PubMed Health⌕ Search

Biomedical subjects

A Easton

Publications and source records attributed to A Easton.

At least 19 recordsLinked to original sources

Development of signature-tagged mutagenesis in Burkholderia pseudomallei to identify genes important in survival and pathogenesis.

Burkholderia pseudomallei, the causative agent of melioidosis, is an important human pathogen in Southeast Asia and northern Australia for which a vaccine is unavailable. A panel of 892 double signature-tagged mutants was screened for virulence using an intranasal BALB/c mouse model of infection. A novel DNA tag microarray identified 33 mutants as being attenuated in spleens, while 6 were attenuated in both lungs and spleens. The transposon insertion sites in spleen-attenuated mutants revealed genes involved in several stages of capsular polysaccharide biosynthesis and DNA replication and repair, a putative oxidoreductase, ABC transporters, and a lipoprotein that may be important in intercellular spreading. The six mutants identified as missing in both lungs and spleens were found to have insertions in recA involved in the SOS response and DNA repair; putative auxotrophs of leucine, threonine, p-aminobenzoic acid, and a mutant with an insertion in aroB causing auxotrophy for aromatic compounds were also found. Murine challenge studies revealed partial protection in BALB/c mice vaccinated with the aroB mutant. The refined signature-tagged mutagenesis approach developed in this study was used to efficiently identify attenuating mutants from this highly pathogenic species and could be applied to other organisms.

Animals↗

Estradiol and orexin-2 saporin actions on multiple forms of behavioral arousal in female mice.

Estrogens modulate almost all aspects of female behavioral arousal; however, apart from that of sexual behavior, the neurobiology of female arousal remains unclear. Because orexins-hypocretins are neurotransmitters known to be important for behavioral arousal, the authors hypothesized that orexins may be a target for estrogen. Gonadectomized female mice received an intracerebral injection of either phosphate-buffered saline, the neurotoxin saporin (SAP), or the orexin-2-saporin conjugate (OXSAP) in the lateral hypothalamus. SAP- and OXSAP-treated mice were also divided into groups receiving either estradiol capsules or oil capsules. Mice were tested in 3 behavioral tests measuring different modes of arousal: sensory responsiveness, running wheel activity, and fearfulness. OXSAP mice showed decreases in sensory responsiveness and fearfulness concomitant with a reduction in orexin cell number. Estradiol affected all behaviors tested but decreased fearfulness only when combined with OXSAP treatment. These data indicate that estrogens modulate orexins' effects on fearfulness.

Animals↗

Acute estrogen potentiates excitatory responses of neurons in rat hypothalamic ventromedial nucleus.

In a previous behavioral study, brief application of a membrane-limited estrogen to neurons in rat hypothalamic ventromedial nucleus (VMN) facilitated lordosis behavior-inducing genomic actions of estrogen. Here, electrophysiological recordings from single neurons were employed to characterize these membrane-initiated actions. From rat hypothalamic slices, electrical activity was recorded from neurons in the ventrolateral VMN, the cell group crucial for estrogen induction of lordosis. In addition to the resting activity, neuronal responses to histamine (HA) and N-methyl-d-aspartate (NMDA) were also recorded before, during, and after a brief (10-15 min) application of estradiol (E, 10 nM). These two transmitters were chosen because their actions are mediated by different mechanisms: HA through G protein-coupled receptors and NMDA by ligand-activated ion channels. Vehicle applications did not affect either resting activity or neuronal responses. In contrast, acute E exposure modulated neuronal responses to transmitters, with no significant effect on the resting activity. It potentiated excitatory responses to HAs (20 out of 48 cells tested) and to NMDA (10 out of 19 cells), but attenuated inhibitory responses to HA (3 out of 6 units). Both of these hormonal actions would increase VMN neuronal excitation. In separate experiments, neuronal excitation was found to be suppressed by anesthetics, which would block E's induction of lordosis when administered at the time of estrogen application. These data are consistent with the notion that increasing electrical excitation of VMN neurons can be a mechanism by which acute E exposure facilitates the lordosis-inducing genomic actions of estrogens.

Animals↗

Sex differences in mouse behavior following pyrilamine treatment: role of histamine 1 receptors in arousal.

