Lactate transporters in the rat barrel cortex sustain whisker-dependent BOLD fMRI signal and behavioral performance

Lactate is an efficient neuronal energy source, even in presence of glucose. However, the importance of lactate shuttling between astrocytes and neurons for brain activation and function remains to be established. For this purpose, metabolic and hemodynamic responses to sensory stimulation have been measured by functional magnetic resonance spectroscopy and blood oxygen level-dependent (BOLD) fMRI after down-regulation of either neuronal MCT2 or astroglial MCT4 in the rat barrel cortex. Results show that the lactate rise in the barrel cortex upon whisker stimulation is abolished when either transporter is down-regulated. Under the same paradigm, the BOLD response is prevented in all MCT2 down-regulated rats, while about half of the MCT4 down-regulated rats exhibited a loss of the BOLD response. Interestingly, MCT4 down-regulated animals showing no BOLD response were rescued by peripheral lactate infusion, while this treatment had no effect on MCT2 down-regulated rats. When animals were tested in a novel object recognition task, MCT2 down-regulated animals were impaired in the textured but not in the visual version of the task. For MCT4 down-regulated animals, while all animal succeeded in the visual task, half of them exhibited a deficit in the textured task, a similar segregation into two groups as observed for BOLD experiments. Our data demonstrate that lactate shuttling between astrocytes and neurons is essential to give rise to both neurometabolic and neurovascular couplings, which form the basis for the detection of brain activation by functional brain imaging techniques. Moreover, our results establish that this metabolic cooperation is required to sustain behavioral performance based on cortical activation.

In the past 25 y, a major revolution in the field of brain energy metabolism has occurred. While it was believed classically that glucose is the sole valuable energy substrate for neurons, it is now admitted that under certain circumstances, alternative substrates can serve as fuels and replace glucose, at least partially, even in the adult brain. This is the case for lactate. Indeed, it was shown that lactate provided from the periphery through the blood circulation is efficiently used by the brain in animals (1) and humans (2–4). In addition to peripheral supply, the brain itself has the capacity to internally produce lactate from blood-borne glucose. This process of activity-dependent lactate transfer is named the astrocyte–neuron lactate shuttle (ANLS) (5) and has received a large support in the literature based on in vitro (6, 7), ex vivo (1), and in vivo experiments (8–11). It was also shown that lactate supply by glial cells to neurons is a fundamental process that has been conserved during evolution, as it was found to be present in invertebrates as well (e.g., flies) (12, 13). Nevertheless, some recent studies have provided evidence that direct glucose utilization by neurons also takes place during activation (14, 15). It might be essential for some aspects of neurotransmission (16) or when metabolized via the pentose phosphate pathway to regenerate glutathione and ensure antioxidant protection (17). These observations call for further in vivo investigations to assess the contribution of these energy-supply modes to sustain brain activities, ranging from metabolic and hemodynamic responses associated with brain activation to behavioral performances.It has been well documented that activation of a brain region (e.g., hippocampus or cortex) leads to a transient increase in lactate concentration within the activated area in rodents (18–20) and in humans (21, 22). Such an observation might reflect a transient mismatch between lactate production attributed to astrocytes and utilization/disposal by other brain cells, although the importance of each remains to be confirmed in vivo. The capacity to release or utilize lactate is determined by the expression of specific transporters, named monocarboxylate transporters (MCTs). Three members of this family have been identified in the central nervous system (23): MCT2 is the predominant neuronal lactate transporter (24); MCT4 expression is prominent on astrocytes (25); while MCT1 expression is more ubiquitous with strong expression on endothelial cells of blood vessels as well as on glial cells (26). Previously, it was shown that reducing MCT2 expression (which allows neuronal lactate uptake) interfered with blood oxygen level-dependent (BOLD) fMRI signal, which depends on local, activity-dependent change in blood flow and is used as a surrogate marker for neuronal activity to perform functional brain imaging (20). Recently, new viral vector tools have been developed that allow the down-regulation of either MCT2 or MCT4 expression in a cell-specific manner in vivo (27). In the present study, we took advantage of this approach to determine the importance of both transporters—and by extension, of lactate shuttling between astrocytes and neurons—in both metabolic and hemodynamic responses, as well as in behavioral performances associated with activation of the whisker-to-barrel system in rats.     

