From precursors to myelinating oligodendrocytes: contribution of intrinsic and extrinsic factors to white matter plasticity in the adult brain.

Oligodendrocyte precursor cells (OPC) are glial cells that metamorphose into myelinating oligodendrocytes during embryogenesis and early stages of post-natal life. OPCs continue to divide throughout adulthood and some eventually differentiate into oligodendrocytes in response to demyelinating lesions. There is growing evidence that OPCs are also involved in activity-driven de novo myelination of previously unmyelinated axons and myelin remodeling in adulthood. In this review, we summarize the interwoven factors and cascades that promote the activation, recruitment and differentiation of OPCs into myelinating oligodendrocytes in the adult brain based mostly on results found in the study of demyelinating diseases. The goal of the review was to draw a complete picture of the transformation of OPCs into mature oligodendrocytes to facilitate the study of this transformation in both the normal and diseased adult brain.

Licorice and its potential beneficial effects in common oro-dental diseases.

Licorice, the name given to the roots and stolons of Glycyrrhiza species, has been used since ancient times as a traditional herbal remedy. Licorice contains several classes of secondary metabolites with which numerous human health benefits have been associated. Recent research suggests that licorice and its bioactive ingredients such as glycyrrhizin, glabridin, licochalcone A, licoricidin, and licorisoflavan A possess potential beneficial effects in oral diseases. This paper reviews the effects of licorice and licorice constituents on both the oral microbial pathogens and the host immune response involved in common ora-dental diseases (dental caries, periodontitis, candidiasis, and recurrent aphthous ulcers). It also summarizes results of clinical trials that investigated the potential beneficial effects of licorice and its constituents for preventing/treating oro-dental diseases.

A comparative study of the performance of individuals with fragile X syndrome and Fmr1 knockout mice on Hebb-Williams mazes.

Fragile X syndrome (FXS) is the most prevalent form of heritable mental retardation. It arises from a mutation in the FMR1 gene on the X chromosome that interferes with expression of fragile X mental retardation protein (FMRP) and leads to a wide range of behavioural and cognitive deficits. Previous studies have shown a deficit in basic visual perceptual processing as well as spatial abilities in FXS. How such a deficit may impact spatial navigation remains unknown. The current study extended previous research by evaluating spatial learning and memory using both virtual and physical versions of Hebb-Williams mazes, which allows for testing of humans and animals under comparable conditions. We compared the performance of individuals affected by FXS to typically developing individuals of equivalent mental age as well as the performance of Fmr1 knockout mice to wild-type control mice on the same maze problems. In human participants, performance of the comparison group improved across trials, showing expected significant decreases in both errors and latency. In contrast, the performance of the fragile X group remained at similar levels across trials. Although wild-type control mice made significantly fewer errors than the Fmr1 knockout mice, latencies were not statistically different between the groups. These findings suggest that affected humans and mice show similar spatial learning deficits attributable to the lack of FMRP. The implications of these data are discussed including the notion that Hebb-Williams mazes may represent a useful tool to examine the impact of pharmacological interventions on mitigating or reversing the symptoms associated with FXS.

Food restriction induces long-lasting recovery of spatial memory deficits following global ischemia in delayed matching and non-matching-to-sample radial arm maze tasks.

Food restriction has been shown to be beneficial for a number of brain processes. In the current study, we characterized the impact of food restriction on hippocampal damage 70 days following ischemia. We assessed memory and cognitive flexibility of ad libitum fed (AL) and food-restricted (FR) animals using complex delayed non-matching- and matching-to-sample tasks in the radial arm maze. Our findings demonstrate that food restriction led to significant improvement of ischemia-induced memory impairments. FR ischemic animals rapidly reached comparable performance as both AL and FR sham animals in delayed-non-matching (win-shift) and matching (win-stay) radial arm maze tasks. They also made considerably fewer microchoices in the retention trials than AL ischemic animals. In contrast, AL ischemic rats showed persistent spatial memory impairments in the same paradigms. Assessment of basal and stress-induced corticosterone (CORT) secretion revealed no significant differences in baseline levels in AL and FR rats prior to or following global ischemia. However, FR animals showed a more pronounced attenuation of CORT secretion 45 min following restraint. Both FR and AL ischemic rats had comparable cell loss within CA1 and CA3 subfields of Ammon's horn (CA1 and CA3) at 70 days following reperfusion, although a trend toward increased CA3 cell survival was observed in FR ischemic rats. The functional sparing in the FR ischemic animals in the face of equivalent hippocampal cell loss suggests that food restriction somehow enhanced the efficacy of remaining hippocampal or extrahippocampal neurons following ischemia. In the current study, this phenomenon was not associated with diet- and or ischemia-related alterations of vesicular glutamate transporter 1 expression in various hippocampal regions although lower vesicular GABA transporter immunostaining was present in the CA1 stratum oriens and the CA3 stratum radiatum in FR sham and ischemic rats.