Arousal, the activation of brain and behavior, is a fundamental component of behavior. While sex differences in behavior are pervasive, it is unknown whether they could be due to an underlying dimorphism in arousal mechanisms. Because histamine (HA) acting through histamine 1 (H1) receptors is one essential component of arousal neural circuitry, the aim of the current experiment was to measure sex differences in behavioral arousal following treatment with the H1 receptor antagonist, pyrilamine (PYRL). Castrated male and ovariectomized female Swiss-Webster mice were treated subcutaneously with either 15 or 35 mg/kg of PYRL. The effect of drug treatment was determined in an array of behaviors: sensory responsiveness, running wheel activity, and fearfulness. Surprisingly, the lower dose of PYRL increased some aspects of arousal, sensory responsiveness, and anxiety-like behavior, while the higher dose of PYRL resulted in decreases in arousal across tests, indicating that antagonism of histamine receptors does not have a linear relationship with arousal. Females were more sensitive to the arousal-reducing effects of PYRL than males in sensory and running wheel tasks but not in tests of emotion. In conclusion, antagonism of H1 receptors can alter arousal in a sex-dependent manner, independent of circulating gonadal steroids, in mice.

Animals↗

Budapest Student Health Behavior Survey--Budapest, Hungary, 1999. Findings on unintentional and intentional injuries, alcohol use, and sexual activity.

OBJECTIVE: In Hungary, a large proportion of adult morbidity and mortality can be attributed to health risk behaviors that begin in early adolescence. To date, studies examining health risk behaviors among youth have rarely been undertaken in Hungary. In order to expand current research in this area, the Hungarian Metropolitan Institute of State Public Health and Public Health Officer Service and the Office on Smoking and Health at the U.S. Centers for Disease Control and Prevention developed and implemented the Budapest Student Health Behavior Survey. The objective of this study was to examine health behavior risk factors among secondary school students in Budapest in 1999. METHODS: The 1999 Budapest Student Health Behavior Survey is cross-sectional school-based survey A 2-stage cluster sampling design was used to produce a representative sample of secondary students in grades 9-12 in Budapest. Information was collected on unintentional and intentional injuries, alcohol use, and sexual activity. FINDINGS: During the 30 days preceding the survey, 28.7% of students had rarely or never worn a seatbelt and 68.1% drunk alcohol. During the 12 months preceding the survey, 14.5% had been threatened or injured with a weapon, 12.9% experienced dating violence, and 13.5% seriously considered suicide. Of the 44.7% of students who had had sexual intercourse, 29.5% had > or = 4 sex partners. Of sexually active students, 50.4% had not used a condom at last sexual intercourse. CONCLUSION: Many secondary school students in Budapest practice behaviors that place them at risk for serious health problems both in the short and long-term. Programs and policies that adequately address such behaviors among secondary school students are needed to reduce subsequent morbidity and mortality.

Adolescent↗

Behaviour of marmoset monkeys in a T-maze: comparison with rats and macaque monkeys on a spatial delayed non-match to sample task.

The marmoset ( Callithrix jacchus) is a small New World monkey that is increasingly being used in a laboratory setting. A previous set of studies has provided a direct comparison between the performance of rats and macaque monkeys on a spatial delayed non-match to sample task in a T-maze (Murray et al. 1989, Experimental Brain Research 74:173-186; Markowska et al. 1989, Experimental Brain Research 74:187-201). In the current experiment we replicated these studies using the marmoset. This allowed for a comparison of the behavioural performance of the marmoset with both rats and macaque monkeys. Marmosets performed well at the task, performing better than macaques, and at a similar level to rats. A closer analysis of the data from the present experiment suggests that marmosets spontaneously alternated in the T-maze, a strategy often adopted by rats, but not by macaques in the T-maze.

Animals↗

The circadian Clock mutation increases exploratory activity and escape-seeking behavior.

