Nevertheless, these findings provide evidence showing that Acb NM

Nevertheless, these findings provide evidence showing that Acb NMDA receptors play an important role in the expression of ethanol-conditioned behavior. “
“Neurons and glia in the central nervous system originate from neural stem and progenitor cells that reside in the ventricular zones. Here we examine the role of β-catenin in neural stem cell (NSC) regulation in mouse embryos lacking β-catenin specifically in the brain germinal zone. PD0332991 An in vitro clonal neurosphere assay was performed in order to ascertain the status of the NSC population. Intact

neurospheres did not form from β-catenin-null cells due to a loss of cell adhesion and the number of expanded cells was reduced. Rescue of β-catenin expression restored adhesion and revealed that the number of NSCs increased in the knockout population. Using a clonal colony-forming assay, which confines precursor cells within a solid collagen matrix, we show that the number of NSCs in the hippocampus is unchanged although the β-catenin knockout striatum actually contains

a larger proportion of NSCs. However, these colonies were smaller than those of control cells, due to increased apoptosis in the progenitor population. Furthermore, β-catenin knockout NSCs also retained multipotentiality as shown by their ability to clonally differentiate into check details neurons and glia. The effects on neural precursor cells were not due to loss of downstream T-cell factor signaling, as this pathway is not active in vivo in regions of the embryonic brain where NSCs and progenitor cells reside, nor is it active in vitro in NSC colonies. These data reveal that β-catenin is not required for the maintenance or differentiation of NSCs, but is required for the MRIP adhesion and survival of neural progenitor cells. “
“The biophysical properties and distribution of voltage-dependent, Ca2+ -modulated K+ (BKCa) currents among subpopulations of acutely dissociated DiI-labeled cutaneous sensory neurons from the adult

rat were characterized with whole-cell patch-clamp techniques. BKCa currents were isolated from total K+ current with iberiotoxin, charybdotoxin or paxilline. There was considerable variability in biophysical properties of BKCa currents. There was also variability in the distribution of BKCa current among subpopulations of cutaneous dorsal root ganglia (DRG) neurons. While present in each of the subpopulations defined by cell body size, IB4 binding or capsaicin sensitivity, BKCa current was present in the vast majority (> 90%) of small-diameter IB4+ neurons, but was present in only a minority of neurons in subpopulations defined by other criteria (i.e. small-diameter IB4−). Current-clamp analysis indicated that in IB4+ neurons, BKCa currents contribute to the repolarization of the action potential and adaptation in response to sustained membrane depolarization, while playing little role in the determination of action potential threshold.

However, relapse is described even among patients with successful

However, relapse is described even among patients with successful treatment and CD4 T-cell counts >200 cells/μL [50]. Cases of leishmaniasis IRIS are described with new or worsening skin lesions including ulcers, mucocutaneous ulcers in the mouth or penis, post-kala-azar dermal leishmaniasis or uveitis [51,52]. There are also reports of visceral leishmaniasis presenting as an immune reconstitution Dapagliflozin phenomenon after the start of antiretroviral therapy [53]. There are

multiple overlapping toxicities with HIV medication and treatment for leishmaniasis and liaison with an HIV pharmacist is recommended. Chagas disease or American trypanosomiasis is caused by a parasite, which is a member of the genus Trypanosoma; Trypanosoma cruzi. It is confined to Central and South America and its distribution extends from Mexico in the north to the northern half of Argentina and Chile in the south. T. cruzi is spread by bloodsucking triatomine insects, also known as kissing bugs, found in particular in rural areas [54]. There is increasing recognition that reactivation of Trypanosoma cruzi infection can cause disease in patients with advanced immunosuppression, including HIV-seropositive individuals who have lived or travelled to endemic areas. T. cruzi causes two main types of disease in people with HIV: Neurological disease; space-occupying lesions or meningoencephalitis Clinical

syndromes are most common in individuals with CD4 T-cell counts <200 cells/μL Talazoparib [55]. Neurological syndromes are the commonest presentation, comprising 75% of presentations of Chagas disease in untreated HIV-seropositive patients. Patients can present with features of a space-occupying lesion, encephalitis, or meningoencephalitis [56]. Clinical symptoms are typically of fever, headaches,

