David W. Snyder

Bio: David W. Snyder is an academic researcher from Cornell University. The author has contributed to research in topics: Blood pressure & Baroreceptor. The author has an hindex of 5, co-authored 6 publications receiving 301 citations.

Chronic lability of arterial pressure produced by selective destruction of the catecholamine innervation of the nucleus tractus solitarii in the rat.

Abstract: The effects of selective destruction of the catecholamine innervation of the nucleus tractus solitarii (NTS) on arterial pressure (MAP) and heart rate (HR) were examined in unanesthetized rats in which 6-hydroxydopamine (6-OHDA), 1μl, was injected bilaterally into the nucleus at the level of the obex. Control rats received 1 fil of vehicle or were uninjected. Baroreceptor reflex activity was tested by measuring the reflex bradycardia in response to graded doses of phenylephrine. 6-OHDA, 2 μg, did not alter MAP or HR; 12 μg, a dose producing necrosis of NTS, resulted in the development within 4-6 hours of fulminating arterial hypertension and tachycardia. 6-OHDA, 4 fig, produced an elevation of MAP which returned to control levels by 48 hours without changing HR. By 6 hours, however, the arterial pressure became extremely labile. Lability of MAP in the absence of hypertension or change of HR persisted for the longest period of observation, 2 weeks. Baroreceptor reflex activity remained, although the sensitivity of the reflex was depressed. 6-OHDA, 4 μg, failed to produce histological damage to NTS. Biochemically, it resulted after 14 days in a reduction of the activity of dopamine β-hydroxylase, a specific marker of noradrenergic and adrenergic neurons, to 40% of control without altering the activity of choline acetyltransferase, a marker of cholinergic neurons. We conclude that selective removal of a substantial portion of the catecholamine innervation of the NTS, mostly noradrenergic, results in persistent lability without elevation of arterial pressure. The results suggest that the catecholamine innervation of NTS modulates rather than mediates baroreceptor reflexes, serving to maintain arterial pressure within narrow limits.

Chronic lability of arterial pressure produced by destruction of A2 catecholaminergic neurons in rat brainstem.

Abstract: SUMMARY The cardiovascular effects of electrolytic lesions of the A2 group of catecholaminergic neurons of the dorsal medulla were analyzed in chronically instrumented rats. A2 lesions resulted after 24 hours, in an enduring increase in lability (variability) and augmented reactivity of the arterial pressure during spontaneous or elicited behaviors, without a change in the average arterial pressure. Heart rate and its variability were unchanged. A2 lesions almost abolished the bradycardia elicited by acutely elevating arterial pressure with phenylephrine, but not the hypotension elicited under anesthesia by carotid sinus stretch. Lability of arterial pressure could not be attributed to damage to cardiovagal neurons. Vagal blockade with atropine or methylatropine did not alter the mean or variability of the arterial pressure. Lability of arterial pressure was produced only by damage to A2 neurons and not by lesions in the area postrema or by transection of commissural fibers of the nucleus tractus solitarii (NTS). Moreover, the magnitude of lability was correlated directly with the amount of damage to A2. A2 lesions resulted in a reduction of dopamine-/3-hydroxylase activity to 60% of control in the NTS. We conclude that destruction of A2 neurons produces persistent lability and exaggerated reactivity of arterial pressure as a consequence of partial removal of the noradrenergic innervation of the NTS. The results suggest that noradrenergic neurons of A2 serve to modulate baroreceptor reflexes in NTS. The observation that lability of arterial pressure can occur in the absence of changes of average arterial pressure suggests distinctive anatomical networks subserving phasic and tonic control of the arterial pressure in the brainstem. Circ Res 46: 842-853, 1980

Brain lesions and hypertension: chronic lability and elevation of arterial pressure produced by electrolytic lesions and 6-hydroxydopamine treatment of nucleus tractus solitarii (NTS) in rat and cat.