Disturbances of circadian rhythms are associated with many types of mood disorders; however, it is unknown whether a dysfunctional circadian pacemaker can be the primary cause of altered emotional behavior. To test this hypothesis, male and female mice carrying a mutation of the circadian gene, Clock, were compared to wild-type mice in an array of behavioral tests used to measure exploratory activity, anxiety, and behavioral despair. Female Clock mutant mice exhibited significantly greater activity and rearing in an open field and a greater number of total arm entries in the elevated plus maze. In addition, female Clock mutant mice spent significantly more time swimming in the forced swim test than wild-type mice on both days of a 2-day test. Male Clock mutant mice also exhibited increased exploration of the open field and increased swimming in the forced swim test; however, behavioral changes were less robust in Clock mutant males compared to Clock mutant females. These changes in behavior were not dependent on the expression of a lengthened free-running period but were more or less striking depending on the testing conditions. These data indicate that the Clock mutation leads to increased exploratory behavior and increased escape-seeking behavior, and, conversely, does not result in increased anxiety or depressive-like behavior. These results suggest that the Clock gene is involved in regulating behavioral arousal, and that Clock may interact with sex hormones to produce these behavioral changes.

Animals↗

Unilateral lesions of the cholinergic basal forebrain and fornix in one hemisphere and inferior temporal cortex in the opposite hemisphere produce severe learning impairments in rhesus monkeys.

It has been proposed that isolation of the inferior temporal cortex and medial temporal lobe from their cholinergic afferents results in a severe anterograde amnesia. To test this hypothesis directly, seven rhesus monkeys received a unilateral immunotoxic lesion of the cholinergic cells of the basal forebrain with an ipsilesional section of the fornix. In a second surgery, inferior temporal cortex was ablated in the opposite hemisphere. All animals were severely impaired at learning visual scenes and object-reward associations. The impairment in learning scenes was correlated with cholinergic cell loss in the basal forebrain, but not with generalized tissue damage. Two monkeys served as surgical controls with saline injection in place of the immunotoxin, but all other procedures the same, and were not as severely impaired as those with immunotoxic lesions. Previous work has shown that monkeys with bilateral section of the anterior temporal stem (white matter of the temporal lobe), amygdala and fornix show a severe new learning impairment, and provide a model of human medial temporal lobe amnesia. One effect of this combined ablation is to isolate inferior temporal cortex and medial temporal lobe from their cholinergic afferents, possibly in addition to a direct disruption of the hippocampal system. The results of the present study, then, provide a novel link between the mechanisms of medial temporal lobe amnesia and Alzheimer's disease in which the cholinergic basal forebrain shows pathology. We propose that in both cases the mnemonic impairments result from isolating inferior temporal cortex and medial temporal lobe from their cholinergic afferents, possibly in addition to a direct disruption of the hippocampal system.

Acetylcholine↗

Toxicity of the dithiocarbamate fungicide mancozeb to the nontarget soil nematode, Caenorhabditis elegans.

We have previously shown that the dithiocarbamate fungicide, Mancozeb, strongly induces lacZ reporter expression from an endogenous heat-shock promoter (hsp16) in the PC72 transgenic strain of the nematode Caenorhabditis elegans. Such evidence of organismal stress, in a nontarget species at subapplication concentrations, was much less apparent for the related fungicide, Maneb, which only weakly induced reporter expression. We now show that reporter induction by Mancozeb is marginal (<60%) after a few hours' exposure, but increases substantially (to almost 10-fold) after overnight exposure. In conjunction with our previous results using intermediate exposure periods, this suggests that the factor limiting reporter responses is likely to be a slow rate of uptake and/or metabolism of the fungicide. We confirm that a potentially toxic metabolite of dithiocarbamate fungicides, namely ethylenethiourea (ETU), has minimal toxicity toward C. elegans, even after prolonged exposure at high concentrations. We demonstrate that exposure to Mancozeb (but not ETU) significantly inhibits larval growth in C. elegans, although this parameter is not markedly more sensitive than reporter induction as a toxicological endpoint. Finally, we have used two-dimensional electrophoresis to show that high concentrations of both Maneb and Mancozeb drastically simplify the protein spot profile compared with controls. However, only in the latter case is there evidence of novel proteins being induced. Both fungicides appear toxic to C. elegans, but only Mancozeb induces a strong heat-shock response.

Animals↗

Dense amnesia in the monkey after transection of fornix, amygdala and anterior temporal stem.

