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Biomedical subjects

R W Winters

Publications and source records attributed to R W Winters.

At least 19 recordsLinked to original sources
PubMed2000

Afferents to the central nucleus of the amygdala and functional subdivisions of the periaqueductal gray: neuroanatomical substrates for affective behavior.

Evidence suggests the periaqueductal gray (PAG) is involved in the integration of behavioral and autonomic components of affective behavior. Our laboratory has shown that electrical stimulation of the ventrolateral periaqueductal gray (vl PAG) versus the dorsolateral periaqueductal gray (dl PAG), in the rabbit, elicits two distinct behavioral/cardiorespiratory response patterns. Furthermore, evidence suggests that the amygdaloid central nucleus (ACe) may influence cardiovascular activity during emotional states. The purpose of this study was to delineate the topography and determine the origin of forebrain projections to the PAG and the ACe, as well as commonalties and differences in the pattern of afferents. Examination of common afferents may lend insights into their function as components of a forebrain system regulating autonomic activity during emotional states. Separate retrograde tracers were injected into functional subdivisions of the PAG and the ACe in rabbits. PAG injections led to neuronal labeling in numerous cortical regions including the ipsilateral medial prefrontal and insular cortices. Additionally, bilateral labeling was observed in several hypothalamic nuclei including the paraventricular nucleus, the dorsomedial nucleus and the ventromedial nucleus as well as the region lateral to the descending column of the fornix. Sparse labeling was also seen in various basal forebrain regions, thalamic nuclei and amygdaloid nuclei. Many of these regions were also labeled following injections in the ACe. Although double-labeled cells were never observed, afferents to the ACe were often proximal to PAG afferents. Implications of these findings are discussed in terms of two functionally distinct behavioral/cardiovascular response patterns.

Affective Symptoms↗
PubMed1999

Contribution of NMDA and non-NMDA receptors to synaptic transmission from the brachium of the inferior colliculus to the medial subdivision of the medial geniculate nucleus in the rabbit.

Previous work from this laboratory has demonstrated that monosynaptic inputs from the brachium of the inferior colliculus (BIC) to the medial subdivision of the medial geniculate nucleus (mMG) strengthen as a result of associative conditioning with an acoustic conditioned stimulus (i.e., fear conditioning). One model that has been proposed to underlie certain types of neuronal plasticity involves the recruitment of N-methyl-D-aspartic acid (NMDA)-type glutamate receptors. The purpose of the present study was to examine the relative contributions of glutamatergic NMDA and non-NMDA receptors to synaptic transmission within this pathway. Individual contributions of the specific receptor types were assessed through the use of 2-amino-5-phosphonovaleric acid (AP5), a selective NMDA receptor antagonist, and 6-cyano-5-nitroquinoxaline-2,3-dione (CNQX), a non-NMDA receptor antagonist. Bipolar stimulating electrodes were stereotaxically implanted in BIC and recording electrodes (attached to dual 32-gauge cannulae for delivery of drug) were positioned in mMG of New Zealand albino rabbits. Single pulses (150 micros, 100-350 microA) delivered to BIC resulted in short-latency (<4 ms) responses in mMG. BIC-evoked single-unit activity was recorded from mMG before, during, and at several intervals after injection of AP5, CNQX, and/or artificial cerebrospinal fluid (ACSF). Injection of either AP5 or CNQX, but not ACSF, significantly attenuated the short-latency BIC-evoked responses in the vast majority of cells tested. These findings suggest that the monosynaptic pathway from BIC to mMG is glutamatergic and that this pathway frequently employs NMDA-type receptors during electrically stimulated synaptic transmission. Due to the NMDA receptors' proposed role in plasticity (e.g., long-term potentiation), these results may have implications for understanding the mechanisms of synaptic plasticity observed at this synapse during associative learning.

2-Amino-5-phosphonovalerate↗
PubMed1996

Changes of synaptic efficacy in the medial geniculate nucleus as a result of auditory classical conditioning.

