Intrinsic Excitability of Cocaine-Associated Memories

The neuroadaptation theory postulates that drugs of abuse harness cellular mechanisms that underlie general learning and memory processes to form addiction-related memories (Hyman et al, 2006). Recently, it has been shown that after withdrawal from repeated cocaine exposure, a small population of medium spiny neurons (MSNs) in the nucleus accumbens (NAc) are strongly activated by re-exposure to cocaine-associated stimuli, exhibiting distinct synaptic properties compared to the vast majority of NAc MSNs (Koya et al, 2012). These unique adaptations may serve to allocate specific MSNs into functional ensembles encoding cocaine-associated memories. In addition to synaptic adaptations, exposure to cocaine also alters the intrinsic membrane excitability, a parameter determining whether MSNs fire action potentials and how many to fire upon activation of excitatory synaptic inputs (Huang et al, 2011). Experience-dependent regulation of intrinsic membrane excitability is thought to be critical in allocating neurons into memory encoding ensembles (Rogerson et al, 2014)