Cerebral glucose transporters expression and spatial learning in the K-ATP Kir6.2(-/-) knockout mice.

K-ATP channels formed of the Sur and Kir subunits are widely distributed in the brain. Sur1-Kir6.2 is the most common combination of K-ATP channel subunits in the brain and Kir6.2 plays an important role in glucose metabolism through pancreatic insulin secretion or hypothalamic glucose sensing. K-ATP channels have also been reported to play a role in memory processing. Therefore, the aim of the present experiment is to assess the gene and protein expression of GLUT1, GLUT3 and GLUT4 in various brain regions of Kir6.2(-/-) K-ATP knockout mice and to test their working memory performance. GLUT4 was measured using two antibodies, one recognizing an intracellular epitope and the other, an extracellular epitope. Relative to their corresponding wild type, semi-quantitative immunohistochemistry showed that GLUT4 protein expression as measured by a GLUT4 antibody recognizing an extracellular epitope was increased in the Kir6.2(-/-) K-ATP mice. However, there was only a small increase in GLUT4 labeling using the GLUT4 antibody recognizing the intracellular epitope. These results suggest a compensatory higher GLUT4 inclusion at the cellular neuronal membrane in the cerebral cortex, hippocampus and cerebellum of the Kir6.2(-/-) K-ATP knockout mice. However, there was no change in GLUT4 gene expression assessed by TaqMan PCR except for a decrease in the cerebellum of these mice. Working memory performance of the Kir6.2(-/-) K-ATP mice was disrupted at age of 12 weeks but not at 5 weeks. The mild glucose intolerance that is observed in the Kir6.2 knockout mice is unlikely to have created the memory deficits observed. Rather, in light of the effects of K-ATP channel modulators on memory, the memory deficits in the Kir6.2(-/-) K-ATP mice are more likely due to the absence of the Kir6.2 and possible disruption of the GLUT4 activity in the brain.

Glucose transporter plasticity during memory processing.

Various types of learning, including operant conditioning, induce an increase in cellular activation concomitant with an increase in local cerebral glucose utilization (LCGU). This increase is mediated by increased cerebral blood flow or changes in brain capillary density and diameter. Because glucose transporters are ultimately responsible for glucose uptake, we examined their plastic expression in response to cellular activation. In vitro and in vivo studies have demonstrated that cerebral glucose transporter 1 (GLUT1) expression consistently parallels changes in LCGU. The present study is the first to investigate the effect of memory processing on glucose transporters expression. Changes in GLUT expression produced by training in an operant conditioning task were measured in the brain of CD1 mice. Using semi-quantitative immunohistochemistry, Western blot and real time RT-PCR the cerebral GLUT1 and GLUT3 expression was quantified immediately, 220 min and 24 h following training. Relative to sham-trained and naive controls, operant conditioning training induced an immediate increase in GLUT1 immunoreactivity level in the hippocampus CA1 pyramidal cells as well as in the sensorimotor cortex. At longer post-learning delays, GLUT1 immunoreactivity decreased in the sensorimotor cortex and putamen. Parallel to the changes in protein levels, hippocampus GLUT1 mRNA level also increased immediately following learning. No effect of learning was found on hippocampal GLUT3 protein or mRNA expression. Measures of changes in glucose transporters expression present a link between cellular activation and glucose metabolism. The learning-induced localized increases in GLUT1 protein as well as mRNA levels observed in the present study confirm the previous findings that GLUT1 expression is plastic and respond to changes in cellular metabolic demands.

Immunohistochemical localization and quantification of glucose transporters in the mouse brain.

