Sanguinetti, Shannon

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.

Small conductance Ca2+-activated K+ (SK) channels have been shown to alter the encoding of spatial and non-spatial memory in the hippocampus by shaping glutamatergic postsynaptic potentials and modulating NMDA receptor-dependent synaptic plasticity. When activated, dendritic SK channels reduce hippocampal neuronal excitability and LTP. Similar SK channel properties have been demonstrated in lateral amygdala (LA) pyramidal neurons. Additionally, induction of synaptic plasticity and beta-adrenoreceptor activation in LA pyramidal neurons causes PKA-mediated internalization of SK channels from the postsynaptic density. Chronic activation of the amygdala through repetitive stressful stimuli can lead to excitatory synaptic strengthening that may create permanent hyper-excitability in its circuitry. This mechanism may contribute to a number of mood and anxiety disorders. The selective influence of SK channels in the LA on anxiety and fear conditioning are not known. The thesis project outlined herein examined whether SK channel blockade by bee venom peptide, apamin, during a repetitive acute fear conditioning paradigm was sufficient to alter fear memory encoding and the resulting behavioral outcome. Following the final fear memory test session, mice were tested in the open field immediately after the second fear conditioning test session. The findings indicate that intracranial LA microinfusions of apamin did not affect memory encoding or subsequent anxiety.