Abstract: Publisher Summary This chapter attempts to produce experimental neurogenic-hypertension in laboratory animals by electrolytic and chemical lesions of the brain It demonstrates that it is possible to produce chronic hypertension by lesions of nucleus of the tractus solitarii (NTS), thereby validating the hypothesis that central neural imbalances can result in hypertension The chapter also presents the studies demonstrating that selective destruction of the noradrenergic innervation of NTS by the drug 6-hydroxydopamine (6-OHDA), which selectively destroys noradrenergic terminals, can result in the development of marked lability of the arterial pressure This would suggest that the defects of chemical neurotransmission within the central nervous system (CNS) could possibly contribute to the conditions favoring the development of hypertension It is concluded that chronic neurogenic hypertension can result from imbalances in the CNS that result in disinhibition of sympathetic vasomotor outflow Specific biochemical defects of neurotransmitter systems, particularly of the noradrenergic innervation of the NTS, could possibly lead over time to the development of hypertension

Regional distribution of blood flow during arterial hypertension produced by lesions of the nucleus tractus solitarii in rats.

Abstract: Changes in the fractional distribution of cardiac output (FF), organ blood flow, and regional vascular resistance were measured by the isotope dilution technique of Sapirstein using 86Rb as indicator in unanesthetized rats during acute arterial hypertension produced by bilateral lesions of the nucleus tractus solitarii (NTS). After NTS lesions, the FF was significantly reduced in skin, muscle, and colon, increased in ventricular myocardium, spleen, and adrenal glands, and was unchanged elsewhere. Because of a marked reduction in cardiac output (CO) during hypertension, the absolute organ blood flow (FF X CO) was reduced in lesioned rats to 30-40% of control in skin, muscle, and colon and between 60% and 75% of control in most of the remainder of the gastrointestinal tract and renal cortex; it was unchanged in myocardium and endocrine glands. Resistance was substantially increased (4- to 6-fold) in skin, muscle and colon but was only moderately increased (1.5- to 2.5-fold) in the remaining organs. The results indicate that, while NTS lesions will increase resistance in most vascular beds, the response is unequally distributed, influencing skin, muscle, and colon disproportionately to other tissues. Because of an interaction between a reduction in CO and little autoregulation, blood flow is reduced primarily in skin, muscle, and colon. The pattern of redistribution of CO was consistent with the interpretation that NTS hypertension results from interrupting baroreceptor reflexes centrally. The pattern of redistribution of blood flow in rats with NTS lesions differs from that produced by deoxycorticosterone acetate-salt and renal ischemia.

Different projections of the central amygdaloid nucleus mediate autonomic and behavioral correlates of conditioned fear

Abstract: The purpose of the present study was to determine whether lesions of areas projected to by the central amygdaloid nucleus (ACE) would disrupt the classical conditioning of autonomic and/or behavioral emotional responses. The areas studied included 3 projection targets of the ACE: the lateral hypothalamic area (LH), midbrain central gray (CG) region, and bed nucleus of the stria terminalis (BNST). Lesions were made either electrolytically or by microinjection of ibotenic acid, which destroys local neurons without interrupting fibers of passage. Two weeks later, the animals were classically conditioned by pairing an acoustic stimulus with footshock. The next day, conditioned changes in autonomic activity (increases in arterial pressure) and emotional behavior ("freezing," or the arrest of somatomotor activity) evoked by the acoustic conditioned stimulus (CS) were measured during extinction trials. Electrolytic and ibotenic acid lesions of the LH interfered with the conditioned arterial pressure response, but did not affect conditioned freezing. Electrolytic lesions of the rostral CG disrupted conditioned freezing but not conditioned changes in arterial pressure. Ibotenic acid injected into the rostral CG reduced neither the arterial pressure nor the freezing response. Injection of ibotenic acid in the caudal CG, like electrolytic lesions of the rostral CG, disrupted the freezing, but not the arterial pressure response. Injection of ibotenic acid into the BNST had no effect on either response. These data demonstrate that neurons in the LH are involved in the autonomic, but not the behavioral, conditioned response pathway, whereas neurons in the caudal CG are involved in the behavioral, but not the autonomic, pathway. Different efferent projections of the central amygdala thus appear to mediate the behavioral and autonomic concomitants of conditioned fear.

