Stephen Kelly

Asymmetric dependencies in perceiving identity and emotion: experiments with morphed faces.

We investigated whether an asymmetric relationship between the perception of identity and emo-tional expressions in faces (Schweinberger & Soukup, 1998) may be related to differences in the rela-tive processing speed of identity and expression information. Stimulus faces were morphed across identity within a given emotional expression, or were morphed across emotion within a given identity. In Experiment 1, consistent classifications of these images were demonstrated across a wide range of morphing, with only a relatively narrow category boundary. At the same time, classification reaction times (RTs) reflected the increased perceptual difficulty of the morphed images. In Experiment 2, we investigated the effects of variations in the irrelevant dimension on judgments of faces with respect to a relevant dimension, using a Garner-type speeded classification task. RTs for expression classifica-tions were strongly influenced by irrelevant identity information. In contrast, RTs for identity classifi-cations were unaffected by irrelevant expression information, and this held even for stimuli in which identity was more difficult and slower to discriminate than expression. This suggests that differences in processing speed cannot account for the asymmetric relationship between identity and emotion per-ception. Theoretical accounts proposing independence of identity and emotion perception are dis-cussed in the light of these findings.

Increased neuronal damage in apolipoprotein E-deficient mice following global ischaemia.

There is accumulating evidence that apolipoprotein E (apoE) plays a role in regulating the response to and outcome following brain injury. The present study compared the histological outcome and recovery following an episode of global ischaemia in apoE-deficient mice and wild-type littermates (12-week-old males, n = 8 per group). Transient global ischaemia was induced for a period of 17 min and the animals were allowed to recover for 72 h. Transient global ischaemia induced selective neuronal degeneration in several brain regions in wild-type mice. There was statistically significant increased ischaemic neuronal damage in apoE-deficient mice compared with wild-type mice in six of the seven regions examined (hippocampal regions CA1, CA3/CA4 and dentate gyrus; thalamus; cortex and caudate nucleus; P < 0.05). The data substantiate a role for apoE in modifying the response of the CNS to acute injury.

Targeting Expression of hsp70i to Discrete Neuronal Populations Using the Lmo-1 Promoter: Assessment of the Neuroprotective Effects of hsp70i In Vivo and In Vitro

Transgenic technology provides a powerful means of studying gene regulation and specific gene function with complex mammalian systems. In this study, the authors exploited the specific and discrete neuronal expression pattern mediated by promoter 1 of the Lmo-1 gene to study the neuroprotective effects of the inducible form of heat shock protein 70kD (hsp70i) in primary hippocampal cultures in a mouse model of global cerebral ischemia. Targeting expression of hsp70i to hippocampal neurons protected these cells significantly from toxic levels of glutamate and oxidative stress (for example, exposure to 10 μmol/L free iron produced a 26% increase in lactate dehydrogenase release from neurons cultured from wild-type mice, but a 7% increase in neurons cultured from hsp70i transgenic mice). Bilateral carotid occlusion (25 minutes) produced significantly less neuronal damage in the caudate nucleus and posterior thalamus in hsp70i transgenic mice than in wild-type littermates (for example, 21% ± 9.3% and 12.5% ± 9.0% neuronal damage in lateral caudate nucleus of wild-type and hsp70i transgenic mice, respectively, P < 0.05). The current study highlights the utility of targeted expression of transgenes of interest in cerebral ischemia and demonstrates that expression of hsp70i alone is sufficient to mediate the protection of primary neurons from denaturing stress and that expression of human hsp70i in vivo plays crucial role in determining the fate of neurons after ischemic challenge.

Cross-domain Repetition Priming in Person Recognition

Three experiments examining repetition priming of personal names are reported. In each experiment, faces are used as prime stimuli and peoples names as the test stimuli. Experiment 1 fails to demonstrate priming from faces to names when the same task—a familiar/ unfamiliar judgement—is made in prime and test phases. Experiment 2 shows that priming is observed when the same semantic judgement (British/ American) is made in prime and test phases. Experiment 3 shows that priming is observed when different semantic judgements (dead/ alive, British/ American) are made at prime and test phase. These results suggest that transfer appropriate processing cannot provide the sole account of repetition priming in person recognition. Instead, the results are interpreted in terms of a structural account of priming, embedded within an interactive activation and competition model of person recognition.

Minimal ischaemic neuronal damage and HSP70 expression in MF1 strain mice following bilateral common carotid artery occlusion

Investigation into the influence of specific genes and gene products upon the pathophysiology of cerebral ischaemia has been greatly enhanced by the use of genetically modified mice. A simple model of global cerebral ischaemia in mouse is bilateral common carotid artery occlusion (BCCAo) and the neuropathological impact of BCCAo has been investigated in several mouse strains. Bilateral carotid occlusion produces extensive neuronal damage in C57Bl/6J strain mice and this damage is linked to posterior communicating artery (PcomA) hypoplasticity in the circle of Willis. In the present study, we investigated the effect of BCCAo in MF1 strain mice and compared them with C57Bl/6J mice. The neuropathological consequences of BCCAo were assessed using standard histochemical staining and heat shock protein 70 (HSP70) immunohistochemical staining (to demarcate cells that had been ischaemically stressed). The effect of BCCAo on mean arterial blood pressure (MABP) was also measured. The plasticity of the circle of Willis was recorded using carbon black perfusion. MF1 mice displayed significantly less ischaemic neuronal damage and HSP70 immunoreactivity compared to C57Bl/6J mice following 10-20 min BCCAo. Moreover, ischaemic neuronal damage and HSP70 immunoreactivity in MF1 mice subjected to extended BCCAo (25-45 min) was never as extensive or widespread as that observed in C57Bl/6J mice after 20 min BCCAo. MABP in MF1 mice (102+/-5 mmHg) was significantly higher than in C57Bl/6J mice (87+/-5) during 20 min BCCAo. MABP in MF1 mice during 20 and 40 min (103+/-12 mmHg) BCCAo remained above pre-occlusion values for the entire occlusion period. MF1 mice had significantly greater circle of Willis plasticity (more PcomAs) than C57Bl/6J mice did. These data indicate that MF1 mice are less susceptible to BCCAo than C57Bl/6J mice and that this could be due to maintained increases in MABP during BCCAo and the lower prevalence of abnormalities of the circle of Willis in MF1 mice.

