David Whitehorn

Cardiovascular responses elicited by electrical stimulation of the amygdala central nucleus in the rabbit

Recent behavioral and anatomical evidence suggests the involvement of the amygdala central nucleus projection to medullary cardioregulatory nuclei in the expression of conditioned bradycardia during aversive Pavlovian conditioning in the rabbit 6,7,11,15. The present study sought to determine the extent to which electrical stimulation of the central nucleus produces bradycardia in the rabbit, and the extent to which any bradycardia elicited varies with stimulation at sites within as opposed to adjacent to the medial component of the central nucleus, the component from which the projection to cardioregulatory nuclei originates. Over 900 sites in 30 rabbits anesthetized with alpha-chloralose were explored. Monopolar stimulation (30-100 Hz; 0.5 ms pulse duration; 5.0 s train duration; 100-500 microamperemeter) at sites within the central nucleus produced bradycardia and depressor responses. Maximum bradycardia was produced from sites within the anterior, medial component of the nucleus. This response usually began within one second of stimulus onset, reached peak magnitude within two seconds of stimulus onset and in many instances was followed by a slight tachycardia following stimulus termination. The accompanying depressor responses occurred at longer latencies than the bradycardia responses. The responses persisted following artificial ventilation and immobilization by Flaxedil and were attenuated by i.v. injections of atropine methylnitrate. While bradycardia and depressor responses were elicited from sites immediately dorsal, ventral and lateral to the medial central nucleus, component. The results are consistent with previous evidence which suggests a contribution for the central nucleus in the expression of cardiovascular responding during aversive Pavlovian conditioning in the rabbit.

Effect of hypothalamic stimulation in spontaneously hypertensive and Wistar-Kyoto rats

This study was undertaken to determine if central nervous system differences in blood pressure regulation exist between spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) controls. Central control mechanisms were examined by observing the effects of posterior hypothalamic (PH) stimulation upon preganglionic sympathetic activity in 14--18 week old SHR and WKY rats. A bipolar, concentric electrode was stereotaxically placed in the PH. Stimulation was delivered at 20, 60 and 100 Hz (3-sec duration, 0.1 msec pulse width) at a voltage twice that producing an increase in blood pressure (less than 5 mm Hg) at 60 Hz. Sympathetic activity was recorded from a portion of the splanchnic nerve just distal to the diaphragm. Blood pressure was measured from a femoral artery catheter. SHR responded with greater increases in sympathetic activity than WKY; the differences were statistically significant at 60 and 100 Hz. SHR also responded with significantly greater increases in blood pressure at all frequencies of stimulation. To determine if the enhanced sympathetic response to PH stimulation seen in adult SHR is an intrinsic difference rather than secondary to sustained hypertension, we maintained SHR normotensive from four weeks of age with antihypertensive drug therapy (clonidine or hydralazine). Chronically treated animals were then tested at 14--18 weeks of age while on antihypertensives or four days after drug discontinuance. Sympathetic and blood pressure responses to PH stimulation were significantly greater in SHR maintained normotensive than untreated or chronically treated WKY. These data support the concept that a central factor is involved in the etiology of hypertension in the SHR.

Age, sex and strain differences in activity and habituation in SHR and WKY Rats

The highly inbred strain of Wistar-Kyoto spontaneously hypertensive rat (SHR) and its normotensive, genetic control (WKY) were examined with respect to strain differences in spontaneous activity scores in a novel environment (small activity cage) and in ability to habituate to that environment. These behaviors were examined in experimentally naive rats, 197 SHR and WKY, males and females, at varying ages from 4 to 56 weeks, in order to determine whether there are sex and age differences in addition to the well-known strain differences in these behaviors. Total activity scores, determined in a 15 min test in the activity cage, were higher in SHR than WKY rats; females were significantly more active than males in either strain, and activity scores varied significantly with age both within strains and between strains. Ability to habituate to the test cage was determined by repeating the 15 min activity test at hourly intervals for three additional trials on the same day. The results indicate that the SHR, males and females and at all ages tested, habituate poorly if at all to the test cage as compared with WKY rats. Moreover, despite the variability of baseline activity scores (first trial) observed across ages, sexes and strains, the habituation patterns of either strain remained relatively fixed throughout the first year of life.

Independence of blood pressure and locomotor hyperactivity in normotensive and genetically hypertensive rat

The spontaneously hypertensive rat (SHR) exhibits locomotor hyperactivity in comparison to its normotensive progenitor Wistar-Kyoto (WKY) strain. We asked whether the hyperactive behavior was a direct consequence of elevated blood pressure in the hypertensive rat. Three experimental protocols were used to chronically alter blood pressure. In the first protocol, a group of adult SHRs was given hydralazine (20 mg/kg/day) in their drinking water to lower blood pressure. These animals exhibited a significant decrease in blood pressure, but no change in locomotor activity. In the second protocol, young SHRs (4 weeks of age) were treated with the same dosage of hydralazine until 16 weeks of age. Blood pressure was significantly decreased in these animals with no change in locomotor activity. In the third protocol, normotensive WKY and Sprague-Dawley (SD) rats were made hypertensive with unilateral renal clips. The resulting increase in blood pressure in these animals did not alter locomotor activity. These results suggest that locomotor hyperactivity is an inherent property of the SHR and is independent of blood pressure.