In this study we examined inputs to neurons in the medial subnucleus of the medial geniculate nucleus (mMG) for changes of synaptic efficacy associated with heart-rate conditioning to an auditory conditioned stimulus (CS). Conditioning-related changes of synaptic efficacy were measured in awake animals by examining mMG single-unit responses evoked by stimulation of one of two areas that send auditory CS and nonauditory information monosynaptically to the mMG, the brachium of the inferior colliculus (BlC) and the superior colliculus (SC). Synaptic efficacy was measured before, immediately after, and 1 hr after one session of classical conditioning with a tone CS and a corneal airpuff unconditioned stimulus. To determine whether conditioning produced changes of synaptic efficacy on the auditory BlC inputs to mMG cells and not general changes of cellular excitability, analyses of synaptic efficacy were performed on the mMG units that exhibited short-latency evoked responses (< 3.5 msec) to both BlC and SC stimulation. Analyses revealed that the BlC but not the SC test stimulus-evoked unit activity from the same neurons exhibited the following changes immediately after conditioning: decreases in unit response latency, increases in unit response reliability, and increases in spike frequency. BlC-evoked unit responses after pseudoconditioning did not exhibit these changes in unit responding. These results suggest that the synapses carrying auditory CS information to mMG neurons increase in strength as the result of associative conditioning with an acoustic CS. Some of these changes of synaptic efficacy remained 1 hr after training.

Acoustic Stimulation↗
PubMed1996

Modulation of the baroreceptor reflex by stimulation of the hypothalamic defense and vigilance areas.

Electrical stimulation of the hypothalamic defense area (HDA) elicits a pressor/tachycardia response that is believed to prepare an animal for fight or flight. In contrast, electrical stimulation of the hypothalamic vigilance area (HVA) evokes a pressor/bradycardia response that is associated with the inhibition of movement. The differences in the behavioral components of these two affective response patterns suggest differential modulation of the baroreceptor reflex. The present study tested this idea by assessing the effects of electrical stimulation of the HDA and the HVA upon the bradycardia/depressor response elicited by stimulation of the aortic nerve (AN) in rabbits. Concurrent HDA and AN stimulation was observed to attenuate the AN-elicited bradycardia but enhanced the depressor response elicited by AN stimulation. In contrast, concurrent stimulation of the HVA and AN enhanced the bradycardia elicited by AN stimulation but reduced the magnitude of the AN-elicited depressor response. These results provide evidence for differential modulation of the baroreceptor reflex during the defense and vigilance reactions.

Aggression↗
PubMed1994

Basal and reactive plasma catecholamine levels under stress and anesthesia in rabbits.

The present study was undertaken to determine if electrical stimulation of the hypothalamic defense area (HDA) and baroreflex activation elicited by head up body tilt produced changes in plasma catecholamine (CA) levels in anesthetized rabbits. We also compared the effects of two anesthetics, isoflurane and sodium pentobarbital, upon basal and reactive CA levels, and upon autonomic reactivity. HDA stimulation was found to produce significant increases in plasma norepinephrine (NE) levels but not epinephrine (E) levels. Passive tilt was found to produce statistically significant increases in NE levels for both anesthetics used and a significant increase in E levels for animals anesthetized with isoflurane. Basal and reactive measurements provided evidence that pentobarbital has a more suppressive effect upon the autonomic nervous system than isoflurane: (a) Basal NE levels were significantly lower in pentobarbital anesthetized animals than in isoflurane-anesthetized animals; and (b) Baroreceptor sensitivity to a passive tilt stressor was significantly higher for animals anesthetized with isoflurane than for animals anesthetized with pentobarbital.

Anesthesia, General↗
PubMed1994

Comparison of peripheral blood flow patterns associated with the defense reaction and the vigilance reaction in rabbits.

