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Evaluation of bioaerosol exposures during conditioning of biofilter organic media beds.

Biological media air filters (biofilters) are currently being used for the treatment of inorganic and organic gases from sewage treatment plants, industrial processes, and remediation systems. The media may be organic material such as compost, wood chips, or synthetic plastic media, each with a large surface area for microorganism growth and activity. An occupational health and safety graduate student team (OHS team) evaluated potential particulate and bioaerosol exposure from a biofilter unit process used to treat hydrogen sulfide (H2S) gas generated from a primary sludge settling unit process. The OHS team included an industrial hygiene/environmental health engineering specialist, an occupational safety specialist, an occupational health physician, and an occupational health nurse. Concerns were raised regarding the possibility of adverse health effects to maintenance workers during "conditioning" of the biofilter compost-like media beds. Conditioning activities may include in-situ rearrangement of the existing media, removal from the tank/surface, drying/reinsertion of the existing media, or complete removal of the media, and replacement with new. Neither the design engineering firm nor the manufacturer had specific written recommendations or precautions regarding exposure during the conditioning of the compost beds. No personal protection equipment has been used for this activity. The expected agents for adverse health effects associated with this unit process are respirable particulate dust and bioaerosols, which may contain viable bacteria and fungi, as well as endotoxin. Safety procedures are already in place for H2S. Mixed dust from the compost media bed may cause irritation of pre-existing health conditions such as asthma, chronic lung disease, and some skin conditions, and may also lead to new health problems such as inhalation fever, occupational asthma, hypersensitivity pneumonitis, skin rashes and/or skin infections, and upper or lower respiratory infections. Air samples were taken immediately before (background samples) and during a simulation of the conditioning procedure of one of the two compost beds. Airborne samples collected during the simulated procedure yielded more bacteria per volume of collected air than the background samples. These findings suggest an increased risk for bacterial infection during the conditioning procedure. The airborne samples cultured for fungi during the simulation were less than the background sample. Stachybotrys chartarum was not detected in a sample of the filter media. As with the fungi data, endotoxin air sampling yielded less endotoxin during the simulated conditioning procedure than in the background. Two inches of rain had fallen in the 24 hours preceding the sampling, soaking the upper layers of the compost media. Sampling during an actual conditioning procedure on a warm, dry day may yield additional evidence relevant to potential health risks from dust and microorganisms. Although the data is not representative of an actual conditioning procedure, the following common sense precautions are recommended: (1) Dust minimization during dry conditions can be achieved by thoroughly wetting the compost bed prior to removing the compost, and wetting the compost again before returning it to the bed. (2) Based on scientific literature rather than this project's sampling results, the use of an appropriate respirator should be proactively considered. In addition, consideration must be given to the worker's cardiopulmonary effects associated with respirator use, decreased work performance effects, and OSHA administrative requirements of a respirator protection program. (3) Workers with immunocompromised status, asthma, allergic rhinitis/conjunctivitis, or allergic conditions of the skin, eyes, or lungs should be excluded from this particular job, unless it can be shown that their personal protective equipment is effective. (4) Protective outer wear, goggles, and gloves should be worn to minimize health risks associated with clothing garments contaminated by microorganisms.

Aerosols↗

Neutrophil precursor generation: effects of culture conditions.

The influence of feeding schedules on the expansion and differentiation of enriched PB CD34+ cells (84.9+/-14.7% purity) was studied after 12-13 days of serum-free liquid culture. CD34+ cell cultures were initiated (n=6) on day 0 (2 x 10(5) cells) in X-VIVO 10 medium containing 1% human albumin (HA) and 100 ng/ml each of rIL-3, rIL-6, rSCF, and rG-CSF. The cultures were supplemented on days 3, 6, and 9 as follows: condition 1, unfed (static culture); condition 2, 100 ng/ml rG-CSF; condition 3, split 1:2 medium + 100 ng/ml each rIL-3, rIL-6, rSCF, and rG-CSF; condition 4, split 1:2 medium + 100 ng/ml rG-CSF. The proliferative capacities (fold increase) of condition 2 (49.1+/-21.3), condition 3 (75.6+/-33.4), and condition 4 (63.1+/-23.8) cultures were significantly higher (p < 0.05) than that of the condition 1 unfed (35.5+/-14.0) cultures. Flow cytometric analysis (CD15-FITC/CD11b-PE) showed that the highest CD15+ cell purity (neutrophil precursors) was found in the condition 3 (1.18 x 10(7)+/-4.29 x 10(6)) cultures, followed by condition 4 (9.84 x 10(6)+/-3.57 x 10(6)), condition 2 (7.54 x 10(6)+/-2.06 x 10(6)), and condition 1 (4.78 x 10(6)+/-9.80 x 10(5)), respectively. The average cloning efficiency of the day 0 enriched CD34+ cells, 15.1%+/-10.3%, decreased to less than 0.2% in all of the day 12-13 cultures. These data suggest that feeding CD34+ cell cultures with rG-CSF alone, medium + rG-CSF, or medium + rIL3, rIL-6, rSCF, and rG-CSF enhances CD15+ neutrophil precursor (promyelocytes, myelocytes, metamyelocytes) production in vitro.

