Beyond the Stress Concept: Allostatic Load-A Developmental Biological and Cognitive Perspective

Here we report that increased pup licking and grooming (LG) and arched-back nursing (ABN) by rat mothers altered the offspring epigenome at a glucocorticoid receptor (GR) gene promoter in the hippocampus. Offspring of mothers that showed high levels of LG and ABN were found to have differences in DNA methylation, as compared to offspring of 'low-LG-ABN' mothers. These differences emerged over the first week of life, were reversed with cross-fostering, persisted into adulthood and were associated with altered histone acetylation and transcription factor (NGFI-A) binding to the GR promoter. Central infusion of a histone deacetylase inhibitor removed the group differences in histone acetylation, DNA methylation, NGFI-A binding, GR expression and hypothalamic-pituitary-adrenal (HPA) responses to stress, suggesting a causal relation among epigenomic state, GR expression and the maternal effect on stress responses in the offspring. Thus we show that an epigenomic state of a gene can be established through behavioral programming, and it is potentially reversible.

Episodic memory is a neurocognitive (brain/mind) system, uniquely different from other memory systems, that enables human beings to remember past experiences. The notion of episodic memory was first proposed some 30 years ago. At that time it was defined in terms of materials and tasks. It was subsequently refined and elaborated in terms of ideas such as self, subjective time, and autonoetic consciousness. This chapter provides a brief history of the concept of episodic memory, describes how it has changed (indeed greatly changed) since its inception, considers criticisms of it, and then discusses supporting evidence provided by (a) neuropsychological studies of patterns of memory impairment caused by brain damage, and (b) functional neuroimaging studies of patterns of brain activity of normal subjects engaged in various memory tasks. I also suggest that episodic memory is a true, even if as yet generally unappreciated, marvel of nature.