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Maternal Programming of Defensive Responses 155the tactile stimulation derived from maternal licking/grooming. Maternal deprivationalso decreases the expression of brain-derived neurotrophic factor (BDNF)expression in neonates (Roceri et al., 2002; Zhang et al., 1997). The results ofthese studies suggest that tactile stimulation derived from maternal licking/groomingcan serve to promote an endocrine or paracrine state that fosters growth anddevelopment. cDNA array analyses (Diorio et al., 2000) reveal major classes ofmaternal effects on hippocampal gene expression in postnatal Day 6 offspring,including (1) genes related to cellular metabolic activity (e.g., glucose transporter,cFOS, cytochrome oxydase, LDL receptor), (2) genes related to glutamate receptorfunction, including effects on the glycine receptor, as well as those mentionedfor the NMDA receptor subunits, and (3) genes encoding for growth factors, includingBDNF, bFGF, and ß-NGF. In each case, expression was greater than3-fold higher in hippocampal samples from offspring of High compared to LowLG-ABN mothers.Variations in maternal care are also associated with individual differences inthe synaptic development of selected neural systems that mediate cognitive development.As adults, the offspring of High LG-ABN mothers show enhancedspatial learning/memory in the Morris water maze (Liu et al., 2000), as well as inobject recognition (Bredy et al., 2003a,b). The performance in both tasks is dependenton hippocampal function (e.g., Morris et al., 1986; Whishaw, 1998), andmaternal care alters hippocampal synaptogenesis. At either Day 18 or Day 90,there was evidence of increased synapse formation/survival in hippocampalsamples from the High LG-ABN offspring. More recent studies reveal significanteffects of maternal care on neuron survival in the hippocampus (Bredy et al., 2004),as well as on hippocampal LTP (Bredy et al., 2003a,b). There was increased evidencefor long-term neuron survival of cells generated during the first week ofpostnatal life in the offspring of High compared with Low LG-ABN mothers.Naturally occurring variations in maternal licking/grooming and arched-backnursing are associated with the development of cholinergic innervation to the hippocampus,as well as differences in the expression of NMDA receptor subunitmRNAs. These findings provide a mechanism for the differences observed inspatial learning and memory in adult animals. In the adult rat, spatial learning andmemory is dependent on hippocampal integrity; lesions of the hippocampus resultin profound spatial learning impairments. These results are also consistentwith the idea that maternal behavior actively stimulates hippocampal synaptogenesisin offspring through systems known to mediate experience-dependentneural development (e.g., Kirkwood et al., 1993; Schatz, 1990).These findings suggest that maternal care in the rat directly influences hippocampaldevelopment through effect on the expression of genes involved in bothneuron survival and synaptic development. The group differences in performancein the Morris water maze are consistent with a maternal effect on cognitive