Incidental Learning of Real-World Regularities

The large literature on incidental learning relies almost exclusively on laboratory experiments. Whenever researchers have attempted to demonstrate incidental learning of real-world regularities, they have typically failed to show learning. For example, it is well established that people do not learn regularities in everyday objects, such as the left-right orientation of faces on coins, despite a very large exposure to them. In this report, we examine this apparent contradiction. We argue that most studies exploring real-life incidental learning use tests that are not as sensitive to low-confidence information as those traditionally used in laboratory tasks. Using more sensitive measures, we show that it is possible to learn regularities from British and Japanese cultural life as a direct result of exposure to these regularities. Further, confidence measures suggest that although the information may be acquired incidentally, it can be expressed with and without concomitant awareness of that knowledge.

Priming the access to names of famous faces.

There is a continuing controversy in models of face identification concerning the level of access to names relative to semantic information. In order to determine whether names are accessed sequentially after or in parallel to semantic information, we studied participants speeded decisions about famous faces that were primed by partial semantic or partial name information. Decisions that required the access to the celebritys name (one or more forename syllables, Expt 1) were significantly primed by partial name primes (initials or name fragments). However, at variance with sequential stage models, no reliable priming was observed by partial semantic primes (information about nationality, occupation, or whether a person was dead or alive). Moreover, there was a clear and consistent priming effect by partial semantic primes if the task was a nationality (British or American) decision that required the access to semantic information (Expt 2), demonstrating the effectiveness of these primes. The effects of partial name primes on nationality decisions were less consistent, with a significant effect for name fragments but not initials. However, effects of name primes were generally greater for syllable decisions than nationality decisions, and effects of semantic primes were generally greater for nationality decisions than syllable decisions. Taken together, these results favour a model of parallel rather than sequential access and suggest some degree of independence in the access to personal semantics and names.

Cerebral glucose utilization in transgenic mice overexpressing heat shock protein 70 is altered by dizocilpine

Heat shock protein (HSP70) a member of the 70u2003kDa HSP superfamily, has been widely implicated in the cellular stress response to numerous insults. HSP70 may be a significant factor in cell survival following stresses such as cerebral ischaemia. The precise mechanisms by which HSP70 facilitates cell survival remain unclear. The aim of this study was to ascertain whether any differences in local cerebral glucose utilization (LCGU) existed between transgenic mice overexpressing HSP70 (HSP70 Tg) and wild‐ type littermate (WT) mice. LCGU was assessed using 14C‐2‐deoxyglucose in HSP70 Tg and WT mice under basal conditions (intraperitoneal injection of saline) and during metabolic activation produced by NMDA receptor blockade (intraperitoneal injection of dizocilpine, 1u2003mg/kg). No significant alterations in LCGU were observed between saline injected HSP70 Tg and WT mice in any of the 35 brain regions analyzed. Dizocilpine injection produced significant heterogeneous alterations in LCGU in HSP70 Tg mice (24 of 35 brain regions) and in WT mice (22 of 35 brain regions) compared with saline injected mice. The distribution of altered LCGU produced by dizocilpine was similar in HSP70 Tg and WT mice. However in five brain regions, dizocilpine injected HSP70 Tg mice displayed significantly altered LCGU compared to dizocilpine injected WT mice (anterior thalamic nucleus +27%, dorsal CA1 stratum lacunosum molecularae+22%, dorsal CA1 stratum oriens+u200a14%, superior olivary body −26%, and the nucleus of the lateral lemniscus −16%). These data highlight that while overexpression of HSP70 transgene does not significantly alter LCGU in the basal state, mice overexpressing the HSP70 transgene respond differently to metabolic stress produced by NMDA receptor blockade in some important brain regions.

MiR-132 Is Upregulated by Ischemic Preconditioning of Cultured Hippocampal Neurons and Protects them from Subsequent OGD Toxicity

We explored the response of a panel of selected microRNAs (miRNAs) in neuroprotection produced by ischemic preconditioning. Hippocampal neuronal cultures were exposed to a 30-min oxygen–glucose deprivation (OGD). In our hands, this duration of OGD does not result in neuronal loss in vitro but significantly reduces neuronal death from a subsequent ‘lethal’ OGD insult. RT-qPCR was used to determine the expression of 16 miRNAs of interest at 1 and 24-h post-OGD. One miRNA (miR-98) was significantly decreased at 1-h post-OGD. Ten miRNAs (miR-9, miR-21, miR-29b, miR-30e, miR-101a, miR-101b, miR-124a, miR-132, miR-153, miR-204) were increased significantly at 24-h post-OGD. No miRNAs were decreased at 24-h. The increases observed in the 24-h group suggested that these miRNAs might play a role in preconditioning-induced neuroprotection. We selected the widely studied miR-132, a brain enriched, CREB regulated miRNA, to explore its role in simulated ischemic insults. We found that hippocampal neurons transduced with lentiviral vectors expressing miR-132 were protected from OGD and NMDA treatment, but not hydrogen peroxide. These findings add to the growing literature that targeting neuroprotective pathways controlled by miRNAs may represent a therapeutic strategy for the treatment of ischemic brain injury.