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The systematic shift in time constants across vibrissae also generates a map of onset timing within SI that may provide relevant coding information for the behaving animal 100 mg viagra super active with visa, and that could increase the efficacy of input to an isofrequency column through enhanced neural synchrony generic 25mg viagra super active mastercard. If temporal cod- ing and not place coding is the relevant mechanism for texture extraction, vibrissa resonance may still play an essential role in the perception of these small amplitude, high frequency stimuli because these inputs would not otherwise be represented by a temporal code, or in any fashion, without this amplification. In these examples of fine temporal tuning, only a subset of the amplitudes of stimulation that evoked a mean firing rate increase, also showed high frequency following. The amplitude-dependence of temporal tuning can also be appreciated by examination of the inter-spike interval histograms in Figure 2. While higher amplitudes of stimulation evoked only intervals at the period of the stimulus, lower amplitudes of stimulation evoked intervals that were more likely to be multiples of the frequency period. This difference between the amplitudes necessary for mean firing rate increases and those necessary for temporal following parallels differences observed during auditory stimulation in the cat75 and vibratory stimulation of the monkey skin. They hypothesized that the larger amplitudes of stimu- lation required for primate frequency discrimination might, in contrast, reflect the larger amplitude of stimulation necessary to entrain neural firing. Vibrissa Resonance and the Volley Principle As suggested throughout this chapter, several of the questions posed in attempting to understand high frequency encoding in the vibrissa sensory system mirror those traditionally posed in study of the auditory system. The central debate that shaped and continues to influence the attempt to understand neural mechanisms of auditory perception has been recapitulated here. Specifically, can high frequency encoding be understood as a place code where the frequency content of a stimulus is determined from a spatial map of frequency established by the biomechanical transduction properties of the peripheral sensors, or, can the fine timing of neural activity, a temporal code, account for pitch perception? Most likely, these mech- anisms work in combination with predominance in different ranges of the percep- tual spectrum. As a solution to this challenge to temporal coding, Wever proposed the volley principle, suggesting that while any given neuron might not follow every cycle of a stimulus, different subpop- ulations within a group of neurons could fire in a phase-locked manner to different © 2005 by Taylor & Francis Group. The top graph shows a frequency tuning curve for a trigeminal unit, constructed by counting all evoked inter-spike intervals (ISIs), a measure that is functionally equivalent to the mean firing rate. The lower graph shows the count of ISIs at the driving period, indicating fine temporal following of the neuron. Numbers adjacent to each curve indicate the amplitude of vibrissa stimulation applied. Frequency tuning was observed in both the mean firing rate and in the fine timing of neural evoked activity.

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While methemoglo- who have become dependent on nitroglycerin have binemia does not follow therapeutic doses of organic ni- been reported to undergo angina generic 25mg viagra super active with visa, myocardial infarc- trates viagra super active 50mg with visa, it can be observed after overdosage or accidental tion, or even sudden death following removal from poisoning. Some of these patients showed symptoms of ischemic heart disease, even Cautions though their coronary arteriography was judged to be normal. Since it is possible that coronary vasospasm Chest pain that is not relieved by two or three tablets plays a role in the pathogenesis of angina that occurs within 30 minutes may be due to an acute myocardial in nitrate-dependent individuals, these patients should infarction. In addition, nitrate administration may result be cautioned to watch for increased chest pain when in an increase in intracranial pressure, and therefore, they withdraw from medication or discontinue their these drugs should be used cautiously in patients with exposure. Adverse Effects -Adrenoceptor Blocking Agents Vascular headache, postural hypotension, and reflex -Adrenoceptor blockade is a rational approach to the tachycardia are common side effects of organic nitrate treatment of angina pectoris, since an increase in sym- therapy. Fortunately, tolerance to nitrate-induced head- pathetic nervous system activity is a common feature in ache develops after a few days of therapy. Based on their ability to reduce potension and tachycardia can be minimized by proper oxygen demand, all -blockers tested so far have also dosage adjustment and by instructing the patient to sit been shown to be effective in the treatment of second- 17 Antianginal Drugs 201 ary angina. Administration of these compounds results and thereby attenuate the myocardial response to stress in a decrease in frequency of anginal attacks, a reduc- or exercise (Fig. The resting heart rate is reduced tion in nitroglycerin consumption, an increased exercise by propranolol, but not to the same extent as is the de- tolerance on the treadmill, and a decreased magnitude crease in exercise-induced tachycardia. Overall, propra- of ST segment depression on the electrocardiogram nolol reduces myocardial oxygen consumption for a during exercise. Although the mechanisms responsible angina in the United States include propranolol and for this antihypertensive effect are not completely un- nadolol (Corgard), compounds that block both 1- and derstood, they are thought to involve (1) a reduction in 2-adrenoceptors equally, while atenolol (Tenormin) cardiac output, (2) a decrease in plasma renin activity, and metoprolol (Lopressor) are cardioselective 1- (3) an action in the central nervous system, and (4) a re- receptor antagonists. Thus, propranolol may ex- ert a part of its beneficial effects in secondary angina by decreasing three of the major determinants of myo- Mechanism of Action cardial oxygen demand, that is, heart rate, contractility, The myocardial response to exercise includes an in- and systolic wall tension. These Propranolol and other -blockers also have been effects are mediated in part by the sympathetic nervous shown to produce an increase in oxygen supply to the system. The mechanism re- antagonize the actions of catecholamines on the heart sponsible for this effect is most likely related to the Afterload Preload Heart rate Contractility Stenosis diameter Wall tension Site of occlusion Collateral vessel diameter Transmural blood flow epicardial Ischemic area endocardial FIGURE 17. Because subendocardial By attenuating the cardiac response to exercise, propra- blood flow and flow distal to severe coronary artery nolol and other -blockers increase the amount of ex- stenosis occur primarily during diastole, this increase in ercise that can be performed before angina develops. Finally, there is evidence that - Propranolol is particularly indicated in the manage- blockers can inhibit platelet aggregation.