Antigens, CD34↗

Limiting comorbid conditions and breast cancer stage at diagnosis.

BACKGROUND: Contrasting hypotheses exist regarding the relationship between comorbidity and breast cancer stage at diagnosis. One suggestion is that disabling comorbid conditions would result in a later stage diagnosis of breast cancer because such conditions would limit mobility and thus access to medical care. This article examines this hypothesis by building a comorbidity summary measure of functionally limiting comorbid conditions and by testing the effectiveness of this measure in predicting the stage at which breast cancer is diagnosed. METHODS: Cases with newly diagnosed breast cancer were identified through the population-based Metropolitan Detroit Cancer Surveillance System, a participant of the Surveillance, Epidemiology, and End Results Program of the National Cancer Institute. Of 1191 eligible cases, 1011 (85%) were interviewed 2-4 months following diagnosis. The analyses for this study were limited to 731 cases for which there were complete data on all variables. Five individual comorbid conditions that predicted functional limitation were combined into a comorbidity summary measure: arthritis, eye conditions, gastrointestinal conditions, kidney conditions, and respiratory conditions. Breast cancer stage was categorized in relation to whether women had local or advanced (regional or remote) disease. RESULTS: Women with two or more of these five functionally limiting conditions were about half as likely as those with none of these conditions to receive an advanced stage diagnosis of breast cancer (odds ratio [OR] = 0.49, 95% confidence interval [CI] 0.28-0.86, p = .01). CONCLUSIONS: These findings do not support the suggestion that the presence of disabling comorbid conditions results in later stage breast cancer. The five conditions summarized by this measure, although functionally limiting, may also require greater medical monitoring due to associated symptoms and/or treatment requirements and thus lead to increased opportunities for cancer screening.

Adult↗

Level of sleepiness and total sleep time following various time in bed conditions.

The effects of various time in bed (TIB) conditions on daytime sleepiness and total sleep time (during a 24-hour enforced bedtime) were investigated. Thirty-two healthy male subjects participated in the study. Subjects were assigned to one of four groups to balance average screening multiple sleep latency tests (MSLT). Subjects were randomly assigned to spend 8, 6, 4 or 0 hours time in bed. They underwent the same TIB condition twice with at least 7 days between the two sessions. Following their assigned time in bed conditions, subjects were counterbalanced to have a standard MSLT and a 24-hour enforced bedtime protocol. To assess the effect of TIB on the MSLT, the sleep latencies were submitted to a four (TIB condition) by four (nap test) multivariate analysis of variance. The sleep latencies were shorter for those subjects in the 0-hours condition when compared to the other three conditions. Also, the sleep latencies of those subjects in the 4- and 6-hour conditions were comparable but different from those of subjects in the 8- and 0-hour TIB conditions. To assess the effect of TIB on the 24-hour enforced bedtime, the total sleep time during this period was submitted to a six (4-hour block) by four (TIB condition) multivariate analysis of variance. Subjects slept more following 0 hours TIB when compared to the other three conditions. There were no statistically significant differences between the 8-, 6- and 4-hour TIB conditions. Across conditions, subjects slept more during the first 4 hours when compared to blocks 2, 3, 4 and 5. Blocks 1 and 6 were comparable.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Physiological studies of chloramine resistance developed by Klebsiella pneumoniae under low-nutrient growth conditions.