Locomotor activity, auditory startle and shock thresholds in spontaneously hypertensive rats ☆

A group of SHRs and a group of WKY normotensive controls were compared sequentially on open-field behavior, Y-maze activity, responsiveness and habituation of the auditory startle response, and shock thresholds. In the open field and Y maze the SHRs were more active than the WKYs, but the locomotor activity of the SHRs decreased more within sessions. However, the SHRs could be described as showing more, less or the same between-session habituation depending upon the apparatus and the portion of the session analyzed. The SHRs were less responsive than controls on the auditory startle response measure, and they did not differ from controls on startle-response habituation. The SHRs were less responsive than controls at low shock levels but more responsive at high shock levels. The relationship between SHRs and WKYs on the responsiveness dimension depended upon the modality and intensity of the stimulus, the response characteristics of the test situation, and the time sample of behavior taken.

Genetically related rats with differences in hippocampal uptake of norepinephrine and maze performance.

The spontaneously hypertensive rat (SHR) and its progenitor strain, the Wistar-Kyoto (WKY) display marked differences in brain catecholamines and behavior. The behavioral differences are suggestive of alterations in hippocampal function and, in particular, the noradrenergic input to the hippocampus. To test these hypotheses we have analyzed the performance of the SHR and WKY in a spatial memory maze task that is specific to hippocampal function and determined the kinetics of norepinephrine (NE) uptake in synaptosomal preparations of the hippocampus. We have found that WKYs exhibit an abnormally strong bias tendency in T-maze arm preference that influences the rate of acquisition and the final level of maze performance. We have also found differences in noradrenergic uptake in hippocampal synaptosomes. WKYs exhibit higher NE uptake rates and higher kinetic constants for NE uptake when compared with SHRs, suggesting that strain differences in noradrenergic function may contribute to the observed behavioral differences.

Enhanced preganglionic sympathetic nerve responses in spontaneously hypertensive rats

Sympathetic nerve responses to posterior hypothalamic stimulation were recorded from the preceliac splanchnic nerve in spontaneously hypertensive rats (SHR) and normotensive, Wistar-Kyoto rats (WKY) following interruption of the baroreceptor reflex. Responses to identical stimulation were then recorded following ganglionic blockade with hexamethonium. The enhanced preganglionic sympathetic nerve responses measured in SHR indicate that the sympathetic hyperresponsiveness strain occurs, at least in part, at a site within the central nervous system.

Population analysis of single units in the cuneate nucleus of the cat

Abstract Population analysis has been used to investigate the properties of cells in the cuneate nucleus of the chloralose-anesthetized cat. Postsynaptic units were grouped on the basis of the maximum frequency following to ipsilateral superficial radial nerve stimulation, the degree of convergence onto cells from central and peripheral sources, and the response to natural stimulation of the ipsilateral forelimb. The groups were analyzed further on the basis of depth in the brainstem, initial spike latency, and variability in the initial spike latency in response to stimulation of the ipsilateral forelimb. Maximum order to the data resulted when the cells were grouped on the basis of maximum frequency following ability. The possible role of the defined cell groups in production of primary afferent depolarization (PAD) was examined by constructing simulated PAD time course curves. Both a rapidly rising time course curve, typical of ipsilateral forelimb activation, and a slowly rising curve, typical of “off-focus” activation, could be obtained by linearly summing unit depolarizations in a temporal pattern defined by measured spike latencies to the appropriate input. This, and other evidence, suggest that the observed properties of cuneate inhibition can be accounted for by the activity of cells within the cuneate nucleus. A wiring diagram for cuneate inhibition circuitry is presented.

Quantitative characteristics of inhibition in the cuneate nucleus of the cat

Abstract Several properties of inhibition in the cuneate nucleus were investigated as an aid in deriving cuneate circuitry. Inhibition was examined by measuring changes in primary afferent terminal depolarization (PAD) and in the size of evoked medial lemniscal activity. Inhibition was produced by stimulation of several peripheral and central sites. Quantitative measurements were made of the inhibitory time course and degree of facilitation to conditioning trains of different lengths. The data suggest a dual organization of inhibition, dependent upon the conditioning site and characterized by the inhibitory time course. Additional information was derived from PAD measurements following simultaneous stimulation of two conditioning sites and from an investigation of a cortico-cuneate feedback loop. The proposed two inhibitory systems appear to converge for simultaneous activation did not produce simple summation of PAD. These results were substantiated when PAD was measured from single, identified cutaneous fibers. The time course of single fiber PAD was similar to that in a whole nerve preparation. Single fibers could be depolarized by conditioning several sites and with no apparent fiber class dependence. Several models of inhibitory circuitry are presented, and the features that must be taken into account are discussed.

Differences in transmission through the dorsal column nuclei in spontaneously hypertensive and Wistar Kyoto rats

The medical lemniscal evoked potential in response to a range of footshock intensities was recorded in spontaneously hypertensive (SHR) and Wistar Kyoto rats (WKY). Input-output (I-O) relationships were constructed as the percent of maximum response at each intensity. The SHR had a steeper I-O relationship than did the WKY. This difference was also evident when SHR maintained normotensive from weaning with hydralazine were compared with identically treated WKY. The treatment itself steepened the I-O relationship of the SHR while leaving that of the WKY unchanged. These results indicate an inherent hyperresponsiveness in the SHR dorsal column nuclei and an inhibitory effect of elevated blood pressure on transmission through these nuclei.