The present study compared the skeletal muscle and visceral blood flow patterns elicited by electrical stimulation of the hypothalamic defense area (HDA) and the hypothalamic vigilance area (HVA) of the rabbit. Electrical stimulation of the HDA evoked a pressor response, tachycardia, hyperventilation, an increase in blood flow to the skeletal muscles and decreased blood flow to visceral organs. Stimulation of the HVA yielded a pressor response, bradycardia, inspiratory apnea and decreased blood flow to both the skeletal muscles and the viscera. Intravenous injections of atropine methyl nitrate significantly reduced the HVA-elicited bradycardia and the HDA-elicited increase in blood flow to the skeletal muscles, thereby providing evidence that the bradycardia was mediated by vagal efferents and that the rabbit has an atropine-sensitive cholinergic vasodilation system. The decrease of blood flow to the visceral organs associated with the defense reaction and vigilance reaction was reversed by intravenous injections of the alpha-1 receptor blocker prazosin.

Animals↗
PubMed1994

The service-intensive nature of home infusion therapy: Part II.

The author presents a detailed, two-part discussion of the types and intensity of various services that are essential to the provision of home infusion therapy. In doing so, it is hoped that the reader obtains a better understanding of the critical role that these services play in the provision of home infusion therapies.

Community Health Nursing↗
PubMed1994

Home infusion therapy meets managed care: confrontation or cooperation.

The relatively uncommon experience of patients using home infusion therapy but at relatively great expense has led to problems, sometimes confrontational, between managed care organizations and home infusion therapy providers. The principal barriers to smooth contracting relationships are described by the author, who also proposes ways to create a win-win environment.

Capitation Fee↗
PubMed1991

Electrophysiological evidence for hypothalamic defense area input to cells in the lateral tegmental field of the medulla of rabbits.

Single cell recordings were made from neurons in the lateral tegmental field of the medulla (LTFM) during electrical stimulation of the hypothalamic defense area (HDA) of the rabbit. Fifty-four cells were inhibited by HDA stimulation; 23 of these cells received barosensory input. Twenty-two LTFM cells showed an increase in firing rate during HDA stimulation; 10 of these cells received barosensory input. The results of this study provide evidence that the hypothalamic defense area makes functional connections with cardiovascular-influenced neurons in the LTFM.

Afferent Pathways↗
PubMed1991

Hypothalamic, midbrain and bulbar areas involved in the defense reaction in rabbits.

The present study mapped neuroanatomical sites in the hypothalamus and periaqueductal gray (PAG) of the rabbit which, when stimulated electrically, evoked the cardiorespiratory components of the defense reaction (CRDR). This included increases in heart rate, blood pressure, hindlimb blood flow and respiration rate. All of the components of the CRDR were elicited by electrical stimulation of the posterior hypothalamus, at sites dorsal and medial to the fornix. Although there were regions throughout the PAG in which electrical stimulation elicited concomitant increases in blood pressure, hindlimb blood flow and respiration rate, only stimulation of the dorsal PAG evoked tachycardia. Injection of horseradish peroxidase into the rostral ventrolateral medulla (RVLM) led to heavy retrograde and anterograde labeling in the region of the hypothalamus that yielded the CRDR when stimulated electrically. Heavy labeling was also observed in the dorsal and ventral PAG. The results of this study provide evidence that the posterior hypothalamus and the dorsal PAG are nodal structures in the mediation of the CRDR and that cells in posterior hypothalamus, dorsal PAG and ventral PAG make monosynaptic connections with the RVLM.

Agonistic Behavior↗
PubMed1991

Blood pressure reactivity and perception of pain during the forehead cold pressor test.

The relationship between blood pressure reactivity and the perception of pain was examined during a series of three forehead cold pressor tests given every other day to a group of 18 male college students. Subjects classified as high reactors on the basis of peak increases in mean blood pressure during cold pressor tests perceived the cold pressor stimulus as more painful than subjects classified as low reactors. The propensity to rate the cold pressor stimulus as painful was positively correlated with the individual level of blood pressure reactivity (baseline-free partial r = .62). Intra-individual correlations between pain and blood pressure responses were unrelated to subjects' reactivity status. Across the 3-min test, correlations between pain and blood pressure reactivity (with the effects of baseline blood pressure levels partialled out) were significant only during periods when levels of responses were relatively high. The heart rate responses were unrelated to pain ratings. Generalizability theory was applied to the analysis of temporal stability of cold pressor reactions. Both blood pressure and pain responses were highly reproducible across three sessions, appearing to express stable individual differences. The efficacy of 800 mg oral ibuprofen in controlling the cold pressor pain was also tested. Analgesic activity of the drug during the cold pressor test could not be demonstrated.

