Tell the story about the licking rat pup experiment. What did it tell us about epigenetics, and how did early life experiences affect the rat pup?
What did you personally learn about the process of gene expression? Provide an example of how a neuron’s pattern of gene expression can be influenced by something in the local cellular environment (i.e., the inside fluid constituents of the cell), and how that fluid environment of the neuron may be impacted by the broader local environment the person is actively behaving in?
After reading the Textbook and Content resources for this week, consider the phenomenological case that you also read from Oliver Sacks and reflect upon the following two points:
Conclusion on Epigenetics
The experiment provided clear evidence that:
Epigenetics is the link between environment and genome. Early life experiences (maternal care) do not change the underlying DNA sequence (genotype) but instead change the way the genes are expressed (phenotype) via epigenetic tags (like methylation).
Early life experience programs the stress response. The care received in infancy programs the brain's endocrine system for handling stress throughout life.
Personal Learning on Gene Expression
What I learned about the process of gene expression is that it is dynamic, reversible, and highly sensitive to external input. Gene expression is not a fixed blueprint dictated solely by DNA; rather, it is a real-time regulatory system that dictates which proteins are synthesized and at what level, fundamentally allowing a cell to adapt its structure and function to the immediate environment. The key takeaway is that environment and behavior are molecularly wired to the genome via epigenetic mechanisms.
Example: Neuron Gene Expression and Environment
A neuron's pattern of gene expression can be dramatically influenced by its local cellular environment:
Local Cellular Environment (Inside Fluid): The key constituent here is Calcium Ions (Ca2+). When a neuron is highly active (firing action potentials repeatedly), there is a massive influx of Ca2+ through synaptic receptors (like NMDA receptors) and voltage-gated channels into the neuron's cytoplasm.
Impact on Gene Expression: This surge in Ca2+ acts as a second messenger. It binds to various intracellular proteins, such as Calmodulin, which then activate a cascade of protein kinases (like CaMKII and MAPK). These kinases ultimately travel to the cell nucleus and phosphorylate (activate) transcription factors (e.g., CREB).
Outcome: The activated transcription factors bind to specific DNA promoters, initiating the transcription of Immediate Early Genes (IEGs)—like c-fos and BDNF (Brain-Derived Neurotrophic Factor). The protein products of these genes are critical for long-term synaptic plasticity and the formation of new memories.
Sample Answer
The Licking Rat Pup Experiment
The experiment, led by Michael Meaney and his colleagues at McGill University, focused on two groups of rat mothers:
High-Licking Mothers (HL): Mothers who naturally exhibited high levels of licking and grooming (LG) and arched-back nursing (ABN) behaviors toward their pups.
Low-Licking Mothers (LL): Mothers who naturally exhibited low levels of LG and ABN.
The Findings
The researchers found that the quality of maternal care, a purely environmental and behavioral factor, directly and permanently altered the pups' stress response systems through epigenetic modifications:
Pups of HL Mothers: These pups grew up to be less fearful, calmer, and better able to handle stress as adults. They also became high-licking mothers themselves, perpetuating the pattern.
Pups of LL Mothers: These pups grew up to be more anxious, hyper-responsive to stress, and exhibited high levels of the stress hormone corticosterone when stressed. They typically became low-licking mothers.
Epigenetic Mechanism
The study revealed the specific molecular mechanism:
Gene: The gene for the glucocorticoid receptor (GR) in the hippocampus—a brain region critical for regulating stress—was the target. The GR protein is essential for shutting down the stress response.
Modification: Licking and grooming by the mother caused a decrease in DNA methylation (the addition of a methyl group, which usually silences a gene) at the GR gene promoter region.
Outcome: Decreased methylation "opened up" the GR gene, allowing for greater transcription (gene expression). This resulted in more GR protein in the hippocampus, making the adult rat more efficient at detecting and terminating the stress response.