David C. Randall

Students are challenged in transitioning from acquiring knowledge and understanding through reading textbooks to their learning to select, read, evaluate, and synthesize the primary literature. A customary approach to teaching this transition to beginning graduate students is for a faculty member to assign "readings" from the recent literature that promise to become key publications; such assignments generally underscore recent, novel scientific content. We advocate here an alternative approach for coaching students very early in their training: first, to read, analyze, and discuss a paper that highlights critically important features of effective and valid experimental design; and, second, to study a paper that can be shown historically to have fundamentally changed the way in which physiological function is understood. We consider as an example of the first goal a study that purports to demonstrate a principle of thermoregulation, but that interaction between students and instructor reveals the study's lack of an essential control. The second goal requires sufficient time for the publication to concretely validate its contribution(s). The purpose is to identify those essential properties of the selected paper that contributed to its having become a truly exemplary study. We present a 1957 paper by Dr. A. C. Burton (Am Heart J 54: 801-810, 1957) as an illustration and analyze the study with respect to those attributes that contributed to its lasting importance. These alternative approaches to introduce inexperienced students to the original literature can produce critical insight into the process and can help students inculcate essential practices, guiding them to more productive careers.

The slope of the log of power versus the log of frequency in the arterial blood pressure (BP) power spectrum is classically considered constant over the low-frequency range (i.e., “fractal” behavior), and is quantified by β in the relationship “1/ f^β.” In practice, the fractal range cannot extend to indefinitely low frequencies, but factor(s) that terminate this behavior, and determine β, are unclear. We present 1) data in rats ( n = 8) that reveal an extremely low frequency spectral region (0.083–1 cycle/h), where β approaches 0 (i.e., the “shoulder”); and 2) a model that 1) predicts realistic values of β within that range of the spectrum that conforms to fractal dynamics (∼1–60 cycles/h), 2) offers an explanation for the shoulder, and 3) predicts that the “successive difference” in mean BP (mBP) is an important parameter of circulatory function. We recorded BP for up to 16 days. The absolute difference between successive mBP samples at 0.1 Hz (the successive difference, or Δ) was 1.87 ± 0.21 mmHg (means ± SD). We calculated β for three frequency ranges: 1) 0.083–1; 2) 1–6; and 3) 6–60 cycles/h. The β for all three regions differed ( P < 0.01). For the two higher frequency ranges, β indicated a fractal relationship (β_6–60/h = 1.27 ± 0.01; β_1–6/h = 1.80 ± 0.16). Conversely, the slope of the lowest frequency region (i.e., the shoulder) was nearly flat (β_{0.083–1 /h} = 0.32 ± 0.28). We simulated the BP time series as a random walk about 100 mmHg with ranges above and below of 10, 30, and 50 mmHg and with Δ from 0.5 to 2.5. The spectrum for the conditions mimicking actual BP time series (i.e., range, 85–115 mmHg; Δ, 2.00) resembled the observed spectra, with β in the lowest frequency range = 0.207 and fractal-like behavior in the two higher frequency ranges (β = 1.707 and 2.057). We suggest that the combined actions of mechanisms limiting the excursion of arterial BP produce the shoulder in the spectrum and that Δ contributes to determining β.

Presenting a 15-s pulsed tone, the conditional stimulus (CS⁺), followed by 0.5-s tail shock, to a well-trained rat causes a sudden, but transient, pressor response (C₁). Blood pressure (BP) then drops before increasing again (C₂). A steady tone of the same frequency never followed by a shock (a discriminative stimulus, or CS⁻) evokes a C₁ but not a C₂ response. Experiment 1 tested the hypothesis that this BP response pattern does not depend on the nature of the tone (i.e., pulsed vs. steady) used for CS⁺ and CS⁻. The tones were reversed from the traditional paradigm, above, in nine rats. The C₁ BP increase for a steady-tone CS⁺ (+4.8 ± 1.9 mmHg, mean change ± SE) and a pulsed CS⁻ (+2.9 ± 1.3 mmHg) did not differ. Conversely, C₂ showed a clear discrimination (CS⁺: +5.1 ± 1.2 mmHg, CS⁻: +0 .7 ± 0.8 mmHg; P < 0.05). Experiment 2 tested the hypothesis that the C₁ and C₂ BP responses first appear at different times during training. On training day 1, five 15-s pulsed tones (CS⁺) were presented to each of 18 rats; the last tone was followed by a tail shock. Likewise, five steady CS⁻ tones never followed by shock were given. Training continued for 2 more days, with each CS⁺ followed by shock. At the end of day 2, CS⁺ evoked a C₁ BP response (+3.9 ± 0.9 mmHg) but no C₂ (+0.6 ± 0.4 mmHg, not significant vs. pretone). By the end of day 3, CS⁺ evoked a significant (vs. baseline) C₁ (+7.3 ± 1.4 mmHg) and C₂ (+3.3 ± 0.8 mmHg). Conversely, although CS⁻ evoked a C₁ response (3.5 ± 1.3 mmHg), there was no C₂ (+0.7 ± 0.5 mmHg; not significant). We conclude that 1) C₁ and C₂ are acquired at different rates, 2) early in training C₁ is an orienting response evoked by both tones, and 3) C₂ is only acquired as an animal learns to associate the CS⁺ tone with shock. This suggests that C₁ and C₂ are controlled by different processes in the brain.