This study investigated the physiological mechanisms of resistance to chloramines developed by Klebsiella pneumoniae grown in a nutrient-limited environment. Growth under these conditions resulted in cells that were smaller than cells grown under high-nutrient conditions and extensively aggregated. Cellular aggregates ranged from 10 to more than 10,000 cells per aggregate, with a mean population aggregate size of 90 cells. This aggregation may have been facilitated by the presence of extracellular polymer material. By using glucose as a reference of capsule content, it was determined that growth under low-nutrient conditions produced cells with 8 x 10(-14) to 41 x 10(-14) g of carbohydrate per cell, with a mean +/- standard deviation of 27 x 10(-14) +/- 16 x 10(-14) g of carbohydrate per cell. In comparison, growth under high-nutrient conditions resulted in 2.7 x 10(-14) to 5.9 x 10(-14) g of carbohydrate per cell, with a mean and standard deviation of 4.3 x 10(-14) +/- 1.2 x 10(-14) g of carbohydrate per cell. Cell wall and cell membrane lipids also varied with growth conditions. The ratio of saturated to unsaturated fatty acids in cells grown under low-nutrient conditions was approximately five times greater than that in cells grown under high-nutrient conditions, suggesting possible differences in membrane permeability. An analysis of sulfhydryl (-SH) groups revealed no quantitative difference with respect to growth conditions. However, upon exposure to chloramines, only 33% of the -SH groups of cells grown under low-nutrient conditions were oxidized, compared with 80% oxidization of -SH groups in cells grown under high-nutrient conditions. The reduced effectiveness of chloramine oxidization of -SH groups in cells grown under low-nutrient conditions may be due to restricted penetration of chloramines into the cells, conformational changes of enzymes, or a combination of both factors. The results of this study suggest that chloramine resistance developed under low-nutrient growth conditions may be a function of multiple physiological factors, including cellular aggregation and protection of sulfhydryl groups within the cell.

Bacterial Adhesion↗

Equity and medical practice variation: relationships between standardised discharge ratios in total and for selected conditions in English districts.

STUDY OBJECTIVE: The aim was to investigate relationships for residents of English district health authorities between rates of discharges from acute hospitals for all conditions and variations in discharge rates for eight common conditions (five surgical, three medical). DESIGN: Hospital Inpatient Enquiry data on discharges for 1984 were analysed. Standardised discharge ratios (ratios of actual to expected numbers of discharges x 100) were derived for selected conditions and all conditions; and correlation coefficients for these statistics were calculated. Districts were grouped into quintiles according to the value of the standardised discharge ratio, and systematic variation within each quintile was calculated for the selected conditions. SETTING: The study involved all 192 English district health authorities, but 57 were excluded because the proportion of unspecified diagnoses exceeded 5%. PATIENTS: The analyses were based on 336,799 cases from 135 districts. MEASUREMENTS AND MAIN RESULTS: Discharge ratios for the medical conditions and one surgical condition were significantly correlated with the levels of total discharge rates (p less than 0.01). The medical conditions showed greater systematic variation in discharge ratios than the surgical conditions. There was no consistent pattern in the values of systematic variation for the selected conditions across the different levels of discharge ratios for all conditions. CONCLUSIONS: It is argued that the changes in the NHS introduced in April 1991 are intended to introduce greater equity in the standardised discharge ratios and increase the total numbers of discharges. The results of this analysis suggest that, even if these objectives were achieved, they may not result in increased levels of elective care, nor result in greater equity in terms of rates of discharge for individual conditions.

Acute Disease↗

Acute effects of thixotropy conditioning of inspiratory muscles on end-expiratory chest wall and lung volumes in normal humans.

Thixotropy conditioning of inspiratory muscles consisting of maximal inspiratory effort performed at an inflated lung volume is followed by an increase in end-expiratory position of the rib cage in normal human subjects. When performed at a deflated lung volume, conditioning is followed by a reduction in end-expiratory position. The present study was performed to determine whether changes in end-expiratory chest wall and lung volumes occur after thixotropy conditioning. We first examined the acute effects of conditioning on chest wall volume during subsequent five-breath cycles using respiratory inductive plethysmography (n = 8). End-expiratory chest wall volume increased after conditioning at an inflated lung volume (P < 0.05), which was attained mainly by rib cage movements. Conditioning at a deflated lung volume was followed by reductions in end-expiratory chest wall volume, which was explained by rib cage and abdominal volume changes (P < 0.05). End-expiratory esophageal pressure decreased and increased after conditioning at inflated and deflated lung volumes, respectively (n = 3). These changes in end-expiratory volumes and esophageal pressure were greatest for the first breath after conditioning. We also found that an increase in spirometrically determined inspiratory capacity (n = 13) was maintained for 3 min after conditioning at a deflated lung volume, and a decrease for 1 min after conditioning at an inflated lung volume. Helium-dilution end-expiratory lung volume increased and decreased after conditioning at inflated and deflated lung volumes, respectively (both P < 0.05; n = 11). These results suggest that thixotropy conditioning changes end-expiratory volume of the chest wall and lung in normal human subjects.