A family of seven facilitative glucose transporters (Glut1-5, 7 and 8) mediates the cellular uptake of glucose. In the brain, Glut2, Glut5 and Glut8 are found at relatively low levels whereas Glut1, Glut3 and Glut4 were reported in abundance in several brain regions. Using immunofluorescence, this study investigated, compared and quantified the localization of the brain major glucose transporters, Glut1, Glut3 and Glut4, in the different cerebral areas of CD1 mice. Most of the staining of Glut1, Glut3 and Glut4 in the mouse brain coincides with observations made in rats. The results confirm the cortical neuropil distribution of Glut3, the prominence of this transporter in the mossy fiber field of the hippocampus and the Glut3 and Glut4 immunostaining of the hippocampal pyramidal cell layer. The present study also reports novel localizations of the transporters such as the presence of Glut3 in neuronal perikarya, Glut4-labeled neurons in the CA3 of the hippocampus and the subiculum. In the cerebellum, Glut3 shows subcellular localization to the base of the Purkinje cell bodies near the axon hillock. Furthermore, an important population of Golgi cells was found to be strongly immunostained for Glut4 in the granular cell layer of the cerebellum. The quantification results suggest that the relative abundance of Glut1 in the frontal and motor cortices coincides well with the high-energy demands of these brain regions. However, the Glut4-selective abundance in cerebral motor areas supports its suggested role in providing the energy needed for the control of the motor activity. The reported neuropil distribution of Glut3 seems to uphold its suggested role in synaptic energy provision and neurotransmitter synthesis. We conclude that the cellular and regional distributions of the glucose transporters in the rodent brain seem to be relevant to their corresponding functions.

The hippocampal formation--orbitomedial prefrontal cortex circuit in the attentional control of active memory.

The long held view that the hippocampal formation is not only essential, but also solely responsible for declarative memory in humans (and by analogy non-human primates) has come into question. Based on extensive reciprocal connection patterns between the hippocampal formation and the orbitoventromedial prefrontal cortex in primates and rats, a central role for the hippocampal formation in the attentional control of behavior is emerging. In this paper, evidence is reviewed showing that the hippocampal-orbitomedial prefrontal cortex circuit may be involved in attentional monitoring of the internal sensorium. This attentional monitoring system, in a sense, is the working memory of viscero-emotional processing. The hippocampal formation can thus be viewed as a discrepancy detector with respect to the relative activational status of cognitive/emotional set in the orbitomedial prefrontal cortex. Discrepancies between the current representation of the internal milieu and the "just-prior" representation held "on-line" in orbitomedial prefrontal cortex associative working memory, are signaled from the hippocampus to the prefrontal cortex prospective attentional systems to activate, process, and reconcile internal (past) with external (present) environments, and finally to effectively alter active working emotional "sets" to exert cognitive-emotional control of behavior.

Glucose and glucoregulatory modulation of memory scanning, event-related potentials and EEG in elderly subjects.

Endogenous P300b event-related potential (ERP) and behavioral performance measures, extracted during a visual memory scanning task, and spectral indices of resting electroencephalographic (EEG) activity, were assessed in 12 healthy elderly adults before and after double-blind oral administration of a placebo or glucose (50 mg) beverage. Glucoregulation was estimated by deriving a recovery index to categorize subjects as having better (BR) or poorer (PR) blood glucose recovery. Although glucoregulatory status did not impact on EEG or task performance, PR subjects exhibited reduced P300b areas relative to BR subjects prior to beverage administration. Glucose did not alter P300b or memory scanning performance but, regardless of glucoregulatory status, it increased the EEG power in the slow alpha frequency band. The study results suggest that peripheral glucoregulation can influence neuroelectric measures of cognition and that the acute ingestion of glucose can modulate central arousal processes.

Methodological and conceptual issues in the use of the elevated plus-maze as a psychological measurement instrument of animal anxiety-like behavior.

There has been some suggestion that 'risk assessment' defensive behaviors in rodents might resemble some of the behavioral/somatic symptoms of generalized anxiety in humans. Although the inclusion of some risk assessment behaviors enhanced the sensitivity of the elevated plus-maze to detect subtle changes in anxiety-like behavior, there is little evidence to support the inclusion of 15 or 20 indicator variables in an analysis. Several methodological, conceptual, complexity and interpretation problems associated with the factorial validity of recently published ethologically-derived large-scale principal components analyses of elevated plus-maze behavior are examined in this review. The utility of confirmatory factor analytic work currently being conducted in our laboratory to test structural hypotheses of anxiety-relevant elevated plus-maze behavior is then discussed with a view to address some of these issues. Finally, we propose that the growing number of measured behavioral indices in the elevated plus-maze test battery be reduced, and suggest that some of the underlying constructs thought to drive behavior in the apparatus are in need of re-evaluation.