When and why parents involve young children in video communication*

Recent media reports have suggested video communication use by young children. However, the popularity of video communication by young children has yet been determined. Although some research has shown similarities between young children’s experience of a parent’s physical and virtual presence, little is known about the ecological applications of video communication and its benefits to young children. Using a brief quantitative questionnaire, this study shows that younger children started video communication at significantly earlier ages than the older children in the sample (n = 308). Qualitative responses from parents of 17 children suggested different perceptions of their children's video communication experience. These preliminary findings are considered in the context of the value of video communication in different situations, the developmental factors associated with screen media including memory transfer across modalities, and the development of skills that facilitate effective communication.     

Differential lateralization for words and faces: category or psychophysics?

This set of three experiments assessed the influence of different psychophysical factors on the lateralization of the N170 event-related potential (ERP) component to words and faces. In all experiments, words elicited a left-lateralized N170, whereas faces elicited a right-lateralized or nonlateralized N170 depending on presentation conditions. Experiment 1 showed that lateralization for words (but not for faces) was influenced by spatial frequency. Experiment 2 showed that stimulus presentation time influenced N170 lateralization independently of spatial frequency composition. Finally, Experiment 3 showed that stimulus size and resolution did not influence N170 lateralization, but did influence N170 amplitude, albeit differentially for words and faces. These findings suggest that differential lateralization for words and faces, at least as measured by the N170, is influenced by spatial frequency (words), stimulus presentation time, and category.     

The utility of diagnostic laparoscopy in the evaluation of anterior abdominal stab wounds

Background

To assess if diagnostic laparoscopy (DL) is superior to nonoperative modes (serial abdominal examination with/without computed axial tomography [CAT] and diagnostic peritoneal lavage) in determining the need for therapeutic laparotomy (TL) after anterior abdominal stab wound (ASW).

Methods

Retrospective review of ASW patients. Patients were divided into group A (DL/exploratory laparotomy) to identify peritoneal violation (PV) and group B (initial nonoperative modes).

Results

Seventy-three patients met inclusion criteria. In group A (n = 38), 29 patients (76%) had PV by DL and underwent exploratory laparotomy. Only 10 (35%) underwent TL (sensitivity for PV = 100%; specificity and positive predictive value of PV in determining need for TL = 29% and 33%, respectively). In group B (n = 35), 7 patients (20%) underwent TL, yielding an improved specificity (96%) and positive predictive value (88%).

Conclusions

We find no role for DL in the evaluation of ASW patients solely to determine PV.     

There's alcohol in my soap: portrayal and effects of alcohol use in a popular television series

Two studies are reported addressing the media influences on adolescents' alcohol-related attitudes and behaviours. A content analysis was conducted to investigate the prevalence of alcohol portrayal in a Dutch soap series. The coding scheme covered the alcohol consumption per soap character, drinking situations and drinking times. Inter-coder reliability was satisfactory. The results showed that alcohol portrayal was prominent and that many instances of alcohol use reflected undesirable behaviours. To assess the influence of such alcohol cues on adolescents, a 2x2 experiment was conducted focusing on the separate and combined effects of alcohol portrayal in the soap series and surrounding alcohol commercials. Whereas the alcohol commercials had the expected effects on adolescents' attitudes, the alcohol-related soap content only appeared to have unexpected effects. Adolescents who were exposed to the alcohol portrayal in the soap series had a less positive attitude towards alcohol and lower drinking intentions. Implications of these findings for health policy and future research are discussed.