Adult↗

Self-reported chronic conditions and EQ-5D index scores in the US adult population.

OBJECTIVE: To examine the unique health-related quality of life (HRQoL) decrements associated with common chronic conditions in the general US adult population. METHODS: Data were obtained from a study aimed at establishing a US population-based set of preference weights for the health states defined by the EQ-5D. The EQ-5D is a brief, self-completed instrument for describing and valuing HRQoL. As part of that study, along with the EQ-5D items, data regarding socio-demographic characteristics and chronic medical conditions were collected. The EQ-5D has five dimensions, from which an index score can be calculated that falls on a scale where 0.0 = death and 1.0 = perfect health. Ordinary least squares regression models were conducted using the EQ-5D index score as the dependent variable to estimate the association between each chronic condition and the index score after adjusting for socio-demographic variables. The population sampling weights were applied in the analyses to adjust for the over-sampling of the minority groups. RESULTS: Approximately three-fifths (62.5%) of the study sample reported having at least one of the 18 chronic medical conditions; sinusitis(24.8%), hypertension (23.5%), and arthritis (21.5%) were the most commonly reported conditions. The chronic conditions that had the greatest negative association with EQ-5D index scores were depression and arthritis. CONCLUSION: Unique associations were found between several chronic conditions and HRQoL after accounting for the presence of other conditions and socio-demographic characteristics. The results of this study provide an indication of the relative HRQoL decrements associated with various chronic conditions in the general US adult population. The major limitation of this analysis is the uncertainty of the causal relationship between chronic conditions and HRQoL due to the cross-sectional nature of the study data. In addition, because it was unknown how well the conditions were managed, caution is needed in interpreting study results regarding the relative impact of chronic conditions on HRQoL.

Adult↗

Deductive reasoning from uncertain conditionals.

This paper begins with a review of the literature on plausible reasoning with deductive arguments containing a conditional premise. There is concurring evidence that people presented with valid conditional arguments such as Modus Ponens and Modus Tollens generally do not endorse the conclusion, but rather find it uncertain, in case (1) the plausibility of the major conditional premise is debatable, (2) the major conditional premise is formulated in frequentist or probabilistic terms, or (3) an additional premise introduces uncertainty about the major conditional premise. This third situation gives rise to non-monotonic effects by a mechanism that can be characterized as follows: the reasoner is invited to doubt the major conditional premise by doubting the satisfaction of a tacit condition, which is necessary for the consequent to occur. Three experiments are presented. The first two aim to generalize the latter result using various types of conditionals and the last shows that performance in conditional reasoning is significantly affected by the representation of the task. This third point is discussed along with various other issues: we propose a pragmatic account of how the tacit conditions mentioned earlier are treated in plausible reasoning; the relationship of this account with the conditional probability view on conditional sentences is examined; an application of the same account to the Suppression Effect (Byrne, 1989) is proposed and compared with the counter-example availability explanation; and finally, some suggestions on how uncertainty could be implemented in a mental logic system are presented.

Adolescent↗

Body condition scores of Holstein cows on Prince Edward Island, Canada: relationships with yield, reproductive performance, and disease.

An observational study of 429 Holstein cows in 13 herds (mean 305-FCM yield of 7225 kg) was conducted to determine the relationship between body condition score and its changes with milk yield, reproductive performance, and disease incidence. Cows were scored once for body condition during the dry period, near calving, and then every 14 d until termination of lactation. Condition score at calving had no effect on either peak of 305-d milk yields. Condition loss averaged .73 and .83 points for primiparous and multiparous cows, respectively. The duration and magnitude of condition loss depended primarily on score at calving and was greater for cows that calved with higher condition scores. After reaching minimum score, cows gained an average of .53 condition points in the remainder of lactation. Total amount of gain was not affected by body condition score at calving or by milk yield. No significant differences were found for days to first observed estrus, days to first breeding, days to conception, or number of times bred for cows grouped by body condition score at calving or by condition loss between calving and first breeding. Body condition score at calving was not significantly different for diseased cows. Cows that were diagnosed with a disease lost more condition than undiseased cows, but the difference generally was < .25 points.