seizures, vomiting and focal neurological signs and mimic toxoplasma encephalitis [54]. Myocarditis is the second most common presentation seen in approximately a third of cases, often with concomitant neurological disease. Myocarditis is often asymptomatic and only detected at autopsy Tacrolimus (FK506) but can present with arrhythmias or heart failure [54,57]. Chagas disease may also affect the digestive tract and cause megaoesophagus or megacolon. Chagas disease should be suspected in patients from the endemic areas of Central and South America or with a history of blood transfusions or intravenous drug use with contacts from these areas. Diagnosis of Chagas disease requires a combination of imaging, serology, PCR and if available histological confirmation (category III recommendation). For neurological disease, imaging studies characteristically report space-occupying lesions similar to those described for toxoplasma encephalitis [58]. CSF examination typically describes lymphocytic pleocytosis and elevated protein with possibly low glucose [54]. Serological tests are generally not diagnostic for reactivation, indicating only previous exposure.

Nevertheless, post-TD IBS remains an issue because it represents

Nevertheless, post-TD IBS remains an issue because it represents a long-term travel sequelae in a previous healthy population. Of

note, the TD-associated IBS incidence is twice the incidence rate of self-limited influenza in a comparable population of travelers. Further investigations need to focus on the pathophysiological interaction of IBS predisposing factors. Research is also needed to optimize TD self-treatment and to determine whether extensive preventive measures, eg, by drug prophylaxis, would reduce the risk of IBS among travelers. If so, those with predisposing Selleck Stem Cell Compound Library factors could in the pre-travel consultation discuss available options to reduce the risk for IBS. The study was self-funded by the Division of Communicable Diseases of the Institute of Social and Preventive Medicine at the University of Zurich, Switzerland. R. S. has obtained research sponsorships

(which could BIBW2992 solubility dmso indirectly be related) from Dr Falk Pharma, Intercell, Optimer, Santarus. Additionally he was sponsered as a speaker by Salix. The other authors state that they have no conflicts of interest to declare. “
“Introduction. Spain could be a potential area in Europe for the development and spread of emerging diseases from the tropics due to its geoclimatic characteristics, but there is little information on infectious diseases imported by travelers. The aim of this article was to analyze clinical–epidemiological characteristics of infectious diseases imported by Spanish travelers Niclosamide from the tropics. Methods. A retrospective descriptive study of 2,982 travelers seeking medical advice who return ill from the tropics was conducted. Demographic data, details of travel (destination, type, and duration), preventive measures, clinical syndromes, and diagnoses were analyzed. Results. Nearly half (46.5%) the travelers had traveled to sub-Saharan Africa; 46.5% reported a stay exceeding 1 month (and almost a quarter more than 6

months). Following pre-travel advice, 69.1% received at least one vaccine and 35.5% took malarial chemoprophylaxis with variations according to geographical area of travel. In all, 58.8% of this took chemoprophylaxis correctly. Most common syndromes were fever 1,028 (34.5%), diarrhea 872 (29.3%), and cutaneous syndrome 684 (22.9%). Most frequent diagnoses were traveler’s diarrhea (17.2%), malaria (17%), and intestinal parasites (10.4%). The three main syndromes in travelers to the Caribbean–Central America, Indian subcontinent–Southeast Asia, and other areas were diarrhea, fever, and cutaneous syndrome (p < 0.05); in sub-Saharan Africa were fever, cutaneous syndrome, and diarrhea (p < 0.05); and in South America were cutaneous syndrome, diarrhea, and fever (p < 0.05). Travelers to sub-Saharan Africa showed a higher frequency of malaria, rickettsiosis, filariasis, and schistosomiasis (p < 0.

After centrifugation at 500 g at 4 °C for 1 min, the beads were a

After centrifugation at 500 g at 4 °C for 1 min, the beads were again gently washed five times with 500 μL cold PBS containing 1% Triton X-100. Fifty microliters of sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) sample buffer was added and the bead solution was then boiled for 1 min. After a final centrifugation at 16 000 g for 1 min at 4 °C, 40 μL was collected for SDS-PAGE. For Western PI3K phosphorylation blot analysis, an anti-c-Myc mouse monoclonal antibody (1 : 1000 dilution, Clontech) and an anti-GFP mouse monoclonal antibody (1 : 5000 dilution, Clontech) were used as the

primary antibodies. A peroxidase-labeled mouse anti-immunoglobulin G antibody (1 : 500 dilution, Vector) was used as the secondary antibody. For the analysis, the primary and secondary antibody reactions were performed for 2 and 1 h, respectively. Approximately 105 conidia were inoculated in 100 μL liquid medium in a glass-based dish, which were then cultured at 30 °C for approximately 20 h. As the cultivation medium, either CD or M [0.2% NH4Cl, 0.1% (NH4)2SO4, 0.05% KCl, 0.05% NaCl, 0.1% KH2PO4, 0.05% XL184 ic50 MgSO4·7H2O, 0.002% FeSO4·7H2O, and 2% glucose, pH 5.5] was used to suit the auxotrophy of each strain.