Distribution of Pre-Pro-Glucagon and Glucagon-Like peptide-1 Receptor Messenger RNAs in the Rat Central Nervous System

Abstract: Glucagon-like peptide-1 (GLP-1) is derived from the peptide precursor pre-pro-glucagon (PPG) by enzymatic cleavage and acts via its receptor, glucagon-like peptide-1 receptor (GLP-1R). By using riboprobes complementary to PPG and GLP-1R, we described the distribution of PPG and GLP-1R messenger RNAs (mRNAs) in the central nervous system of the rat. PPG mRNA-expressing perikarya were restricted to the nucleus of the solitary tact or to the dorsal and ventral medulla and olfactory bulb. GLP-1R mRNA was detected in numerous brain regions, including the mitral cell layer of the olfactory bulb; temporal cortex; caudal hippocampus; lateral septum; amygdala; nucleus accumbens; ventral pallium; nucleus basalis Meynert; bed nucleus of the stria terminalis; preoptic area; paraventricular, supraoptic, arcuate, and dorsomedial nuclei of the hypothalamus; lateral habenula; zona incerta; substantia innominata; posterior thalamic nuclei; ventral tegmental area; dorsal tegmental, posterodorsal tegmental, and interpeduncular nuclei; substantia nigra, central gray; raphe nuclei; parabrachial nuclei; locus ceruleus, nucleus of the solitary tract; area postrema; dorsal nucleus of the vagus; lateral reticular nucleus; and spinal cord. These studies, in addition to describing the sites of GLP-1 and GLP-1R synthesis, suggest that the efferent connections from the nucleus of the solitary tract are more widespread than previously reported. Although the current role of GLP-1 in regulating neuronal physiology is not known, these studies provide detailed information about the sites of GLP-1 synthesis and potential sites of action, an important first step in evaluating the function of GLP-1 in the brain. The widespread distribution of GLP-1R mRNA-containing cells strongly suggests that GLP-1 not only functions as a satiety factor but also acts as a neurotransmitter or neuromodulator in anatomically and functionally distinct areas of the central nervous system.

Equipotentiality of thalamo-amygdala and thalamo-cortico-amygdala circuits in auditory fear conditioning

Abstract: The goal of the present study was to examine the contribution of thalamo-amygdala and thalamo-cortico-amygdala projections to fear conditioning. Lesions were used to destroy either the thalamo-cortico-amygdala projection, the thalamo-amygdala projection, or both projections, and the effects of such lesions on the acquisition of conditioned fear responses (changes in arterial pressure and freezing behavior) to a tone paired with footshock were measured. In each group of animals examined, a large lesion of the acoustic thalamus, including all nuclei of the medial geniculate body and adjacent portions of the posterior thalamus, was made on one side of the brain to block auditory transmission to the forebrain at the level of the thalamus on that side. In this way, experimental lesions could be made on the contralateral side of the brain. Thus, animals with thalamo-amygdala pathway lesions received a large lesion of the acoustic thalamus on one side. Contralaterally, only the nuclei that project to the amygdala (the medial division of the medial geniculate body, the posterior intralaminar nucleus, and the suprageniculate nucleus) were selectively destroyed, leaving much of the thalamo-cortico-amygdala projection intact. For thalamo-cortico-amygdala pathway lesions, the acoustic thalamus was destroyed on one side and temporal and perirhinal cortices were ablated contralaterally. In these animals, thalamo-amygdala projections were intact on the side of the cortical lesion. Destruction of either pathway alone had no effect on auditory fear conditioning. However, combined lesions of the two sensory pathways disrupted conditioning.(ABSTRACT TRUNCATED AT 250 WORDS)