These molecular consequences are consistent with the alterations in plasticity and memory caused by sNS at the synaptic level. Our data demonstrate the cognitive impact of sNS and associate memory deficits with specific alterations in glutamatergic synaptic function.

The impact of a single seizure on cognition remains controversial. We hypothesized that a single early life seizure (sELS) on rat post-natal day (P) 7 would alter only hippocampal-dependent learning and memory in mature (P60) rats. The Morris Water Maze (MWM), Novel Object and Novel Place Recognition (NOR/NPR) tasks, and Contextual Fear Conditioning (CFC) were used to assess learning and memory associated with hippocampal/prefrontal cortex, perirhinal/hippocampal cortex, and amygdala function, respectively. The Elevated Plus Maze (EPM) and Open Field Test (OFT) were used to assess anxiety associated with the septum. We report that sELS impaired hippocampaldependent short-term memory but not spatial learning or recall. sELS did not disrupt performance in the NOR/NPR. CFC performance suggested intact amydgala function. sELS did not change anxiety levels as measured by the EPM or OFT. Our data suggests that the long-term cognitive impacts of sELS are largely limited to the hippocampus/prefrontal cortex.

No abstract

Stimulation of nicotinic receptors, specifically the α7 subtype, improves sensory inhibition and cognitive function in receptor deficient humans and rodents. However, stimulation with a full agonist, such as nicotine, produces rapid tachyphylaxis of the P20N40-measured sensory inhibition process. 3-(2,4-dimethoxybenzylidine) anabaseine (DMXBA, also GTS-21) selectively activates the α7 nicotinic receptor, and in acute administration studies, has been shown to improve deficient sensory inhibition in both humans and rodents with repeated dosing. Unlike nicotine, this partial agonist acted without inducing tachyphylaxis. Here, we assessed the ability of DMXBA to improve sensory inhibition in DBA/2 mice after 7 days continuous administration via a subcutaneously implanted osmotic minipump. When assessed on day 8, mice receiving saline showed the characteristic deficient sensory inhibition seen with untreated DBA/2 mice. The 25 and 50 mg/ml infusion concentrations of DMXBA, but not the 100 mg/ml, produced significantly improved sensory inhibition in the mice, exclusively through a decrease in test amplitude. No concentration significantly upregulated hippocampal α7 receptor levels. DMXBA levels in the brain were higher than plasma at 2 of the 3 concentrations infused. These data suggest that continuous exposure to DMXBA does not significantly affect the underlying responsiveness of the sensory inhibition pathway to this partial agonist, nor cause receptor upregulation, at these relatively low brain concentrations. The ability of DMXBA to maintain its effectiveness during constant administration conditions may be due to an ability to activate α7 receptors at low concentrations, and consequently low fractional occupancy of the five possible binding sites on this homomeric receptor.

No abstract