Animal Nutritional Physiological Phenomena↗

Retrospective survey of long-term care staff: 12 conditions identified, evaluated, and reported as suspected adverse drug reactions.

OBJECTIVE: To examine the identification of conditions, the evaluation of these conditions as adverse drug reactions (ADRs), and the communication practices regarding suspected ADRs in a long-term care (LTC) facility. DESIGN AND SETTING: Health care providers completed a survey containing nine questions covering 13 conditions, about residents of a 99-bed LTC facility. PARTICIPANTS: Twenty-five health care providers (i.e., CNAs, LPNs, RNs, RPh, social workers, and an activities worker) reviewed residents on their units. A total of 67 residents were reviewed. RESULTS: The RPh was aware of fewer of the residents' conditions (16% of all conditions) compared with CNAs (34%), LPNs (38%), and RNs (45%). RNs and the RPh identified an equal percent of conditions that could be caused by a resident's medications (66.5% and 66.7% of all conditions, respectively). This was greater than LPNs (36%) or CNAs (9.9%). However, RNs and the RPh actually attributed a lower percentage of these conditions to the medications (43.9% and 41.7%, respectively) compared with LPNs (57.4%) and CNAs (90.0%). CNAs notified others in a higher percentage of the cases where they suspected an ADR (81.5%) compared with the RPh (60%), RNs (57.4%), or LPNs (10.3%). No notification was primarily attributed to "nothing could be done," the condition is an expected effect, others were aware of the condition, and the condition currently is being treated. CONCLUSIONS: These results illustrate the importance of a team approach to ensure that all health care providers are aware of conditions to properly evaluate and resolve them.

Journal Article↗

Conditioned medium increases the rate of neurite elongation: separation of this activity from the substratum-bound inducer of neurite outgrowth.

Heart cell-conditioned medium supports extensive neurite outgrowth from dissociated parasympathetic neurons of the chicken embryo ciliary ganglion. We have shown previously that neurite outgrowth in this system depends on the deposition of a substratum-conditioning factor from conditioned medium onto the polyornithine culture substratum. However, in the presence of only the substratum-bound material, neurite outgrowth is never as extensive as in whole conditioned medium. The present report demonstrates that a different and soluble component of conditioned medium is required to achieve the rates of neurite elongation normally observed in whole conditioned medium. This second component, while unable by itself to support neurite outgrowth, is able to increase the rate of neurite elongation approximately 3-fold within 30 to 60 min of its addition. This conclusion is based on direct time-lapse observations of the rate of elongation of individual neurites before and after the addition of fractions of conditioned medium previously depleted of the substratum-conditioning factor. Correlated with the effect of such fractions of conditioned medium on the rate of neurite elongation is a change in the morphology of the growth cones, which become larger and more spread. The activity of the soluble, elongation-promoting component of conditioned medium is nondialyzable and is sensitive to treatments known to affect proteins, such as repeated freeze-thawing, heating, and trypsinization. Fractions of conditioned medium which contain the elongation-promoting activity also contain all of the survival factor for parasympathetic neurons previously shown to be present in heart cell-conditioned medium. The methods described here represent a convenient new assay which we have used recently to demonstrate elongation-promoting factors with neuronal specificity in extracts of rat hippocampus.

Animals↗

Awareness predicts the magnitude of single-cue trace eyeblink conditioning.

Studies of differential eyeblink conditioning (CS+ and CS-) have demonstrated that successful conditioning requires awareness of the stimulus contingencies and that delay conditioning does not. Two experiments were carried out to determine whether awareness is also important for single-cue trace eyeblink conditioning. In experiment 1, participants who performed a secondary, attention-demanding task emitted significantly fewer conditioned eyeblink responses than participants who watched a silent movie during the conditioning session. In experiment 2, participants who became aware of the stimulus contingencies early in the conditioning session emitted significantly more conditioned responses during the remainder of the session than participants who became aware later in the session or who never became aware. These results indicate that awareness is important for single-cue trace eyeblink conditioning, just as it is for differential trace conditioning. The relationship between awareness and trace eyeblink conditioning is discussed in the light of these and other recent findings.