The traditional explanation of dense amnesia after medial temporal lesions is that the amnesia is caused by damage to the hippocampus and related structures. An alternative view is that dense amnesia after medial temporal lesions is caused by the interruption of afferents to the temporal cortex from the basal forebrain. These afferents travel to the temporal cortex through three pathways, namely the anterior temporal stem, the amygdala and the fornix-fimbria, and all these three pathways are damaged in dense medial temporal amnesia. In four experiments using different memory tasks, we tested the effects on memory of sectioning some or all of these three pathways in macaque monkeys. In a test of scene-specific memory for objects, which is analogous in some ways to human episodic memory, section of fornix alone, or section of amygdala and anterior temporal stem sparing the fornix, each produced a significant but mild impairment. When fornix section was added to the section of anterior temporal stem and amygdala in this task, however, a very severe impairment resulted. In an object recognition memory task (delayed matching-to-sample) a severe impairment was seen after section of anterior temporal stem and amygdala alone, with or without the addition of fornix section; this impairment was significantly more severe than that which was seen in the same task after amygdalectomy leaving the temporal stem intact, with or without fornix section. Animals with combined section of anterior temporal stem, amygdala and fornix were also impaired in object-reward association learning. However, the retention of pre-operatively acquired object-reward associations was at a high level. These results show that the pattern of impairments after section of anterior temporal stem, amygdala and fornix in the monkey, leaving hippocampus intact, resembles human dense amnesia and is different from the effects of hippocampal lesions in the monkey.

Amnesia↗

Crossed unilateral lesions of the medial forebrain bundle and either inferior temporal or frontal cortex impair object-reward association learning in Rhesus monkeys.

In an accompanying paper we showed that combined transection of the fornix, amygdala and temporal stem in monkeys produced dense amnesia, including an impairment in visual object-reward association learning. We proposed that this combined surgical section had its effect by isolating temporal cortex from the ascending projections of the basal forebrain and midbrain structures. To test this hypothesis, in the present experiment we disconnected the inferior temporal cortex from these basal forebrain and midbrain structures, while sparing cortical white matter, by crossed unilateral lesions of the medial forebrain bundle in one hemisphere and inferior temporal cortex in the opposite hemisphere. The aim of the medial forebrain bundle lesion was to section axons of cells, both those that project to the cortex via the medial forebrain bundle, and those which control the activity of these same structures. A single unilateral lesion alone had no effect on the ability to learn and remember visual object-reward associations, but the crossed unilateral lesions produced an impairment in this task which was equal in severity to the impairment seen earlier after bilateral section of the fornix, amygdala and temporal stem. The impairment was not an effect of interrupting fibres to the cortex from the ventromedial hypothalamus, or of unilateral sensory neglect. This supports the hypothesis that these midbrain and basal forebrain afferents to the inferior temporal cortex are important for new visual learning. Furthermore, an impairment of equal severity was demonstrated in a separate group of animals that received crossed unilateral lesions of the medial forebrain bundle in one hemisphere and of the frontal cortex in the opposite hemisphere. We propose that the frontal cortex acts to modulate basal forebrain activity which in turn reinforces object representations in the inferior temporal cortex during learning.

Animals↗

Crossed unilateral lesions of medial forebrain bundle and either inferior temporal or frontal cortex impair object recognition memory in Rhesus monkeys.

In monkeys, section of the fornix, amygdala and anterior temporal stem results in a severe anterograde amnesia. Immunolesions of the cholinergic cells of the basal forebrain suggest that this amnesia is a result of isolating the inferior temporal cortex and medial temporal lobe from their cholinergic basal forebrain afferents. In this experiment, six monkeys were trained in a delayed match-to-sample task and then received a section of the medial forebrain bundle in one hemisphere and an ablation of either the frontal or inferior temporal cortex in the opposite hemisphere. All the animals were severely impaired in the performance of this task following this surgery, and the severity of the impairment was independent of the cortical area from which the medial forebrain bundle was disconnected. These results support a model of fronto-temporal interaction via the basal forebrain in new learning, in which midbrain sites related to reward modulate the cholinergic basal forebrain activity.

Animals↗

Smoking among lesbians, gays, and bisexuals: a review of the literature.

