Fear conditioning
A number of theorists have argued that conditioned fear coincides substantially with the mechanisms, both functional and neural, of clinical anxiety disorders.
While studying rats' ability to recall fear memories, researchers found a newly identified brain circuit is involved.
Initially, the pre-limbic prefrontal cortex (PL) and the basolateral amygdala (BLA) were identified in memory recall.
In particular, the expressions of immediate early genes (IEGs) such as Egr1, c-Fos, and Arc are rapidly and selectively up-regulated in subsets of neurons in specific brain regions associated with learning and memory formation.
Expression of DNMT3A2 proteins in hippocampus neurons in culture preferentially targeted the addition of new methylation to more than 200 genes involved in synaptic plasticity.
[20] Electrophysiological recordings from the amygdala have demonstrated that cells in that region undergo long-term potentiation (LTP), a form of synaptic plasticity believed to underlie learning.
Therefore, even in situations of uncertainty and not necessarily fear, the amygdala plays a role in alerting other brain regions that encourage safety and survival responses.
Some theoretical accounts of traumatic experiences suggest that amygdala-based fear bypasses the hippocampus during intense stress and can be stored somatically or as images that can return as physical symptoms or flashbacks without cognitive meaning.
[27] The hippocampus is one of the brain regions that undergoes major alterations in gene expression after contextual fear conditioning.
Contextual fear conditioning applied to a rat causes about 500 genes to be up-regulated (possibly due to DNA demethylation of CpG sites) and about 1,000 genes to be down-regulated (observed to be correlated with DNA methylation at CpG sites in promoter regions) (see Regulation of transcription in learning and memory).
The pattern of induced and repressed genes within hippocampal neurons appears to provide a molecular basis for forming the early transient memory of contextual fear conditioning in the hippocampus.
Dopamine neurons in the ventral tegmental area, substantia nigra pars compacta, and dorsal raphe nucleus play a critical role in forming, consolidating, and retrieving fear-related memories.
Those subsequent generations of mice also showed a behavioral sensitivity to acetophenone, which was accompanied by neuroanatomical and epigenetic changes that are believed to have been inherited from the parents' gametes.
[36] The learning involved in conditioned fear, as well as the underlying neurobiology, changes dramatically from infancy, across childhood and adolescence, into adulthood and aging.
[37] Previous research has indicated that adolescents show hampered fear extinction learning compared to children and adults.
[38] This finding may have clinical implications, as one of the most widely used treatments for anxiety disorders is exposure based therapy, which builds on the principles of fear extinction.
The exact mechanisms underlying the developmental differences in fear extinction learning have not yet been discovered, although it has been suggested that age related differences in connectivity between the amygdala and medial prefrontal cortex can be one of the biological mechanisms underpinning the developmental change in fear extinction learning.
Biological mechanisms underpinning SEFL have not yet been made clear, though it has been associated with a rise in corticosterone, the stress hormone, following the initial stressor.