Infralimbic muscarinic M1 receptors modulate anxiety-like behaviour and spontaneous working memory in mice.

RATIONALE: Spontaneous working memory and anxiety-like behaviour can be concurrently influenced following kappa 1 opioid agonist or antagonist infusions in the infralimbic (IL) area of the ventromedial prefrontal cortex (vmPFC) in CD-1 mice. OBJECTIVE: The present study sought to evaluate whether acetylcholine (ACh) muscarinic (M) receptor drugs can similarly influence these cognitive-behavioural processes in the IL cortex. METHOD: Anxiety was evaluated in the elevated plusmaze and spontaneous working memory was evaluated in the Y-maze following scopolamine, pirenzepine or McN-A-343 infusion in the IL cortex. RESULTS: In experiment 1, the non-specific muscarinic receptor antagonist, scopolamine, was anxiogenic in trial 1 (5, 10 and 20 nmol), but did not influence behaviour in trial 2 (no-injection) in the elevated plus-maze 24 h later. In week 2, scopolamine disrupted spontaneous working memory in the Y-maze at the highest dose (20 nmol). In experiment 2, pretreatment with the M1 antagonist, pirenzepine, was anxiolytic in trial 1 (5 and 10 nmol), as well as in trial 2 (no-injection) in the elevated plus-maze 24 h later (0.25, 1.25, 2.5, 5 and 10 nmol). In week 2, pirenzepine disrupted spontaneous working memory in the Y-maze (2.5, 5 and 10 nmol). In experiment 3, pretreatment with the M1 agonist, McN-A-343, was anxiogenic in trial 1 (2.5, 5, 10 and 20 nmol), as well as in trial 2 (no-injection) in the elevated plus-maze 24 h later (2.5, 5, 10 and 20 nmol). In week 2, McN-A-343 enhanced spontaneous working memory in the Y-maze (2.5, 5, 10 and 20 nmol). CONCLUSIONS: (1) Enhanced ACh transmission in the vmPFC induces anxiety in challenging environments and enhances spontaneous working memory performance. (2) Blocking or activating postsynaptic M1 receptors in the vmPFC may truncate or exaggerate, respectively, afferent anxiety-relevant information. (3) IL pirenzepine and McN-A-343 exert long-term opposite effects on aversive learning during trial 1 in the elevated plus-maze.

Glucose regulation and brain aging.

Blood glucose regulation is not only a complex phenomenon but glucose regulatory levels also vary significantly across individuals. Thus, whereas individuals compromised with moderately elevated blood glucose levels are diagnosed as having impaired glucose tolerance, excessive blood glucose levels render a Type II diabetes diagnosis. Type II diabetes prevalence rates in the adult population have been estimated to be between 6 and 10 percent. Although Type II diabetes has been typically associated with older people, the disease has become much more common among young adults and children. It has become increasingly evident that protracted glucose tolerance impairment usually precedes a type II diabetes diagnosis, although impaired glucose tolerance will not necessarily progress to a diabetic state. Furthermore, a number of studies have shown that impaired glucose tolerance or type II diabetes is associated with impaired cognitive function in older subjects. In addition, we recently found that cognitive deficits are also associated with moderately impaired glucose regulation in young healthy volunteers. These data, although in need of confirmation and extension, suggest that impaired glucose tolerance is associated with impaired cognition, independent of age. Moreover, since impaired glucose tolerance is more prevalent than diabetes across all ages, then our finding lead to the implication that impaired cognitive function may be more prevalent in the general population than previously estimated. Finally, the dysfunction of glucoregulatory mechanisms may be an important intervening factor when studying the evolution of cognitive function through the aging process.

Ethological confirmatory factor analysis of anxiety-like behaviour in the murine elevated plus-maze.