Aged↗

The Pavlovian analysis of instrumental conditioning.

An account was given of the development within the Russian literature of a uniprocess formulation of classical and instrumental conditioning, known as the bidirectional conditioning hypothesis. The hypothesis purports to offer a single set of Pavlovian principles to account for both paradigms, based upon a neural model which assumes that bidirectional (forward and backward) connections are formed in both calssical and instrumental conditioning situations. In instrumental conditioning, the bidirectional connections are hypothesized to be simply more complex than those in classical conditioning, and any differences in empirical functions are presumed to lie not in difference in mechanism, but in the strength of the forward and backward connections. Although bidirectional connections are assumed to develop in instrumental conditioning, the experimental investigation of the bidirectional conditioning hypothesis has been essentially restricted to the classical conditioning operations of pairing two CSs (sensory preconditioning training), a US followed by a CS (backward conditioning training) and two USs. However, the paradigm involving the pairing of two USs, because of theoretical and analytical considerations, is the one most commonly employed by Russian investigators. The results of an initial experiment involving the pairing of two USs, and reference to the results of a more extensive investigation, leads us to tentatively question the validity of the bidirectional conditioning account of instrumental conditioning.

Animals↗

beta2 subunit-containing nicotinic receptors mediate the enhancing effect of nicotine on trace cued fear conditioning in C57BL/6 mice.

RATIONALE: Previous research indicates that acute nicotine administration enhances the acquisition of contextual fear conditioning and trace cued fear conditioning. Pharmacological inhibition of alpha4beta2 nicotinic acetylcholine receptors (nAChRs), but not alpha7 nAChRs, blocked the enhancing effect of nicotine on contextual fear conditioning. Similarly, genetic deletion of the beta2 nAChR subunit but not the alpha7 nAChR subunit blocked the enhancing effect of nicotine on contextual fear conditioning. OBJECTIVES: In the present study, nAChR subunit knockout mice were used to compare the involvement of beta2 subunit-containing nAChRs and alpha7 subunit-containing nAChRs in the effects of nicotine on hippocampus-dependent trace cued fear conditioning and contextual fear conditioning. METHODS: beta2 nAChR subunit knockout mice, alpha7 nAChR subunit knockout mice, and their wild-type littermates received either nicotine or saline 5 minutes before training and testing. Mice were trained using five conditioned stimulus (CS; 30 s, 85 dB white noise)--trace (30 s)--unconditioned stimulus (US; 2 s footshock) pairings. Freezing to the context and freezing to the CS were assessed 24 h later. RESULTS: Both contextual and trace cued fear conditioning were enhanced by nicotine administration in wild-type littermates and in alpha7 nAChR subunit knockout mice. In contrast, neither contextual fear conditioning nor trace cued fear conditioning was enhanced by nicotine administration in beta2 nAChR subunit knockout mice. CONCLUSIONS: These results suggest that beta2 subunit-containing nAChRs but not alpha7 nAChR subunit-containing nAChRs are critically involved in the enhancing effect of nicotine on contextual and trace cued fear conditioning.

Acoustic Stimulation↗

Classical conditioning of the eyeblink reflex in the decerebrate-decerebellate rabbit.

The purpose of these experiments was to test the hypothesis that a conditioned nictitating membrane reflex can be acquired in decerebrate rabbits in the absence of the cerebellum. Experiments examining the effects of large cerebellar lesions on the acquisition and performance of the conditioned reflex were performed in acutely prepared decerebrate rabbits. Most lesions encompassed all of the cerebellar nuclear regions ipsilateral to the eye receiving the unconditioned stimulus. In all rabbits included in this study the continuity between the cerebellar nuclei and the brainstem was interrupted, even in those preparations in which small regions of the nuclei were present in the lateral hemisphere. The findings demonstrate that these animals could acquire the conditioned reflex independent of whether conditioning had occurred prior to the cerebellectomy. Strong associativity was found between the latency of the conditioned response and the interstimulus interval between the conditioned and unconditioned stimuli. The behavior of the conditioned reflex observed in the decerebrate-decerebellate animals differed from that reported for awake intact rabbits in two ways. Once the conditioned behavior had been acquired, the percent of trials showing conditioned responses was somewhat less in decerebrate-decerebellate rabbits and was also more variable in these animals. The data demonstrate that the nictitating membrane reflex can be classically conditioned in the absence of the cerebellum, indicating that this structure is neither necessary nor sufficient for the acquisition of this type of conditioned behavior. In addition, an hypothesis is presented which addresses the difference between the data reported here and those previously reported by other laboratories based on observations in awake intact animals.

