Finding a goal on dry land and in the water: differential effects of disorientation on spatial learning.

Two previous studies, Martin et al. (J. Exp.

Dorsal/ventral hippocampus, fornix, and conditioned place preference.

Conditioned place preference (CPP) is a learning paradigm requiring formation of associations between reward and particular locations. White and McDonald (Behav Brain Res 1993;55:269-281) demonstrated that amygdala (AMG) lesions impair, while fornix (Fx) lesions enhance learning of this task. In the present experiments, we replicated the effects of AMG and Fx lesions, but we also found that complete hippocampal (HPC) lesions interfere with normal performance.

Context-specific interference on reversal learning of a stimulus-response habit.

Learning occurs in a particular place and time. In most learning situations, information about the training context is encoded along with the task demands and solution. However, the extent to which context contributes to the acquisition and expression of a particular learned response is unclear.

A cautionary note on interpreting the effects of partial reinforcement on place learning performance in the water maze.

The effects of partial reinforcement on dry land and swimming pool place learning tasks have recently been compared and it has been suggested that they differ fundamentally [8]. That is, partial reinforcement impairs performance in the water maze, but not on dry land. However, other evidence suggests that partial reinforcement may have the opposite effect in the water maze, strengthening the accuracy and persistence of spatial responses.

Circadian phase-shifted rats show normal acquisition but impaired long-term retention of place information in the water task.

It is thought that circadian rhythms may influence learning and memory processes. However, research supporting this view does not dissociate a mnemonic impairment from other performance deficits. Furthermore, published reports do not specify the type of memory system influenced by the circadian system.

Circadian rhythms, aging and memory.

In human beings and animal models, cognitive performance is often impaired in natural and experimental situations where circadian rhythms are disrupted. This includes a general decline in cognitive ability and fragmentation of behavioural rhythms in the aging population of numerous species. There is some evidence that rhythm disruption may lead directly to cognitive impairment; however, this causal link has not been made for effects due to aging.

Trafficking of neutrophils across airway epithelium is dependent upon both thioredoxin- and pertussis toxin-sensitive signaling mechanisms.

Leukocyte recruitment from the circulation into the airways is a multi-step process, involving both chemotactic and adhesive mechanisms. Using an in vitro model of leukocyte transepithelial trafficking, we show that movement of human peripheral blood neutrophils (PMN) across airway epithelium in the optimal basolateral-to-apical surface direction is partially blocked by pertussis toxin, an inhibitor of G(alphai)-protein-linked receptors. A neutralizing monoclonal antibody against interleukin-8 (IL-8; constitutively expressed by airway epithelium) did not inhibit PMN transepithelial migration, suggesting that alternative pertussis toxin-sensitive signaling mechanisms are involved in this process.

Circadian rhythms, aging and memory.

In human beings and animal models, cognitive performance is often impaired in natural and experimental situations where circadian rhythms are disrupted. This includes a general decline in cognitive ability and fragmentation of behavioural rhythms in the aging population of numerous species. There is some evidence that rhythm disruption may lead directly to cognitive impairment; however, this causal link has not been made for effects due to aging.

Rats with hippocampal damage are impaired on place learning in the water task when overtrained under constrained conditions.

To date, numerous investigations have been conducted on the mammalian hippocampus to determine its precise function. This research has implicated a fundamental role for the hippocampus in the formation of a spatial map that an animal can use to appropriately guide behavior in complex relational tasks. Despite substantial evidence to support this view, there have been challenges to this theory of hippocampal function.

Amygdala, hippocampus and discriminative fear conditioning to context.

Various measures of fear have been shown to condition to a fearful context with different acquisition rates (Antoniadis EA, McDonald RJ. Fear conditioning to context expressed by multiple measures of fear in the rat, Behav Brain Res 1999;101(1):1-14). Freezing, locomotion, urination and preference are 'fast' measures of fear in that they discriminatively condition to context after a single training session, while ultrasonic vocalizations and defecation are 'slow' measures of fear given that they condition following three training sessions.