The elevated plus-maze has been used in animal research to measure anxiety since 1985 and is currently the most widely used animal model of anxiety. Since this paradigm has been the subject of several principal components analyses, it is well qualified for confirmatory factor analysis research. The current report builds on the substantial theoretical knowledge and empirical data obtained from these structural analyses with a view to obtain further progress in the evolution of our understanding of animal anxiety in the elevated plus-maze. The purpose of the present report was two-fold: (a) to test if the a piori imposition of a 3-factor model, or a competing 2-factor elevated plus-maze model, would fit our sample (n=200 CD-1 mice) data in each of two trials within an inferential confirmatory factor analytic framework; (b) provide a well-fitting model that confers indicator variables that can most effectively and parsimoniously measure underlying constructs of elevated plus-maze behaviour. Multiple model-fitting criteria were used, and issues related to data non-normality, outliers, replicability of the model, sampling error and error of approximation in the estimation of final model fit were addressed. The final 2-factor model, with estimated error covariance between two different pairs of indicator variables, was a good fit on the trial-1 data, although it was necessary to allow unprotected stretch attends to non-significantly cross-load on factor-2. A 2-factor model also fit the trial-2 data from the present analysis, although it was necessary to allow closed arm time ratio to negatively cross-load on factor-1. These results indicate that inferential hypothesis testing and model building procedures within a confirmatory factor analysis framework produces interpretable animal anxiety indices in the elevated plus-maze. Moreover, a 2-factor, rather than a 3-factor model, parsimoniously and unambiguously explained the underlying constructs of anxiety-like mouse behaviour in the elevated plus-maze in the present study. Taken together, a reduction in the growing number of behavioural indices reported in elevated plus-maze pharmacological studies is suggested.

Spatial and temporal distribution of chloroplast DNA polymorphism in a tropical tree species.

The level and the spatial organization of chloroplast DNA polymorphism were investigated in Dicorynia guianensis Hamshoff (Caesalpiniaceae) at different spatial and temporal scales. D. guianensis is a canopy tree of the rain forest that is distributed throughout the Guiana plateau in small aggregates. Twelve different haplotypes were identified using restriction analysis of polymerase chain reaction (PCR) amplified fragments of the chloroplast genome. When populations from different areas of French Guiana were compared, a clear geographical pattern of haplotype frequencies was identified along the Atlantic coast. This pattern is most likely the result of the restriction-expansion dynamics of the tropical forest during the Quaternary. At the local level, D. guianensis was characterized by a high level of within population diversity. Maintenance of within population diversity results from the dynamics of the aggregates; stochastic demography associated with the turnover of aggregates generates genetic differentiation among them. At the stand level, a strong spatial aggregation of haplotypes persisted from the adult to the seedling cohort indicating limited seed flow. There was also a strong difference in levels of diversity between the cohorts which suggested that recruitment over several years is needed in order to maintain genetic diversity during regeneration.

Concurrent modulation of anxiety and memory.

We have previously shown that the ventromedial prefrontal cortex (vmPFC) is involved in spontaneous working memory and anxiety-related behaviour in CD-1 mice. Specifically, pretrial microinjection of the kappa(1) agonist, U-69,593, in the infralimbic (IL) area of the vmPFC produced a robust anxiolytic behavioural profile in the elevated plus-maze and enhanced spontaneous working memory in the Y-maze. In the present study we sought to determine whether these effects were specific to IL kappa receptors. We hypothesized that microinjection of the kappa antagonist, norBNI, in the IL cortex would influence anxiety and spontaneous memory in an opposite direction to the effects produced by the kappa(1) agonist. In week 1, transfer-latency reference memory and anxiety were tested in the elevated plus-maze in two separate trials with an intertrial interval of 24 h. In week 2, spontaneous working memory was tested in the Y-maze followed immediately by defensive/withdrawal anxiety in the open field for one half of the animals in each group, and the other half was tested in reverse order. Pretreatment with one injection of vehicle, 1, 5 or 10 nmol/0.5 microl norBNI in the IL cortex dose-dependently reduced transfer-latencies and produced an anxiogenic behavioural profile in the first elevated plus-maze trial. Following a 24 h delay, transfer-latency reference memory was not influenced, but a robust anxiogenic behavioural profile was observed in the second no-injection anxiety trial in the elevated plus-maze relative to control animals. In week 2, the same groups of mice were again pretreated with one injection of the same doses of norBNI in the IL cortex and tested in the open field and Y-maze. NorBNI pretreatment was anxiogenic in the defensive/withdrawal anxiety test and disrupted spontaneous working memory regardless of testing order. The present results show the influence of kappa receptor modulation on anxiety induction and spontaneous working memory. These results also support the hypothesis that immediate memory processing may modulate the induction of anxiety-related behaviours.

U-69,593 microinjection in the infralimbic cortex reduces anxiety and enhances spontaneous alternation memory in mice.