OBJECTIVES: To collect estimates of smoking prevalence among lesbian, gay, and bisexual people from the published literature and to compare with general population estimates. METHODS: Databases were searched for all studies published in English on tobacco use among lesbians, gays, and bisexuals. From 1987 through 2000, twelve studies were identified (four youth, eight adult): seven were based on convenience samples; one on a population-based probability sample; one involved random sampling within selected census tracts; one was based on a large multicenter clinical trial; and two were representative school-based samples. Study findings were compared to national survey data from the corresponding time period. RESULTS: Estimated smoking rates for lesbians, gays, and bisexuals ranged from 38% to 59% among youth and from 11% to 50% among adults. National smoking rates during comparable periods ranged from 28% to 35% for adolescents and were approximately 28% for adults. CONCLUSIONS: While information in the published literature is limited, it appears that smoking rates are higher among adolescent and adult lesbians, gays, and bisexuals than in the general population. Steps should be taken to ensure representation of lesbians, gays, and bisexuals in tobacco-use surveillance and to collect data in order to understand the apparent high smoking rates in these groups. Attempts should be made to target prevention and cessation interventions to lesbians, gays, and bisexuals.

Adolescent↗

Restraint increases prolactin and REM sleep in C57BL/6J mice but not in BALB/cJ mice.

Sleep is generally considered to be a recovery from prior wakefulness. The architecture of sleep not only depends on the duration of wakefulness but also on its quality in terms of specific experiences. In the present experiment, we studied the effects of restraint stress on sleep architecture and sleep electroencephalography (EEG) in different strains of mice (C57BL/6J and BALB/cJ). One objective was to determine if the rapid eye movement (REM) sleep-promoting effects of restraint stress previously reported for rats would also occur in mice. In addition, we examined whether the effects of restraint stress on sleep are different from effects of social defeat stress, which was found to have a non-REM (NREM) sleep-promoting effect. We further measured corticosterone and prolactin levels as possible mediators of restraint stress-induced changes in sleep. Adult male C57BL/6J and BALB/cJ mice were subjected to 1 h of restraint stress in the middle of the light phase. To control for possible effects of sleep loss per se, the animals were also kept awake for 1 h by gentle handling. Restraint stress resulted in a mild increase in NREM sleep compared with baseline, but, overall, this effect was not significantly different from sleep deprivation by gentle handling. In contrast, restraint stress caused a significant increase in REM sleep compared with handling in the C57BL/6J mice but not in BALB/cJ mice. Corticosterone levels were significantly and similarly elevated after restraint in both strains, but prolactin was increased only in the C57BL/6J mice. In conclusion, this study shows that the restraint stress-induced increase in REM sleep in mice is strongly strain dependent. The concomitant increases in prolactin and REM sleep in the C57BL/6J mice, but not in BALB/cJ mice, suggest prolactin may be involved in the mechanism underlying restraint stress-induced REM sleep. Furthermore, this study confirms that different stressors differentially affect NREM and REM sleep. Whereas restraint stress promotes REM sleep in C57BL/6J mice, we previously found that in the same strain, social defeat stress promotes NREM sleep. As such, studying the consequences of specific stressful stimuli may be an important tool to unravel both the mechanism and function of different sleep stages.

Animals↗

Smoking cessation counseling by primary care women physicians: Women Physicians' Health Study.

OBJECTIVES: The Women Physicians' Health Study (WPHS) offers a unique opportunity to examine the counseling and screening practices of women physicians. The objectives of this study were to: describe the prevalence of self-reported smoking cessation counseling among primary care women physicians and determine the association between physician demographic, professional, and personal characteristics and smoking cessation counseling. METHODS: Conducted in 1993-1994, WPHS is a nationally representative cross-sectional mailed survey of U.S. women physicians and included 4,501 respondents representing all major specialties. Primary care physicians included 5 specialty areas and were grouped into 3 categories: (1) general primary care; (2) obstetrics/gynecology (ob/gyn); and (3) pediatrics. Frequent counseling was defined as having counseled patients who were known smokers at every visit or at least once a year. RESULTS: Women physicians in general primary care (84%) and ob/gyn (83%) were more likely to frequently counsel their patients about cessation than were pediatricians (41%). Perceived relevance of counseling to a physician's practice was significantly associated with frequent counseling. Personal characteristics (current smoking status, personal or family history of a smoking-related disease, or living with a smoker as an adult or child) were not significantly correlated with counseling. CONCLUSION: The majority (71%) of physicians reported frequently counseling their patients. However, there was significant variation by physician specialty. In addition, perceived relevance of counseling was strongly associated with counseling behavior. Physician counseling on cessation can reduce tobacco-related morbidity and mortality. Increasing perceived relevance, implementing system changes, and creating accountability can facilitate cessation counseling by physicians.

Adult↗

Non-primary care physicians and smoking cessation counseling: Women Physicians' Health Study.

