Investigating the contribution of small conductance Ca2+ activated K+ channels to the enhancement of Pavlovian fear learning and memory through administration of apamin

Chronic activation of the amygdala through repetitive stressful events can lead to
permanent hyper-excitability of its circuitry, which is known to be the root of a number of mood
and anxiety disorders. Small conductance Ca2+-activated K+ (SK) channels expressed on lateral
amygdala (LA) pyramidal neurons shape glutamatergic postsynaptic potentials and module
NMDA receptor-dependent synaptic plasticity. When activated, SK channels reduce neuronal
excitability and LTP. Induction of synaptic plasticity in LA pyramidal neurons causes PKAmediated
internalization of SK channels from the postsynaptic density. The current study
examined whether fear conditioning would affect the subsequent sensitivity of mice to novel fear
memory encoding through SK channel blockade by the bee venom peptide, apamin. Naïve male
C57BL/6J mice received a systemic injection of apamin or saline prior to exposure to a 1 tone
(CS) - foot shock (US) conditioning protocol. Tone fear memory strength was examined 24
hours later. The next day, mice received the same or reversed treatments of saline or apamin and
were conditioned to a novel CS and context. The influence of apamin on anxiety was also
examined in the elevated plus maze to determine whether the drug was able to alter anxiety
independent of conditioning. The fear conditioning results suggest that prior fear conditioning
altered the sensitivity of mice to apamin-induced fear memory encoding during the second
conditioning session. The plus maze results indicate that solely apamin does not alter anxiety,
thus fear conditioning impairment in apamin-treated mice is not a reflection of drug effects
alone.