Adolescent↗
PubMed1989

Auditory cortex lesions prevent the extinction of Pavlovian differential heart rate conditioning to tonal stimuli in rabbits.

The present study examined the role of the auditory cortex in the extinction of differentially conditioned heart rate (HR) responses in rabbits. Lesions were placed bilaterally in either the auditory cortex or the visual cortex. Three days after recovery from surgery, the auditory cortex lesion group and the visual cortex lesion control group were habituated to the tonal conditioned stimuli (CSs), and then given 2 days of Pavlovian differential conditioning (60 trials per day) in which one tone (CS+) was always paired with the unconditioned stimulus and another tone (CS-) was never paired with the unconditioned stimulus. Animals that had demonstrated reliable differential conditioning (CS+ response at least 5 beats greater than the CS- response) were placed on an extinction schedule for 7 days. The extinction schedule was identical to the differential conditioning schedule with the exception that shock never followed the CS+. The results of the study indicate that auditory cortex lesions prevent the extinction of differential bradycardia conditioned responses (CRs) to tonal CSs. Whereas the bradycardia responses to the CS+ quickly extinguished in the group that had control lesions in the visual cortex, the auditory cortex lesion group continued to exhibit significantly larger bradycardiac HR CRs to the CS+ relative to the CS- during all 7 days of extinction. These results suggest that the animals in the auditory cortex lesioned group did not inhibit responses to a previously reinforced stimulus (i.e., CS+) as well as animals with control lesions in the visual cortex.

Acoustic Stimulation↗
PubMed1988

Cardiovascular responses elicited by electrical and chemical stimulation of the rostral medullary raphe of the rabbit.

Electrical stimulation of the rostral medullary raphe (RMR) of the rabbit elicited pressor responses that were accompanied by tachycardia or bradycardia. Stimulation of dorsal sites (the dorsal raphe obscurus) evoked a pressor/tachycardia response and stimulation of ventral sites (the ventral raphe obscurus, raphe magnus and raphe pallidus) produced a pressor/bradycardia response. Electrical stimulation of the RMR after sinoaortic denervation led to an increase in the magnitude of the pressor response elicited from all stimulation sites, a decrease in the magnitude of the bradycardia produced by stimulation at the ventral sites, but had no effect upon the magnitude of the tachycardia observed from stimulation of the dorsal sites. These findings suggest that electrical stimulation of the dorsal sites leads to inhibition of the cardiomotor component of the baroreceptor reflex. The results of vagal blockade experiments demonstrated that baroreceptor attenuation of the pressor responses at ventral sites was mediated primarily by parasympathetic input to the heart. Chemical stimulation of the RMR with L-glutamate also led to a pressor/tachycardia response at the dorsal sites and a pressor/brachycardia response at the ventral sites. This finding provides evidence that neuronal cell bodies, not axon of passage, mediated the responses elicited by electrical stimulation.

Animals↗
PubMed1988

Anatomical and functional connections of neurons of the rostral medullary raphe of the rabbit.

Single cell recordings were made from neurons in the rostral medullary raphe (RMR) of the rabbit. The recording sites were ones that had been shown to yield pressor responses from electrical stimulation and by pressure injections of glutamate. Electrical stimulation of the intermediolateral (IML) region of the spinal cord led to antidromic activation of 12 of the 100 cells studied. Eleven of these cells were located in raphe pallidus or raphe magnus, and one cell was located in raphe obscurus. These findings were consistent with the results of horseradish peroxidase (HRP) histochemistry experiments. Injections of HRP into the IML led to heavy cell body labeling in raphe pallidus and raphe magnus, but sparse labeling in raphe obscurus. Cells in the RMR could be orthodromically activated by electrical stimulation of the putative defense area of the periaqueductal (PAG) but not by stimulation of putative defense areas in the hypothalamus. Most of these cells were located in raphe pallidus or raphe magnus. Similarly, HRP injections into raphe pallidus and raphe magnus led to heavy cell body labeling in the PAG but not the hypothalamus; no cell body labeling was found in the PAG when injections were made into raphe obscurus.

