under conditions that mimic those of a stressful event was apparent in vivo. Adult low LG offspring displayed enhanced memory relative to high LG offspring when tested in a hippocampal-dependent, contextual fear-conditioning paradigm. Hippocampal levels of glucocorticoid and mineralocorticoid receptors were reduced in low compared with high LG offspring. Such effects, as well as the differences in dendritic morphology, likely contribute to LTP differences under resting conditions, as well as to the maternal effects on synaptic plasticity and behavior in response to elevated corticosterone levels. These results suggest that maternal effects may modulate optimal cognitive functioning in environments varying in demand in later life, with offspring of high and low LG mothers showing enhanced learning under contexts of low and high stress, respectively.

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Figures

Figure 1.
Figure 1.
Maternal behavior characterization. A, A total of five maternal observation periods per day [7:00 A.M. (07:00), 10:00 A.M. (10:00), 1:00 P.M. (13:00), 5:00 P.M. (17:00), and 8:00 P.M. (20:00)] were conducted from P1 (day of birth, P0) until P6 (D1–D6). Each observation period lasted 60 min and contained 21 observations, which were spaced by a 3 min interval. At the end of the 6 d observation period, a total of 630 observations were cumulated for each dam. B, Percentage of maternal LG across days. Low LG and high LG dams differed based on the amount of LG provided to their pups during the first week postpartum. Compared with low LG dams, the percentage of LG was consistently greater in high LG dams on each day. Note that LG scores significantly decreased over days for both high LG and low LG dams. *p < 0.05, **p < 0.01, compared with low LG dams; # p < 0.05, compared with values on day 1 within subject.
Figure 2.
Figure 2.
Quantitative morphological analysis of dendritic length. A, Representative photographs of Golgi-stained CA1 pyramidal neurons accompanied by typical drawing taken from adult rats that received low (left) versus high (right) amounts of LG in infancy. Apical dendrites on top (blue) and basal dendrites at the bottom (green) are delineated by a dotted line. Yellow marks represent typical locations where spine density was assessed. Drawings are based on three-dimensional stacks of Golgi-stained cells allowing accurate distinction between the cell of interest and neighboring cells. Note that the length of dendritic trees (both basal and apical dendrites) is significantly shorter in low LG (n = 6) compared with high LG (n = 7) offspring. Magnification, 40×. Scale bars, 200 μm. B, Representative photographs depicting spine density for low (left) and high (right) LG offspring. Basal dendrites at the top and apical dendrites at the bottom are delineated by a dotted line. Note that spine density is lower in offspring of low LG (n = 6) compared with high LG (n = 7) mothers. Magnification, 630×. Scale bars, 2.5 μm. From each cell, two 20 μm segments from the apical dendrite and one 20 μm segment from basal dendrite were analyzed (see yellow marks for typical locations in A).
Figure 3.
Figure 3.
Synaptic potentiation is impaired in low versus high licking and grooming offspring under basal conditions. Tetanic stimulation (10 Hz, 900 pulses) of Schaffer collateral afferents significantly potentiated the slope of the fEPSP in high (n = 11) but not low (n = 10) LG offspring. The bar represents the last 20 min of recording.
Figure 4.
Figure 4.
The corticosteroid receptor protein levels. A, Representative photograph of a GR Western blot normalized against α-tubulin. GR protein levels were found to be significantly reduced in low (n = 6) LG compared with high (n = 6) LG offspring. B, Representative photograph of a MR Western blot normalized against α-tubulin. MR protein levels were also found to be significantly decreased in low LG compared with high LG offspring. Note that the secondary band underneath represents nonspecific signal. L, Low LG offspring; H, high LG offspring. GR, 97 kDa; MR, 107 kDa; α-tubulin, 55 kDa.
Figure 5.
Figure 5.
Corticosteroid modulation of LTP. A, Compared with VEH conditions, a significant reduction in the percentage of fEPSPs was prominent in slices from high LG offspring pretreated with 100 nm CORT. B, In contrast, slices from low LG offspring did not display reduced but rather enhanced LTP in response to a high dose of CORT. The bar represents the last 20 min of recording.
Figure 6.
Figure 6.
Contextual fear conditioning. When contextual fear learning was assessed 24 h after conditioning, low LG animals showed significantly greater freezing in the conditioned context than high LG animals in the hippocampal-dependent version of the task (i.e., the situation where animals were allowed to form a spatial representation of the shock environment). However, maternal care did not influence the levels of freezing observed among animals conditioned in the hippocampal-independent/brief preshock interval version of the task (*p < 0.05).
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