Neutrophils enhance clearance of necrotic epithelial cells in ozone-induced lung injury in rhesus monkeys.

To test the hypothesis that neutrophil influx is important for the removal of necrotic airway epithelial cells, rhesus monkeys were treated with a function-blocking monoclonal antibody (MAb) against CD18 followed by exposure to ozone or filtered air. CD18 MAb-treated, ozone-exposed monkeys showed a significant inhibition of neutrophil emigration and an accumulation of necrotic airway epithelial cells. In a subsequent experiment, monkeys were given CD18 MAb or an isotype control immunoglobulin before ozone or filtered-air exposure.

Substance P primes the formation of hydrogen peroxide and nitric oxide in human neutrophils.

Substance P (SP), a neurotransmitter of the central and peripheral nervous system, has been implicated as a mediator of the pulmonary inflammatory response through its stimulatory effects on neutrophils. We investigated the role of SP in priming the production of reactive oxygen species by human neutrophils with the cytochrome c reduction assay and by flow cytometry using the intracellular oxidizable probe dichlorofluorescein. We also investigated SP-induced formation of nitrite and nitrate as an index of nitric oxide (NO) production.

Bone SPECT of the back after lumbar surgery.

Purpose: It may be difficult to evaluate back pain in patients who have undergone spinal surgery, because symptoms may be secondary to all the possible abnormalities in patients who have not had surgery plus postoperative complications, including infection, unstable fusion sites, or transfer of biomechanical stresses to other regions.

Materials And Methods: Sixty-three patients with back pain and a history of lumbar spinal surgery had bone SPECT examinations. Twenty-eight patients had laminectomies, 10 had laminectomies with fusion, 10 had laminectomies with fusion and metallic stabilization devices (3 of which were removed), 7 had fusion without laminectomy, 7 had discectomies, and 1 had a fusion with metallic stabilization but no laminectomy.

Lesions of the medial or lateral perforant path have different effects on hippocampal contributions to place learning and on fear conditioning to context.

The axons of the neurons in the medial and lateral components of the entorhinal cortex (MEC and LEC) form the medial and lateral perforant paths (MPP and LPP) which represent the major source of cortical input to the hippocampus. Anatomical, physiological, and pharmacological studies have shown that MPP and LPP are distinct. Unfortunately, assessment of the functional significance of damage to either of these pathways has not used tasks known to be sensitive to hippocampal function in the rodent.

Discriminative fear conditioning to context expressed by multiple measures of fear in the rat.

There has been a renewed interest in the neural basis of fear conditioning to context. These current approaches are accompanied by some limitations including the use of short testing windows, non-discriminative paradigms, and unitary fear response assessment. In an attempt to circumvent these limitations, a discriminative context procedure assessing multiple response measures of fear was used in the present study.

Effects of medial and lateral caudate-putamen lesions on place- and cue-guided behaviors in the water maze: relation to thigmotaxis.

Rats with dorsomedial or dorsolateral caudate-putamen lesions and sham-operated controls were trained on the standard hidden platform (place) task in the water maze. Compared to controls, rats with dorsomedial, but not dorsolateral lesions were slower to escape to the hidden platform and spent significantly more time swimming near the wall of the pool (thigmotaxis) on the early trials, but eventually achieved control levels of performance. When the platform was removed from the pool, all groups exhibited a significant bias for swimming in the training quadrant and crossing the former location of the platform.

Neutrophils injure bronchial epithelium after ozone exposure.

Neutrophil (PMN) influx is an early, prominent finding in the airways of humans after experimental inhalation of ozone (O3), however the potential for PMN to contribute to epithelial injury in this setting is unknown. Bronchial epithelial cells of the human BEAS 2B R1.4 cell line or primary human bronchial epithelial cells underwent DNA labeling by incubation with BrdU.

