Time setting errors in the Clock Drawing Test are associated with both semantic and executive deficits.

The common requirement to set the time to "10 past 11" on the Clock Drawing Test is intended to elicit a stimulus bound response (SBR), in which the responder is "pulled" to the salient stimulus "10," resulting in hands set at "10 before 11." SBRs are considered markers of executive dysfunction, although this assumption has not yet been validated. We compared SBR and other time-setting errors on inhibitory control tests, hypothesizing that they represent related constructs. The role of semantic dysfunction in the formation of those errors was also investigated. We examined baseline test performance of participants with Mild Cognitive Impairment or a history of depression, and control participants, enrolled in a dementia prevention study. Among 258 participants, we identified clocks with SBRs (n = 16), other time errors (n = 22), or no errors at all (n = 42). Performance between the groups with SBRs and other time-setting errors did not differ on any of the executive tests, and both error groups performed significantly worse than the No Error group on the semantic tests. Control for covariates further supported semantic and executive components in time-setting errors. Both semantic and inhibitory control deficits may underlie time representation errors in general.

Nicotinic receptor activation in perirhinal cortex and hippocampus enhances object memory in rats.

The perirhinal cortex (PRh) and its cholinergic inputs are implicated in object recognition memory. Conversely, the hippocampus (HPC) may be involved in spatial recognition processes that are not essential to the recognition of objects per se. Systemic nicotine has been shown to facilitate both object and spatial memory. The current study compared the roles of perirhinal and hippocampal nicotinic acetylcholine receptors (nAChRs) in object and spatial recognition memory using spontaneous object recognition (SOR) and object-location (OL) tasks for rats. Systemic pre-sample (acquisition) nicotine administration dose-dependently facilitated SOR and OL performance compared to vehicle conditions in which performance was at chance with a 72-h retention delay between the sample and choice phases. Subsequently, pre-sample intra-PRh infusions of nicotine significantly facilitated SOR; somewhat surprisingly, pre-sample intra-HPC nicotine also enhanced object recognition memory. Further experiments indicated facilitative effects on OL performance caused by pre-sample intra-PRh or intra-HPC nicotine administration. These results not only demonstrate that nAChR activation facilitates performance on object recognition and object-location memory tasks, but suggest that these effects can be produced by nAChR action in either PRh or HPC. Thus, although PRh and HPC are not required for OL or SOR task performance, respectively, nAChR-mediated enhancement of neural function in either of these temporal lobe regions appears capable of promoting stronger memory encoding and/or consolidation in either task. These findings further support the supposed interactive relationship between the HPC and PRh in object information processing and highlight the potential therapeutic value of nicotinic receptor activation in amnesic disorders.

Effects of an estrogen receptor alpha agonist on agonistic behaviour in intact and gonadectomized male and female mice.

Gonadal hormones mediate both affiliative and agonistic social interactions. Research in estrogen receptor alpha (ERα) or beta (ERß) knockout (KO) mice suggests that ERα increases and ERß decreases male aggression, while the opposite is found for female ERαKO and ERßKO mice. Using a detailed behavioural analysis of the resident-intruder test, we have shown that the ERß selective agonist WAY-200070 increased agonistic behaviours, such as aggressive grooming and pushing down a gonadectomized (gonadex) intruder, in gonadally intact but not gonadex male and female resident mice, while leaving attacks unaffected. The role of acute activation of ERα in agonistic behaviour in adult non-KO CD1 mice is presently unknown. The current study assesses the effects of the ERα selective agonist 1,3,5-tris(4-hydroxyphenyl)-4-propyl-1H-pyrazole (PPT) on the social and agonistic responses of gonadally intact and gonadex male and female CD1 mice to a gonadex, same-sex intruder. PPT had few effects in gonadally intact mice, but seems to increase sex-typical aggression (i.e., attacks in males, other dominance-related behaviours in females) in gonadex mice. In untreated mice, we confirmed our previous findings that gonadally intact males attacked the intruder more than females, but females spent more time engaged in agonistic behaviour than males. As in our previous results, we observed that gonadex mice generally show behaviour patterns more like those of the gonadally intact opposite sex, while leaving overall levels of agonistic behaviour unaffected. Taken together, our current and previous results show that exogenous activation of ERα had no effects in gonadally intact mice, but increased sex-typical agonistic behaviour in gonadex mice, while ERß had no effects in gonadex mice, but increased non-attack agonistic behaviour in gonadally intact animals. This suggests that, as in social recognition, ERα may be necessary for the activation of agonistic responses, while ERß may play a modulatory role.