When required, CD medium was supplemented with 0.0015% Met (CDm). To induce overexpression by the amyB promoter (PamyB), maltose (mal) was used as the sole carbon source. Latrunculin B (Lat B) (Calbiochem) was prepared as a 10 mM solution in dimethyl sulfoxide. N-(3-triethylammoniumpropyl)-4-(p-diethyl-aminophenyl-hexatrienyl)pyridinium dibromide (FM4-64) (Molecular Probes) staining was performed as described previously (Higuchi et al., 2009b). For endocytic recycling analysis, 50 μL culture

medium was removed following FM4-64 staining. The half-time required for apical recycling of FM4-64 to the Spitzenkörper (Spk) was defined as the time when the number of hyphae containing FM4-64-positive Spk Rolziracetam reached half of that at 60 min after staining according to the approximate curve of the graph from the time-course experiment. To search for novel endocytic components in A. oryzae, we conducted YTH screening using AoAbp1 as bait. Using this approach, we identified four genes whose products interacted with AoAbp1. One gene of interest, designated as aipA (DDBJ accession no. AB551525), which was found from only one original clone in the YTH screening, encoded a putative AAA ATPase; the other three genes (aipB-D) will be presented elsewhere. According to the Pfam motif analysis, the deduced amino-acid sequence of AipA contained the AAA ATPase domain and the Vps4 oligomerization domain, which is found at the C-terminal of Vps4, shapes an α-helix structure, and is needed for oligomerization, in the C-terminal region (Fig. 1a). Furthermore, AipA had a single coiled-coil domain in the N-terminal region, suggesting that AipA probably interacts with other proteins through the coiled-coil region (Fig. 1a).

The same five phyla were found in the rhizosphere bacterial commu

The same five phyla were found in the rhizosphere bacterial community structure, although the predominant phylum was different. The Actinobacteria group was the most abundant in the rhizosphere of Fengdan plants, compared

with the Gammaproteobacteria group in the rhizosphere of Lan Furong plants (Tables 1, 2, and Target Selective Inhibitor Library purchase 4; Fig. 1). Among 14 genera in the rhizosphere of the two varieties plant, five genera (Microbacterium, Variovorax, Lysobacter, Sporosarcina, and Bacillus) were found at the same time. The bacterial community structure in the rhizoplane of the two varieties was much more similar than the other two domains in the root of the plants. Both were represented by four phyla with similar percentages. The predominant phylum was also same as Betaproteobacteria. Moreover, members of Bacillus and Pseudomonas were absent at the same time in the rhizoplane of the two varieties of peony. It would appear that a selective pressure of tree peony plants on their associated bacterial populations occurred,

as has been observed before (Lilley et al., 1996; Hallmann et al., 1997). The maximum effects have been seen near the root surface because both are distinct ecological niches where specific nutritional selection PLX-4720 mouse occurs (Marilley & Aragno, 1999; Siciliano & Germida, 1999; Jung et al., 2008). Many isolates were found only in the root of Fengdan or Lan Furong in this study. For example, strains of Agromyces, Arthrobacter, Sphingopyxis, and Cupriavidus were only found in the rhizosphere

of Fengdan, and strains of Cellulosimicrobium, Bosea, Ensifer, and Staphylococcus were only found in rhizosphere of Lan Furong. Strains of Agromyces, Mycobacterium, Sphingopysix, and Sphingobium were only found in the rhizoplane of Fengdan, compared with strains RANTES of Phenylobacterium, Sinorhizobium, and Lysobacter in the rhizoplane of Lan Furong. As the bacterial population densities in the rhizosphere and rhizoplane of Lan Furong were both higher than that of Fengdan, one reasonable explanation is that the host genotypes influenced the distribution pattern of the bacterial community in the root of tree peony plants. A previous study reported that both bacterial and host genotypes influence endophytic colonization (Dong et al., 2003). Further investigations will be necessary to verify whether and how this distribution pattern is mediated by genetic determinants of both partners. Pseudomonas and Bacillus are considered important constituents in the root-associated microbial community, and their ability to colonize the root surface, preventing the development of plant pathogens and improving plant growth, is well known (Rangarajan et al., 2001; Park et al., 2005, 2008; Fett, 2006; Jorquera et al., 2011). We were surprised that no members of these genera were found in the rhizoplane of two tree peony varieties. In fact, no members of Firmicutes were isolated in the rhizoplane.