The dorsal hippocampus is essential for context discrimination but not for contextual conditioning.

The authors describe how (a) the timing of hippocampal lesions and (b) the behavioral-representational demands of the task affect the requirement for the hippocampus in contextual fear conditioning. Post- but not pretraining lesions of the hippocampus greatly reduced contextual fear conditioning. In contrast, pretraining lesions of the hippocampus abolished context discrimination, a procedure in which mice are trained to discriminate between 2 similar chambers (shock context vs.

Aerosol delivery of lipid:DNA complexes to lungs of rhesus monkeys.

Purpose: The potential use of aerosol delivery for non-viral gene therapy was tested by nebulization of lipid:DNA complexes to the lungs of rhesus monkeys.

Methods: Four female rhesus monkeys were dosed with lipid:DNA formulations via aerosol inhalation, where the DNA coded for the human Cystic Fibrosis Transmembrane Conductance Regulator (hCFTR) protein. Delivery of DNA was determined in lung samples by polymerase chain reaction (PCR) by qualitative and quantitative methods.

Lesions of the hippocampus or fornix do not interfere with the relative validity effect on a discrete stimulus or the context.

Two experiments with rats used an appetitively motivated instrumental discrimination procedure to examine whether damage to the hippocampal system would interfere with the relative validity effect in which a partially reinforced stimulus trained in compound acquires a weak conditioned response when concurrently trained CSs are perfect predictors of the presence or absence of the US [A.R. Wagner, F.

Hypoxic regulation of endothelial glyceraldehyde-3-phosphate dehydrogenase.

The glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is induced by hypoxia in endothelial cells (EC). To define the mechanisms by which GAPDH is regulated by hypoxia, EC were exposed to cobalt, other transition metals, carbon monoxide (CO), deferoxamine, or cycloheximide in the presence or absence of hypoxia for 24 h, and GAPDH protein and mRNA levels were measured. GAPDH was induced in cells by the transition metals cobalt, nickel, and manganese and by deferoxamine, and GAPDH mRNA induction by hypoxia was blocked by cycloheximide.

Mycobacterium tuberculosis miniepidemic in a church gospel choir.

Background: Conventional contact investigation and molecular fingerprinting of Mycobacterium tuberculosis isolates in tuberculosis (TB) outbreaks have facilitated recognition as well as application of public health control activities. Singing in a choir as an activity that promotes TB transmission has been occasionally recognized. Such avocational transmission in a middle class community can occur with attendant difficulties encountered in contact investigation.

Safety of airway gene transfer with Ad2/CFTR2: aerosol administration in the nonhuman primate.

In this study, the safety and efficacy of aerosol delivery to non-human primates of an adenoviral vector encoding the cystic fibrosis transmembrane conductance regulator protein (CFTR) were evaluated. The technique of concurrent flow spirometry was used to determine the deposited dose of Ad2/CFTR-2, which ranged from 3 to 8 x 10(10) I.U.

Systematic comparison of the effects of hippocampal and fornix-fimbria lesions on acquisition of three configural discriminations.

The effects of lesions to the hippocampal system on acquisition of three different configural tasks by rats were tested. Lesions of either the hippocampus (kainic acid/colchicine) or fornix-fimbria (radiofrequency current) were made before training. After recovery from surgery, rats were trained to discriminate between simple and compound-configural cues that signaled the availability or nonavailability of food when a bar was pressed.

Prenatal exposure to moderate levels of ethanol can have long-lasting effects on hippocampal synaptic plasticity in adult offspring.

Prenatal ethanol exposure has been associated with long-lasting intellectual impairments in children. Previous studies using animal models of fetal ethanol exposure suggest that these deficits are, at least in part, linked to neurochemical abnormalities in the hippocampal formation. We explored whether prenatal exposure to moderate quantities of ethanol produced functional deficits at the entorhinal cortical perforant path-dentate granule cell connection by examining some electrophysiological properties, including the induction of long-term potentiation (LTP).