Animals↗

Role of hippocampal NMDA receptors in trace eyeblink conditioning.

We examined the effects of acute injections of competitive N-methyl-D-aspartate (NMDA) receptor antagonist 2-amino-5-phosphonovaleric acid (APV) into the dorsal hippocampus on contextual fear conditioning and classical eyeblink conditioning in C57BL/6 mice. When injected 10 to 40 min before training, APV severely impaired contextual fear conditioning. Thus, APV injection under these conditions was sufficient to suppress hippocampal NMDA receptors. To investigate the role of hippocampal NMDA receptors on eyeblink conditioning, we carried out daily training of mice during 10-40 min after injection of APV. In the delay eyeblink conditioning, in which the unconditioned stimulus (US) is delayed and terminates simultaneously with the conditioned stimulus (CS), APV-injected mice acquired the conditioned responses (CRs) as well as artificial cerebrospinal fluid (aCSF)-injected control mice did. However, in the trace eyeblink conditioning, in which the CS and US were separated by a stimulus-free trace interval of 500 ms, APV-injected mice showed severe impairment in acquisition of the CR. There was no significant difference in pseudo-conditioning between APV- and aCSF-injected mice. These results provide evidence that the NMDA receptor in the dorsal hippocampus is critically involved in acquisition of the CR in long trace eyeblink conditioning.

2-Amino-5-phosphonovalerate↗

Discharge profiles of abducens, accessory abducens, and orbicularis oculi motoneurons during reflex and conditioned blinks in alert cats.

The discharge profiles of identified abducens, accessory abducens, and orbicularis oculi motoneurons have been recorded extra- and intracellularly in alert behaving cats during spontaneous, reflexively evoked, and classically conditioned eyelid responses. The movement of the upper lid and the electromyographic activity of the orbicularis oculi muscle also were recorded. Animals were conditioned by short, weak air puffs or 350-ms tones as conditioned stimuli (CS) and long, strong air puffs as unconditioned stimulus (US) using both trace and delayed conditioning paradigms. Motoneurons were identified by antidromic activation from their respective cranial nerves. Orbicularis oculi and accessory abducens motoneurons fired an early, double burst of action potentials (at 4-6 and 10-16 ms) in response to air puffs or to the electrical stimulation of the supraorbital nerve. Orbicularis oculi, but not accessory abducens, motoneurons fired in response to flash and tone presentations. Only 10-15% of recorded abducens motoneurons fired a late, weak burst after air puff, supraorbital nerve, and flash stimulations. Spontaneous fasciculations of the orbicularis oculi muscle and the activity of single orbicularis oculi motoneurons that generated them also were recorded. The activation of orbicularis oculi motoneurons during the acquisition of classically conditioned eyelid responses happened in a gradual, sequential manner. Initially, some putative excitatory synaptic potentials were observed in the time window corresponding to the CS-US interval; by the second to the fourth conditioning session, some isolated action potentials appeared that increased in number until some small movements were noticed in eyelid position traces. No accessory abducens motoneuron fired and no abducens motoneuron modified their discharge rate for conditioned eyelid responses. The firing of orbicularis oculi motoneurons was related linearly to lid velocity during reflex blinks but to lid position during conditioned responses, a fact indicating the different neural origin and coding of both types of motor commands. The power spectra of both reflex and conditioned lid responses showed a dominant peak at approximately 20 Hz. The wavy appearance of both reflex and conditioned eyelid responses was clearly the result of the high phasic activity of orbicularis oculi motor units. Orbicularis oculi motoneuron membrane potentials oscillated at approximately 20 Hz after supraorbital nerve stimulation and during other reflex and conditioned eyelid movements. The oscillation seemed to be the result of both intrinsic (spike afterhyperpolarization lasting approximately 50 ms, and late depolarizations) and extrinsic properties of the motoneuronal pool and of the circuits involved in eye blinks.

Abducens Nerve↗