In loving memory of JL López who died of cancer during the cour

In loving memory of J.L. López who died of cancer during the course of this work. “
“DevR is a key regulator of the dormancy response in Mycobacterium tuberculosis (M. tb). Using DevR as bait to screen a phage display library, a peptide, DevRS1, was obtained. DevRS1 inhibited DevR-regulated transcription and survival of nonreplicating tubercle bacilli in a hypoxia model of dormancy. DevRS1 peptide-mediated inhibition demonstrates the efficacy of intercepting DevR function to block hypoxic adaptation of M. tb. It is estimated that approximately

Pictilisib one-third of the world’s population has latent tuberculosis, a condition in which tubercle bacilli reside in a dormant-like state for indefinite periods of time, sometimes even decades. Individuals with latent infection constitute a potent reservoir for new cases of active disease under conditions of immune

compromise such as in HIV infection and other conditions of diminished immunity. The clearing of dormant organisms in latently infected individuals is a prerequisite for the eradication of TB this website in the community. Dormancy adaptation of tubercle bacteria is associated with the development of an altered physiologic state in which they are more resistant to the action of currently available antitubercular drugs. Therefore, a key challenge in the effective control of TB in the population is to develop drugs that are effective against dormant tubercle bacteria. Two-component systems play a pivotal role in bacterial survival and pathogenesis and have been proposed as novel targets for the development of new antimicrobial agents (Roychoudhury et al., SPTLC1 1998; Macielag & Goldschmidt, 2000; Murphy & Brown, 2007). In Mycobacterium tuberculosis (M. tb), the two-component system DevR-DevS/DosT (also called as DosR-DosS/DosT) mediates the adaptive response to hypoxia, exposure to NO and CO and ascorbic acid under in vitro and ex vivo conditions. These signals are believed to

play a key role in the development of mycobacterial dormancy and latent tuberculosis (Wayne & Sohaskey, 2001; Park et al., 2003; Voskuil et al., 2003, 2004; Kumar et al., 2008; Shiloh et al., 2008; Taneja et al., 2010), suggesting that targeting this signaling pathway may be an effective strategy against dormant tubercle bacilli (Saini & Tyagi, 2005; Murphy & Brown, 2007). Here, we report the successful use of phage display technology to identify a DevR binding peptide, DevRS1, which inhibits DevR-regulated transcription and survival of M. tb under hypoxia. Recombinant DevR protein was overexpressed and purified from Escherichia coli BL21 harboring plasmid pDSR217 (Saini et al., 2004). The Ph.D.-7 phage display peptide library kit (New England Biolabs Inc., Beverely, MA) was screened by biopanning using the manufacturer’s protocol with few modifications. Briefly, five rounds of panning were performed, the first three rounds on agarose beads and the last two in a 24-well polystyrene ELISA plate.

Regardless of the exact effects that Che1 signaling has on cell s

Regardless of the exact effects that Che1 signaling has on cell surface changes which are currently investigated in our laboratory, the data obtained here show that attachment of A. brasilense is increased by nitrogen limitation and further suggests that it depends on sugar-exposed residues that have lectin-binding properties, in agreement with the proposition made previously by Mora et al. (2008). Increasing attachment of A. brasilense to root surfaces may thus ultimately depends on fine-tuning metabolic activities, including limiting nitrogen availability

that is shown here as a key modulator of attachment to surfaces. The authors thank members of MG 132 the Alexandre’s and Doktycz’s laboratory for careful comments on the manuscript. This work was supported by a NSF CAREER award (MCB-0622277) and MCB-0919819 to G.A. and by the Genomic Science Program of the Office of Biological and Environmental Research, US DOE. Oak Ridge National Ku-0059436 mw Laboratory is managed by UT-Battelle, LLC, for the US Department of Energy under Contract no. DE-AC05-00OR22725. “
“The effect of sublethal concentrations

