The original work on sensitive periods in dogs, done largely in the 1950s and 1960s assumed that adequate exposure to appropriate physical and social environments was a main issue affecting early behaviors of dogs. The classic work of Scott and Fuller and those encouraged by them also focused on comparisons between breeds, and later on selecting for genetic lines of extreme behavior. The focus on genetics was on behaviors that followed classic rules of inheritance. No one was thinking about pre-, peri- and post-natal epigenetic effects (changes in the ways genes are expressed) on neurodevelopment. And certainly no one was considering a dog like the lovely Missy Rose whose brain had been deprived of protein for most of her life.
There are few data on effects of anxiety on learning in dogs, but we know from studies on rodents and human children that chronic glucocorticoid (steroid) excess – at any time, including pre- and peri-natally - interferes with learning at the cellular/molecular levels. Chronic glucocorticoid exposure at these periods also appears to affect the structural development of the hippocampus – the brain region responsible for associational learning and its further integration into cortical function - and the amygdala – the brain region responsible for developing and modulating fear. Chronic cortisol (a hormone produced by the body in response to stress) elevation appears to act as a translational gene regulator— a hormonal response element— that interferes with acquisition and consolidation of task learning in regions of the hippocampus. Pre-natal stress and chronic ongoing stress in rats leads to lower levels of extinction of cue-conditioned fear, causes shrinkage of the hippocampus, which, in turn, leads to memory impairment, and facilitates fear conditioning in the amygdala, especially for consolidation of auditory fear conditioning. These effects are now known to be more pronounced in some genetic backgrounds, mean that the role for traditional inheritance just became more complex.
These studies suggest potential mechanisms for the finding that puppies separated early experienced more fearfulness on walks, reactivity to noises and overall enhanced reactivity as adults than did those allowed to stay with their dams and littermates. One has to wonder whether those humans willing to rush pups out the door would do so if they knew about the potential for epigenetic effects. We should encourage everyone to focus on providing the best environment for the bitch, and hence the pups, during pregnancy. If early adoption co-occurs with less-than-optimal breeding and pregnancy practices, pups can have real problems.
Prenatal exposure to maternal stress causes epigenetic methylation – addition of a CH3 complex - of glucocorticoid receptor genomic promoter regions, which causes hyper-reactivity in rodents and humans. In rodents, hippocampal expression of the glucocorticoid receptor gene and behavioral responses to stress are affected by the amount of care mothers give young in the first few days of life, a process that I would postulate likely also occurs in dogs.
These studies show that task learning can be enhanced when stress and distress are mitigated. Raising puppies with their siblings and dam through 70 days, a time when most brain myelination is complete, but when neuronal remodeling should be rapidly ongoing, provides such mitigation.
These emergent, complex neurobiological findings can be distilled to a few simple guidelines for breeding and raising pups. Considering the enhanced risk of relinquishment, abandonment and euthanasia for dogs with any behavioral concerns, welfare and behavioral standards should mandate that puppies remain with their litters in the home of, and with access to the dam and sibling through 8 weeks of age, and that puppies, bitches and dams be exposed to humane conditions that minimize the risks of excess stress and fear.
What does all of this mean for the lovely Missy Rose? In addition to simply being adopted to young, it’s like that a dog like the lovely Missy Rose was exposed to a series of damaging epigenetic effects. Given her source, it is also possible that fast reacting dogs were preferred and she may have a set of genes that might make some aspect of her reactivity more appealing in another environment (eg, moving livestock). Her gastrointestinal illness not only deprived her of the nutrition needed for normal body and brain growth and development, but may also have acted as an ongoing stressor that could further damage her neurons.
Yet, with dietary treatment, an enhanced diet, behavior modification to help calm her, and behavioral medication to help her to learn more and react less…..the lovely Missy Rose is slowly improving. This is the best she has ever been, and I know I will say the same thing tomorrow, next month and next year. She is the poster child for ensuring that everyone knows that simply by caring for their developing brains, we spare pups the risk of debilitating, tragic and often lethal behavioral problems and avoid lives marked by profound fear and reactivity.
©Karen L. Overall, MA, VMD, PhD, DACVB, CAAB
 Scott JP, Fuller JL: Genetics and the Social Behavior of the Dog. University of Chicago Press, Chicago, 1965.