The amygdala is a key structure of the limbic system with a role in the perception of fear, the fear response

and learned fear memory and reduced activity of this region appears to contribute to panic disorder.
Research finds individuals who report reduced panic attacks and symptoms following therapeutic
intervention still demonstrate avoidant behaviour indicating that there is some artifact that remains as a
learned fear memory which may provide an explanation for the effects of CBT [13]. Furthermore,
volumetric MRI studies on individuals with panic disorder were found to have amygdalar atrophy [14]. It is
hypothesized that the amygdala mediates the panic response through its output to the thalami, brainstem
regions and activates the HPA axis , with observed changes in pituitary volume and levels of stress
hormones following a panic attack[15] [16]. However, there is conflicting evidence regarding the involvement of
the HPA axis and other regulatory pathways have been suggested, particularly through the PAG [17]. The
amygdala may be activating panic circuits in response to rising levels in CO2 and changes in brain pH
through pH sensitive ASIC1a ion channels that are required for contextual fear [18]. ASIC1a channels are
numerous in the amygdala and knockout experiments demonstrated a resulting deficit in conditioned and
unconditioned fear in mice, so the ability of this channel to detect local changes in pH and cause a
response in the amygdala may be the basis for the fear conditioning of internal sensation that is believed to
underlie the onset of panic attacks[19].This may be the basis for the fear conditioning of internal sensation
that underlies the onset of panic attacks.