OBJECTIVES: The Women Physicians' Health Study (WPHS) offers a unique opportunity to examine the counseling and screening practices of women physicians in various specialties. In this study we describe the prevalence of self-reported counseling on smoking cessation among non-primary care women physicians and examine the association between their demographic, professional, and personal characteristics and such counseling on smoking cessation. METHODS: Conducted in 1993-1994, WPHS is a nationally representative cross-sectional mailed survey of U.S. women physicians with 4,501 respondents representing all major specialties. Physicians in 9 specialty areas were grouped in 6 categories: (1) anesthesiology; (2) general surgery and surgical subspecialties; (3) emergency medicine; (4) medical subspecialties; (5) psychiatry; and (6) other. Frequent counseling was defined as having counseled patients who were known smokers at every visit or at least once a year. RESULTS: Overall, 45% of the physicians frequently counseled smokers to quit. Medical subspecialists (80%) were most likely and psychiatrists (29%) least likely to counsel frequently. Specialty, perceived relevance of counseling to the physician's practice, and self-confidence in counseling about smoking cessation were associated with frequent counseling. CONCLUSION: Cessation counseling by non-primary care physicians can reduce tobacco-related morbidity and mortality. Increasing perceived relevance and self-confidence among this group of physicians, combined with implementation of system changes and the creation of physician accountability can facilitate the provision of such counseling.

Adult↗

Emergence of a new Vibrio parahaemolyticus serotype in raw oysters: A prevention quandary.

CONTEXT: In May and June 1998, reported Vibrio parahaemolyticus infections increased sharply in Texas. OBJECTIVE: To determine factors that contributed to the increase in V parahaemolyticus infections. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional survey of persons reporting gastroenteritis after eating seafood in Texas; survey of environmental conditions in Galveston Bay. MAIN OUTCOME MEASURES: Traceback of oysters, water quality measures in harvest areas, presence of V parahaemolyticus in stool cultures; comparison of median values for environmental conditions before and during the outbreak compared with during the previous 5 years. RESULTS: Between May 31 and July 10, 1998, 416 persons in 13 states reported having gastroenteritis after eating oysters harvested from Galveston Bay. All 28 available stool specimens from affected persons yielded V parahaemolyticus serotype O3:K6 isolates. Oyster beds met current bacteriologic standards during harvest and fecal coliform counts in water samples were within acceptable limits. Median water temperature and salinity during May and June 1998 were 30.0 degrees C and 29.6 parts per thousand (ppt) compared with 28.9 degrees C and 15.6 ppt for the previous 5 years (P<.001). CONCLUSIONS: This is the first reported outbreak of V parahaemolyticus serotype O3:K6 infection in the United States. The emergence of a virulent serotype and elevated seawater temperatures and salinity levels may have contributed to this large multistate outbreak of V parahaemolyticus. Bacteriologic monitoring at harvest sites did not prevent this outbreak, suggesting that current policy and regulations regarding the safety of raw oysters require reevaluation. Consumers and physicians should understand that raw or undercooked oysters can cause illness even if harvested from monitored beds. In patients who develop acute gastroenteritis within 4 days of consuming raw or undercooked oysters, a stool specimen should be tested for Vibrio species using specific media. JAMA. 2000;284:1541-1545.

Animals↗

Comparison of perirhinal cortex ablation and crossed unilateral lesions of the medial forebrain bundle from the inferior temporal cortex in the rhesus monkey: effects on learning and retrieval.

Seven monkeys learned new object-reward associations and scene problems and were overtrained on 100 problems of each type. Four monkeys received crossed lesions of the medial forebrain bundle (MFB) and inferior temporal cortex, with the later addition of a fornix section ipsilateral to the MFB lesion. The remaining 3 monkeys received bilateral perirhinal cortex ablation. Disconnection of the MFB from the inferior temporal cortex impaired postoperative new learning, but the retrieval of problems overtrained preoperatively was relatively preserved. Subjects with perirhinal cortex ablation were severely impaired in new learning and at the retrieval of scene problems, but retention of object-reward associations was relatively well preserved. The results support the hypothesis that isolation of the inferior temporal cortex from basal forebrain and midbrain afferents results in dense anterograde amnesia, whereas the role of the perirhinal cortex in learning is dependent on the perceptual difficulty of the task.

Amygdala↗