Infusing zeta inhibitory peptide into the perirhinal cortex of rats abolishes long-term object recognition memory without affecting novel object location recognition.

Infusing the amnesic agent zeta inhibitory peptide (ZIP) into the dorsal hippocampus disrupts established long-term object location recognition memory without affecting object identity recognition, which likely depends on the perirhinal cortex. Here, we tested whether infusing ZIP into the perirhinal cortex can abolish long-term memory supporting object identity recognition, leaving long-term object location recognition memory intact. We infused ZIP into the perirhinal cortex of rats either 1 day or 6 days after exposing them to two identical objects in an open field arena. One day after ZIP infusion, that is, 2 or 7 days after object exposure, we either assessed whether the animals recognized that now one of the two objects was novel or whether they recognized that one of the two familiar objects was at a new location. Our results show for both retention intervals, infusions of ZIP into the perirhinal cortex impaired novel object recognition but spared novel object location recognition. Rats that received a scrambled version of ZIP had no deficit in either test at both retention intervals and expressed stronger novel object recognition compared to rats infused with ZIP. These findings support the view that object recognition depends on dissociable memory representations distributed across different brain areas, with perirhinal cortex maintaining long-term memory for what objects had been encountered, and hippocampus supporting memory for where these objects had been placed.

Microglial TNF-α Suppresses Cocaine-Induced Plasticity and Behavioral Sensitization.

Repeated administration of cocaine results in the development of behavioral sensitization, accompanied by a decrease in excitatory synaptic strength in the nucleus accumbens (NAc) through an unknown mechanism. Furthermore, glial cells in the NAc are activated by drugs of abuse, but the contribution of glia to the development of addictive behaviors is unknown. Tumor necrosis factor alpha (TNF-α), an inflammatory cytokine released by activated glia, can drive the internalization of synaptic AMPA receptors on striatal medium spiny neurons. Here we show that repeated administration of cocaine activates striatal microglia and induces TNF-α production, which in turn depresses glutamatergic synaptic strength in the NAc core and limits the development of behavioral sensitization. Critically, following a period of abstinence, a weak TLR4 agonist can reactivate microglia, increase TNF-α production, depress striatal synaptic strength, and suppress cocaine-induced sensitization. Thus, cytokine signaling from microglia can regulate both the induction and expression of drug-induced behaviors.