The present report investigated the contributions of the ventromedial prefrontal cortex to the control of spontaneous alternation/working memory and anxiety-related behaviour. In Experiment 1, we examined the effects of microinjections of the selective kappa(1) receptor agonist, U-69,593, in the infralimbic cortex (IL) of CD-1 mice on several ethologically-derived anxiety indices in the elevated plus-maze (EPM) and defensive/withdrawal (D/W) anxiety in the open field, as well as on memory in the EPM transfer-latency (T-L) test and implicit spontaneous alternation memory (SAP) in the Y-maze. In week 1, pretreatment with one injection of vehicle, 1, 10 or 25 nmol/1.0 microliter U-69,593 in the IL dose-dependently prolonged T-L and produced a dose-dependent anxiolytic behavioural profile in the first EPM trial. Following a 24-h delay, the same mice were given a drug-free second trial in the EPM tests of T-L memory and anxiety. Whereas T-L memory was not disturbed, small but detectable carry-over effects were observed in trial-2 EPM behaviour relative to vehicle-treated animals. In week 2, the same groups of mice were again pretreated with one injection of the same doses of U-69,593 in the IL and given a D/W test in an open field, followed immediately by an 8-min SAP trial in the Y-maze. The smallest U-69,593 dose was anxiolytic in the D/W test, and SAP/working memory was dose-dependently enhanced in the Y-maze. In Experiment 2, we evaluated whether 0.5 microliter volume microinjections would produce comparable behavioural and carry-over effects in the IL of three new groups of CD-1 mice, in the event that the 1.0 microl volume injections used in Experiment 1 diffused beyond the IL and therefore may have confounded some effects. Experiment 2 procedures were carried out in the same manner as in Experiment 1, except the animals were tested in reverse order. Thus in week 1, SAP memory was tested in the Y-maze followed by D/W anxiety in the open field for half of the animals in each group, and the other half was tested in reverse order. In week 2, T/L memory and anxiety were tested in the EPM in 2 trials as described in Experiment 1. Pretreatment with one injection of vehicle, 10 or 25 nmol/0.5 microliter U-69,593 in the IL reduced D/W anxiety and enhanced SAP memory regardless of testing order in week 1. In week 2, the same groups of mice were again pretreated with one injection of the same doses of U-69,593 in 0.5 microliter volumes in the IL and tested in the EPM. In a similar fashion to Experiment 1, U-69,593 dose-dependently prolonged T/L and produced an anxiolytic behavioural profile in the first EPM trial. Following a 24-h delay, T/L recall memory was again not significantly influenced, but a robust anxiolytic behavioural profile was observed in the second drug-free anxiety trial in the EPM relative to vehicle-treated animals. Results are discussed relative to a) injection volumes and testing order, b) the possible influence kappa receptors may exert on neurochemical responsivity to anxiety-provoking environments in the IL area of the mPFC, c) the possibility that kappa-mediated anxiolysis from the IL in CD-1 mice results from interactions with neurochemical systems involved in the blunting of incoming anxiety-provoking information, d) evidence that SAP memory may be an implicit subtype of working memory, and e) the possibility that IL implicit working memory processes may modulate the induction and expression of anxiety-related behaviour.

Effect of glucose, glucose regulation, and word imagery value on human memory.

Changes in memory performance were examined after intake of a glucose (50 g) or saccharin (50 mg) solution in fasted men and women. Glucoregulation was estimated by using a recovery index to categorize participants within each gender as having poor or good recovery. Memory was assessed with word-learning tasks in which the imagery-evoking value of the words was systematically manipulated to yield high- and low-imagery lists. The results showed that men and women characterized as having poor glucose regulation had significantly worse memory performance under the saccharin condition. This decrement was reversed by glucose ingestion. These effects were observed for both low- and high-imagery words. This study supports the hypothesis that poor glucoregulation is associated with poor memory performance even in young healthy participants and that the ingestion of glucose can improve their memory.

New techniques in stereotaxic surgery and anesthesia in the mouse.

Mice are used in increasing numbers in neuroscience research. This increase is linked to the availability of numerous pure genetic lines and the advent of transgenic animals. Many neuroscience techniques can be used in the mouse with success, including stereotaxic placement of cannulae and electrodes. With the recent publication of a mouse brain atlas by Franklin and Paxinos and improvements in surgical procedures for the mouse, stereotaxic surgery in mice can be performed routinely and with accuracy. In the present article, we describe techniques and apparatuses for the surgical implantation of cannulae in the mouse brain. We also present new developments in anesthesia, pain management, and postoperative care that improve survival and recovery times of mice. Using these new techniques, we have gained shorter training time for students, lower mortality rates following surgery, and faster recovery.