This study quantified the effect of interrupting the descending input to the sympathetic preganglionic neurons on the dynamic behavior of arterial blood pressure (BP) in the unanesthetized rat. BP was recorded for ∼4-h intervals in six rats in the neurally intact state and in the same animals after complete spinal cord transection (SCT) between T₄ and T₅. In the intact state, power within the frequency range of 0.35–0.45 Hz was 1.53 ± 0.38 mmHg²/Hz (mean ± SD by fast Fourier transform). One week after SCT, power within this range decreased significantly ( P < 0.05) to 0.43 ± 0.62 mmHg²/Hz. To test for self-similarity before and after SCT, we analyzed data using a wavelet (i.e., functionally, a digital bandpass filter) tuned to be maximally sensitive to fluctuations with periods of ∼2, 4, 8, 16, 32, or 64 s. In the control state, all fluctuations with periods of ≥4 s conformed to a “self-similar” (i.e., fractal) distribution. In marked contrast, the oscillations with a period of ∼2 s (i.e., ∼0.4 Hz) were significantly set apart from those at lower frequencies. One day and seven days after the complete SCT, however, the BP fluctuations at ∼0.4 Hz now also conformed to the same self-similar behavior characteristic of the lower frequencies. We conclude that 1) an intact sympathetic nervous system endows that portion of the power spectrum centered around ∼0.4 Hz with properties (e.g., a periodicity) that differ significantly from the self-similar behavior that characterizes the lower frequencies and 2) even within the relatively high frequency range at 0.4 Hz self-similarity is the “default” condition after sympathetic influences have been eliminated.

This essay looks at the historical significance of three APS classic papers that are freely available online: Cannon WB and de la Paz D. Emotional stimulation of adrenal secretion. Am J Physiol 28: 64-70, 1911 ( http://ajplegacy.physiology.org/cgi/reprint/28/1/64 ). Cannon WB. The emergency function of the adrenal medulla in pain and the major emotions. Am J Physiol 33: 356-372, 1914 ( http://ajplegacy.physiology.org/cgi/reprint/33/2/356 ). Cannon WB. Studies on the conditions of activity in endocrine glands. V. The isolated heart as an indicator of adrenal secretion induced by pain, asphyxia and excitement. Am J Physiol 50: 399-432, 1919 ( http://ajplegacy.physiology.org/cgi/reprint/50/3/399 ).

68A realistic research experience is beneficial to undergraduate students, but it is often difficult for liberal arts colleges to offer this opportunity. We describe two approaches for developing and maintaining an interdisciplinary research program at small colleges. An active and continuing involvement of an individual with extensive research experience is an essential element in both. One model was developed by the faculty of Taylor University, Upland, IN and a research scientist who had retired from a major university to join the Taylor faculty as their first Research Professor. The school’s Science Research Training Program was initially funded by a modest endowment provided by interested alumni and by extramural grants awarded to the Research Professor and to the institution; the program now enjoys significant funding from diverse sources. Taylor is not located near any large research university and consequently supplies all resources required for the experiments and stipends for students pursuing projects full-time during the summer. The second model was developed by the faculty at Asbury College in Wilmore, KY, working with a scientist having a full-time appointment at the University of Kentucky and a part-time appointment at the college. In this approach, Asbury faculty may place their students for a period of training, often during the summer, in a laboratory of a cooperating host faculty at the University of Kentucky or other institution. The host faculty funds the research and pays a stipend to those students who work full-time during the summer. Relationships established between faculty at the College and at the University of Kentucky have been mutually beneficial. The success of both programs is evidenced by the students’ presenting their data at state and national scientific meetings, by their publishing their results in national journals, and by the undergraduate school faculty developing independent research programs.

The objective of this study was to determine how neurons within the right atrial ganglionated plexus (RAGP) and posterior atrial ganglionated plexus (PAGP) interact to modulate right atrial chronotropic, dromotropic, and inotropic function, particularly with respect to their extracardiac vagal and sympathetic efferent neuronal inputs. Surgical ablation of the PAGP (PAGPx) attenuated vagally mediated bradycardia by 26%; it reduced heart rate slowing evoked by vagal stimulation superimposed on sympathetically mediated tachycardia by 36%. RAGP ablation (RAGPx) eliminated vagally mediated bradycardia, while retaining the vagally induced suppression of sympathetic-mediated tachycardia (-83%). After combined RAGPx and PAGPx, vagal stimulation still reduced sympathetic-mediated tachycardia (-47%). After RAGPx alone and after PAGPx alone, stimulation of the vagi still produced negative dromotropic effects, although these changes were attenuated compared with the intact state. Negative dromotropic responses to vagal stimulation were further attenuated after combined ablation, but parasympathetic inhibition of atrioventricular nodal conduction was still demonstrable in most animals. Finally, neither RAGPx nor PAGPx altered autonomic regulation of right atrial inotropic function. These data indicate that multiple aggregates of neurons within the intrinsic cardiac nervous system are involved in sinoatrial nodal regulation. Whereas parasympathetic efferent neurons regulating the right atrium, including the sinoatrial node, are primarily located within the RAGP, prejunctional parasympathetic-sympathetic interactions regulating right atrial function also involve neurons within the PAGP.