Action Potentials↗
PubMed1988

Role of auditory cortex in the acquisition of differential heart rate conditioning.

Previous findings from our laboratory indicate that lesions of the auditory cortex disrupt the retention of differentially conditioned bradycardiac responses to tonal stimuli in rabbits. In the present experiment, the effect of lesions of the auditory cortex on the acquisition of differential bradycardiac conditioning was examined. The effect of lesions in the auditory cortex were compared to the effect produced by control lesions in the visual cortex. After 7 days of recovery, animals received 7 days of differential Pavlovian bradycardiac conditioning in which one tone (CS+) was paired with the unconditioned stimulus, and another tone (CS-) was never paired with the unconditioned stimulus. All animals demonstrated differential conditioning during the first 3 days of conditioning. On days 4-7, however, auditory cortex lesioned animals did not exhibit significant differential heart rate (HR) conditioning, whereas control animals with lesions in the visual cortex showed no loss of conditioning during this period. The loss of differential conditioning in animals with lesions in the auditory cortex appears to be due to an increase in the magnitude of the response to the CS-. These data support the hypothesis that the auditory cortex serves to inhibit the response to the CS- in differential conditioning of bradycardia to acoustic stimuli, and that the inhibition may be mediated by a descending corticothalamic or corticolimbic pathway.

Animals↗
PubMed1985

Comparison of signal and adaptive sensitivity profiles of the surround mechanism of cat retinal ganglion cells.

Signal and adaptive sensitivity profiles of the surrounds of cat retinal ganglion cells were determined by varying the position of concentric annuli whose outside and inside diameters varied but whose total area remained constant. Signal sensitivity profiles were determined by adjusting the luminances of these annuli so as to produce a weak suprathreshold response of constant magnitude and time course. Adaptive sensitivity profiles were determined by varying the luminances of concentric equal-area, unmodulated annuli until the response to a temporally modulated annulus attained a criterion level. The results provided evidence that the retinal region over which the surround mechanism of an X cell pools adaptive information and pools signals are the same, and that the distribution of adaptive and signal sensitivities within these regions is similar. A small number of X cells showed local adaptation effects. The adaptive pooling area appeared to be smaller than the signal pooling area for Y cells.

Adaptation, Physiological↗
PubMed1984

History of parenteral nutrition in pediatrics with emphasis on amino acids.

Central venous total parenteral nutrition (TPN) has proved to be a valuable and often life-saving measure in selected newborn infants with surgically repairable, major anomalies of the gastrointestinal tract and infants with chronic intractable diarrhea. However, in infants of low--and especially very low--birth weight, the TPN regimen that was so successful in older infants was frequently associated with severe risks of hyperglycemia. An alternative approach that has proved to be the most satisfactory relies on the fact that the energy expenditure of a premature infant, nursing in a thermally neutral environment, rarely exceeds 50 kcal/kg, a level that can be safely and effectively maintained. With respect to the development of parenteral amino acid solutions, three generations of such mixtures can now be identified. The first of these was represented by the protein hydrolysates. With the advent of technology for the production of pure L-amino acids, a second generation of crystalline mixtures was developed. Evaluation of these revealed that extrapolation from data on oral nutrition was often unsatisfactory for the adequate formulation of such mixtures. The direct study of the parenterally nourished patient led to the third generation of special purpose amino acid solutions such as those targeted for patients with renal failure, liver failure, or trauma or for the promotion of anabolism. It seems likely that development of other solutions will follow the trend of relying on accurate definition of a given metabolic disorder and the perfection of a specific solution to correct it.

Amino Acids↗