(below the recommended field doses) of propiconazole and tebuconazole on the amount of tri transcripts and accumulation of trichothecenes by three Fusarium graminearum isolates of 3ADON, 15ADON, and NIV chemotypes was examined on yeast extract sucrose agar (YES) medium. RT-qPCR analyses showed higher tri4, tri5, and tri11 transcript levels in cultures of all three F. graminearum isolates supplemented with sublethal concentrations of azoles as compared to those in nontreated control, although the fold changes in the amount of tri transcripts differed according to the type of azole used. Mycotoxin analysis revealed higher increase in trichothecene accumulation in most of the tebuconazole-treated samples of all chemotypes tested. A huge increase in all trichothecene compounds was revealed in samples of all F. graminearum isolates treated with

5 mg L−1 of tebuconazole. An inducing effect of azoles on trichothecene accumulation in the grain was confirmed in an in planta experiment; however, the results obtained were inconsistent. A higher amount of trichothecenes and fungal DNA was quantitated in two grain samples Dipeptidyl peptidase treated with sublethal propiconazole concentrations. In contrast, no significant increase in trichothecene levels was revealed in grain samples treated with sublethal concentrations of tebuconazole. The Fusarium graminearum (teleomorph Gibberella zeae) species complex is one of the most important causal agents of Fusarium head blight (FHB) of wheat and other cereals worldwide (Ward et al., 2008). Fusarium graminearum contaminates the grain with high levels of type B trichothecenes: deoxynivalenol (DON) and nivalenol (NIV) and their acetyl derivatives. Contamination of plant products with these toxins poses a significant risk to food safety and animal health (Foroud & Eudes, 2009). Three major F.

Non-English publications and review articles were also excluded f

Non-English publications and review articles were also excluded from further analysis. The selection process, arriving at a final set of studies for

formal analysis [7-29], is presented in Figure 1. The data were extracted using a standardized form. The following information was extracted from each study: selleck compound author, study design, study period, publication year, follow-up period, sample sizes, disease, comparator groups, outcome measures, estimates, age and geographical location. Details of the selected studies are given in Table 1. Two reviewers independently rated study quality using the Downs and Black checklist [30]. The checklist comprises 27 criteria including subsection of reporting (10), external validity (three) (generalizability of study population), assessment of bias (seven), confounding factors (six) and power (one) of detecting an important clinical effect. We estimated the average quality index score using the checklist based on our 23 observational (21) and randomized (two) studies [13, 26], which resulted in an average score of 15.6 and 19.5 for nonrandomized and randomized studies, respectively,

with a range of 12.5 to 20. We conducted a series of meta-analyses based on similar comparator groups among the studies. The RR of CVD estimated includes: (1) PLHIV who were not on ART compared with HIV-uninfected people; (2) PLHIV who were treated with ART compared with HIV-uninfected people; (3) PLHIV who were treated with ART compared with treatment-naïve PLHIV; and (4) different classes of ART and the duration of treatment. find more The risk estimates extracted from the selected studies were Abiraterone chemical structure from either logistic regression or proportional hazards models with reported confidence intervals. This analysis used estimates where risk was already adjusted for common risk factors such as

age, sex, race, smoking, diabetes and hypertension. The rationale to pool RRs from regression and proportional hazards models was based on the investigation of D’Agostino et al. [31]. D’Agostino et al. demonstrated the asymptotic equivalence of estimating RRs from logistic regression and proportional hazards models. Pooling of RR estimates in this manner has been applied in other analyses (e.g. Lollgen et al. [32]). We calculated the pooled estimates of risks for groups in which there were at least two individual studies. We applied the DerSimonian–Laired (DSL) random effects model [33] to measure the outcome of interest that encounters a heterogeneity effect. We quantified the degree of heterogeneity using the I-squared (I 2) statistic, which can be interpreted as the percentage of total variation across the studies attributable to heterogeneity, and a value of zero indicates no observed heterogeneity [34]. The methodology and reporting of this review conform to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement [35, 36].

Non-English publications and review articles were also excluded f

Non-English publications and review articles were also excluded from further analysis. The selection process, arriving at a final set of studies for

formal analysis [7-29], is presented in Figure 1. The data were extracted using a standardized form. The following information was extracted from each study: Cabozantinib in vitro author, study design, study period, publication year, follow-up period, sample sizes, disease, comparator groups, outcome measures, estimates, age and geographical location. Details of the selected studies are given in Table 1. Two reviewers independently rated study quality using the Downs and Black checklist [30]. The checklist comprises 27 criteria including subsection of reporting (10), external validity (three) (generalizability of study population), assessment of bias (seven), confounding factors (six) and power (one) of detecting an important clinical effect. We estimated the average quality index score using the checklist based on our 23 observational (21) and randomized (two) studies [13, 26], which resulted in an average score of 15.6 and 19.5 for nonrandomized and randomized studies, respectively,

