Infantile Amnesia and Generalized Fear

Infantile Amnesia

Sarah Crespi interviews Sarah Reardon about infantile amnesia, exploring why we don't remember early childhood.

The Puzzle of Infantile Amnesia

Infantile amnesia refers to the phenomenon where adults have very few, if any, memories of their infancy (the first few years of life).
Sarah Crespi's earliest memory may not be real, possibly constructed from later exposure to photos and descriptions.
Sarah Reardon remembers her family dog who died when she was three and the Gulf War when she was five.
Despite learning fundamental skills during infancy, such as eating, moving, seeing, and talking, we don't remember the process of learning them.

Theories and Explanations

Freud's Theory: Sigmund Freud coined the term infantile amnesia and attributed it to the repression of traumatic psychosexual experiences during birth.
Memory Suppression: Current evidence suggests that early memories might be suppressed rather than not formed at all.
The memories may be archived somewhere in the brain but are not easily accessible.
Immature Brain Hypothesis: Early theories dismissed infantile amnesia as a result of the immature brain's inability to form lasting memories, or the deletion of early memories to make room for new ones.

Comparative Amnesia

Many mammals, including mice and rats, also experience infantile amnesia, suggesting it is not solely tied to language development.
Precocial Mammals: Guinea pigs, which are born with their eyes open and capable of fending for themselves, do not seem to exhibit infantile amnesia.

Types of Memory

Episodic Memory: Is the memory of specific events (what, where, and when).
Contextual Memory: Is used as a proxy for episodic memory in animal studies. For example, a mouse might learn that a specific box with a patterned floor is associated with a mild shock if it steps in a certain area.

Toddler Experiments

Researchers in Berlin are conducting prospective studies on 300 toddlers to study contextual memory.
The toddlers are given experiences in specific environments (e.g., a room with spaceships), where they learn to associate certain boxes with toys.
Researchers monitor when the children start to remember these cues and information.
The same experiments are replicated in mice to correlate brain activity and understand the underlying neural mechanisms.
Around 20 months of age, toddlers start to show a shift from not remembering to remembering.
Childhood Amnesia: Memories between ages three and ten are spotty.

Optogenetics

Optogenetics helps to control specific neurons or brain regions to study memory formation.
Researchers can identify the specific neurons in the hippocampus (the brain region involved in memory processing) that encode a memory (an engram).
By labeling these neurons with a light-sensitive protein, researchers can later activate these cells by shining light on the brain.
Even if the mouse has forgotten the task, activating the engram cells can trigger the recall of the memory.

Neurogenesis

Neurogenesis, the growth of new neurons, is another hypothesis for forgetting.
As the brain grows and learns, new engrams might overwrite older ones, leading to forgetting.
In infantile amnesia, rapid neuron growth might lead to the overwriting of early memories.

Interfering with Neurogenesis

Experiments have shown that blocking neurogenesis can also block infantile amnesia.

Other Methods to Block Memory Loss

Infecting a pregnant mouse with a protein that mimics a viral infection can make the male offspring less likely to have infantile amnesia.
Separating young animals from their mothers can cause their brains to mature earlier.
Early life experiences are crucial for shaping personality and mental abilities, and interfering with brain maturation can have lasting effects.

The Importance of What the Brain Prioritizes

The brain may prioritize general learning about the world over specific memories during infancy.
For example, learning what a cat is versus remembering a specific orange cat.
The infant brain has a high capacity for learning and plasticity, which might contribute to the inaccessibility of early memories.

Critical Periods

Infant brains go through critical periods of plasticity, such as language learning.
Memory formation during these periods might be different from later in life.
Experiences during critical periods can influence brain maturation.

Implications of Understanding Infantile Amnesia

Understanding infantile amnesia could have implications for early childhood education and care (preschool, daycare).
It raises questions about the value of teaching children at very young ages.
There's a broader question of whether the forgetting in infantile amnesia is similar to forgetting in adults.
Studying infantile amnesia might provide insights into memory loss associated with Alzheimer's disease.
Optogenetic techniques and improved brain imaging are helping researchers learn more about memory formation in young children.

Naps and Brain Maturity

Research on naps suggests that children who stop napping at certain ages might have more or less mature brains.

Generalized Fear

Sarah Crespi interviews Huiquan Li about research on how the brain encodes generalized fear, a symptom of anxiety disorders.

Generalized Fear

Generalized fear is reacting fearfully to events or environments not specifically related to past stressors.
It is a symptom of anxiety disorders like panic disorder, social anxiety, and PTSD.
Generalized fear can cause stress and reduce quality of life.

Mouse Model of Generalized Fear

Researchers used a mouse model with foot shocks to trigger fear.
Conditioned fear: Mice freeze in the specific spot where they received a shock.
Generalized fear: Mice show fearful responses in novel environments where they have not experienced stress.

Neurotransmitter Changes in the Brain

Researchers observed neurotransmitter changes in the dorsal raphe, a region in the midbrain.
Serotonergic neurons in this region changed their co-transmitter from glutamate to GABA.
Normally, these neurons release serotonin as their major transmitter and co-release glutamate.
Under conditions of generalized fear, the co-transmitter switches from glutamate to GABA.
Blocking the switch from glutamate to GABA blocked generalized fear in mice.

Human Postmortem Tissue

Similar increase in serotonergic neurons co-expressing GABA synthesis was observed in postmortem brains of individuals with PTSD compared to control subjects.
The correlation and causality between the neurotransmitter switch and generalized fear production was demonstrated in the mouse model, while only a correlation was found in humans.

Effects of Prozac

Administering Prozac immediately after the foot shock prevented the development of generalized fear in mice.
However, Prozac had no effect when administered two weeks after the foot shock, once the fear response was already established.
This suggests that Prozac may prevent the switch in neurotransmitters from occurring, but it does not reverse it.

Downstream Effects of Neurotransmitter Changes

Two brain regions downstream of the dorsal raphe were identified: the central amygdala and the lateral hypothalamus.
Changes in neurotransmitter setup were observed in these regions as well.
The central amygdala and the lateral hypothalamus are known to play a role in fear regulation and anxiety-related behavior.

Causes of Neurotransmitter Switch

Stress hormones play a role in producing generalized fear.
Blocking the synthesis of corticosterone (a stress hormone) blocked both the neurotransmitter switch and generalized fear.

Therapeutic Implications

The research suggests that earlier intervention is likely to produce a better effect in treating fear-related disorders.
For chronic PTSD, new therapeutic targets are needed.

Neuronal Plasticity

The finding that neurons can switch which neurotransmitters they use challenges the classic view of neurobiology.
Traditionally, it was believed that neurons have a single, fixed neurotransmitter throughout their life.
Recent evidence shows that neurons can express multiple neurotransmitters and switch between them in response to different stimuli.
This neurotransmitter switching contributes to behavior changes.