with a range of 12.5 to 20. We conducted a series of meta-analyses based on similar comparator groups among the studies. The RR of CVD estimated includes: (1) PLHIV who were not on ART compared with HIV-uninfected people; (2) PLHIV who were treated with ART compared with HIV-uninfected people; (3) PLHIV who were treated with ART compared with treatment-naïve PLHIV; and (4) different classes of ART and the duration of treatment. http://www.selleckchem.com/products/LBH-589.html The risk estimates extracted from the selected studies were Histamine H2 receptor from either logistic regression or proportional hazards models with reported confidence intervals. This analysis used estimates where risk was already adjusted for common risk factors such as

age, sex, race, smoking, diabetes and hypertension. The rationale to pool RRs from regression and proportional hazards models was based on the investigation of D’Agostino et al. [31]. D’Agostino et al. demonstrated the asymptotic equivalence of estimating RRs from logistic regression and proportional hazards models. Pooling of RR estimates in this manner has been applied in other analyses (e.g. Lollgen et al. [32]). We calculated the pooled estimates of risks for groups in which there were at least two individual studies. We applied the DerSimonian–Laired (DSL) random effects model [33] to measure the outcome of interest that encounters a heterogeneity effect. We quantified the degree of heterogeneity using the I-squared (I 2) statistic, which can be interpreted as the percentage of total variation across the studies attributable to heterogeneity, and a value of zero indicates no observed heterogeneity [34]. The methodology and reporting of this review conform to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement [35, 36].

, 2006; Alexander et al, 2011), while frontal cortical gray matt

, 2006; Alexander et al., 2011), while frontal cortical gray matter volumes do show changes with age in both

species (Alexander et al., 2008, 2011; Shamy et al., 2011). Using a high resolution variant of functional MRI (fMRI) http://www.selleckchem.com/products/chir-99021-ct99021-hcl.html developed to evaluate resting-state metabolism within hippocampal substructures, Small et al. (Small et al., 2002, 2004; Moreno et al., 2007) have shown reduced metabolism in the dentate gyrus of aged mice, monkeys and humans. In animal models, this correlated with memory impairment. Thus, examining activity within hippocampal subregions provides a sensitive method to detect functional changes, even if volume does not differ. Furthermore, it has also been shown that taking individual health into account helps to explain subregion volume differences across age. Shing et al. (2011) report that reduced CA3 and dentate gyrus volume in older adults correlates with memory decline, while reduced volume of the CA1 region correlates with hypertension. Additionally, there is evidence in human samples for age-related signal degradation of white matter in the GDC-0449 manufacturer region of the

perforant pathway (Yassa et al., 2010), the main input to the hippocampus from the entorhinal cortex, reduced white matter volume in this region (Stoub et al., 2012), and dendritic diffusion defects in the dentate gyrus–CA3 region (Yassa et al., 2011). Interestingly, data obtained from electrically-evoked field potential recordings in the dentate gyrus of aged rats (Barnes & McNaughton, 1980; Foster et al., 1991) predicted entorhinal axon collateral pruning. The observation that led to this suggestion was the fact that there was no change in the stimulus current necessary to elicit responses from these axons (i.e., no threshold change), but the maximum amplitude Phosphatidylethanolamine N-methyltransferase of the compound action potential response was reduced in old compared to young rats. Assuming no layer 2 entorhinal cortical cell loss with aging (confirmed in rats: Merrill et al.,

2001; Rapp et al., 2002; and in monkeys: Gazzaley et al., 1997), the reduced maximal amplitude in old rats suggested that there were fewer entorhinal axon collateral fibers running in the perforant pathway. This hypothesis fits rather well with the MRI observation of age-related reductions in perforant path white matter volume in normal aged humans reported by Stoub et al. (2012), but direct counts of entorhinal axon collaterals have yet to be made in aged rats. With the advent of stereological methods, one feature of the aging hippocampus that can be ruled out as significantly contributing to volume or metabolic changes is cell number. That is, cell numbers are preserved in normal aging in the principal cell types of the hippocampus (granule cells, CA1 and CA3 pyramidal cells) in humans (e.g., West et al., 1993), nonhuman primates (e.g., Keuker et al., 2003) and rodents (Rapp & Gallagher, 1996; Rasmussen et al., 1996).