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Biomedical subjects

G L Gebber

Publications and source records attributed to G L Gebber.

At least 91 records · Page 5Linked to original sources

Sympathetic-related activity of brain stem neurons in baroreceptor-denervated cats.

A search was initiated in baroreceptor-denervated cats for brain stem neurons with activity patterns related to inferior cardiac sympathetic nerve discharge (SND). Neurons whose spontaneous discharges were followed by increases or decreases in SND fell into two categories. S unit discharges were related to SND but not electroencephalogram (EEG) activity. The activity of SE units was related to SND and EEG activity. The anatomic distribution of S and SE units was similar to that previously reported [Barman and Gebber, Am J. Physiol. 240 (Regulatory Integrative Comp. Physiol. 9): R335-R347, 1981] for units with activity patterns related to SND in baroreceptor-innervated cats. Autocorrelograms of S unit discharges and SND contained the same rhythm (2-6 cycles/s). This rhythm was different from that contained in SE unit discharges and EEG activity in experiments in which SND and cortical activity were not related. In other experiments, sympathetic nerve and cortical rhythms were locked to each other. SE units but no S neurons were located in these cats, and the rhythm contained within the autocorrelograms of their discharges was the same as that observed in SND and EEG activity. A model of brain stem networks, which govern the discharges of sympathetic nerve, is presented on the basis of these data.

Action Potentials↗

Central oscillators responsible for sympathetic nerve discharge.

The current state of knowledge concerning central mechanisms responsible for the generation of background discharges in sympathetic nerves is examined. It is apparent from recent investigations that the classic concept of a randomly discharging and diffusely organized central network onto which rhythms (cardiac- and respiratory-related) are imposed by extrinsic inputs has not passed the test of time. Rather, brain stem as well as spinal networks that govern the discharges of sympathetic nerves are inherently capable of rhythm generation. Sympathetic nerve rhythms inherent to the central nervous system imply the existence of neuronal circuits that are capable of oscillatory activity. Central oscillators provide a mechanism for synchronization of the activity of populations of sympathetic neurons in the absence of periodic input from sources extrinsic to the central nervous system. Indeed, the thesis is developed that, rather than creating rhythms in sympathetic nerve discharge, the function of periodic input from extrinsic sources such as the baroreceptors is to entrain rhythms of central origin. Finally, the problems associated with the identification of neuronal types that comprise central oscillators which govern the discharges of sympathetic nerves are discussed.

Action Potentials↗

Rhythmogenesis in the sympathetic nervous system.

This paper reviews work performed in our laboratory on the origin of the 2--6 cycles per second (c/s) rhythm in the discharges of preganglionic and postganglionic sympathetic nerves of the cat. It was demonstrated that the 2--6 c/s rhythm does not result as the simple consequence of the baroreceptor reflexes. Furthermore, the rhythm persisted in the baroreceptor-denervated cat after midcollicular decerebration, but not after high spinal transection. These observations indicate that brain stem networks are inherently capable of generating a 2--6 c/s rhythm in sympathetic nerve discharge (SND). Two forms of the rhythm were observed in the baroreceptor denervated and decerebrate cat--simple and complex. The complex form is characterized by variability of sympathetic nerve slow wave occurrence in the 2--6 c/s band. A model for the genesis of the complex form of the rhythm is presented. It is proposed that the brain stem sympathetic network is composed of a number of oscillators that are directly coupled and/or receive common inputs. Each oscillator primarily drives a separate group of preganglionic neurons. Moreover, the lead oscillator and thus the sequence of activation of the coupled oscillators changes from cycle to cycle. Shifts in the leading focus of brain stem activity (i.e., lead oscillator) presumably account for the complex rhythm in SND. The functional implications of this model are discussed.

Animals↗

Picrotoxin- and bicuculline-sensitive inhibition of cardiac vagal reflexes.

Transmission in the cardiac vagal reflex pathway can be inhibited by stimulation of the hypothalamic defense region or somatic afferent nerves. A pharmacological analysis of inhibitory modulation of reflex vagal bradycardia was undertaken in the present study. Picrotoxin (0.5--1.5 mg/kg i.v.) or bicuculline (0.5--1.5 mg/kg i.v.) produced a dose-related blockade of inhibition of reflex vagal bradycardia elicited by stimulation of the lateral hypothalamus or branches of the brachial plexus in spinal (C1 or C8 transected) cats. In contrast, strychnine and pentylenetetrazol failed to change the heart rate responses produced by stimulation of the hypothalamus or brachial plexus afferents. Picrotoxin and bicuculline also blocked inhibition of reflex vagal bradycardia produced by stimulation of the inferior olive in decerebrate spinal cats. This observation supports the contention that these agents act in the brain stem to block inhibitory modulation of reflex vagal bradycardia. In addition, picrotoxin and bicuculline lowered basal heart rate in spinal cats but not in decerebrate spinal cats. This observation suggests that tonic suprabulbar inhibition of reflex vagal bradycardia also is sensitive to blockade by picrotoxin and bicuculline.

Afferent Pathways↗

Spinal interneurons in the baroreceptor reflex arc.

The zona intermedia of the cat thoracic spinal cord was explored with metal microelectrodes in an attempt to locate interneurons within the pathway that mediates the spinal component of baroreceptor-induced sympathoinhibition. Twenty-nine neurons whose discharges were interrupted during occlusion of the common carotid arteries were found in the vicinity of the intermediomedial nucleus (IMM). The spontaneous discharges of 10 of these units were correlated in time with the R wave of the ECG. The pattern of R-wave locking of spinal unitary discharge was similar to that for some neurons in the nucleus of the tractus solitarius (NTS; primary site of baroreceptor fiber termination). In addition, spinal units, whose discharges were interrupted during carotid artery occlusion, were activated by stimulation of depressor sites in NTS. These observations suggest that bulbospinal fibers of the baroreceptor reflex arc terminate on and excite interneurons in the vicinity of IMM. It is postulated that these neurons directly inhibit components of sympathoexcitatory pathways located in the intermediolateral spinal nucleus. Furthermore, it was demonstrated that the inhibitory interneurons receive auxiliary input from sympathetic afferents in the inferior cardiac nerve.

Action Potentials↗

Differential effect of baroreceptor reflexes and clonidine on frequency components of sympathetic discharge.

The effects of the baroreceptor reflexes and clonidine on the 3 and 10 Hz components of spontaneously occurring renal sympathetic nervous discharge (SND) were studied in the cat. The proportion of 3 : 10 Hz SND was assessed by selective filtering and integration of activity in the 2-4 Hz and 9-11 Hz frequency bands. Baroreceptor denervation increased activity in both frequency bands while significantly lowering the 3 : 10 Hz ratio. Baroreceptor reflex activation (i.v. phenylephrine) decreased activity in both frequency bands while significantly increasing the 3 : 10 ratio. Clonidine (4-20 mug/kg, i.v.) affected the 3 : 10 Hz ratio of SND in a manner similar to baroreceptor reflex activation. These results indicate that the 3 and 10 Hz components of SND, both of which have been previously shown to be inherent to the central vasomotor system, are differentially affected by the baroreceptor reflexes and clonidine. It is concluded that it is possible to characterize certain cardiovascular states with respect to the 3 : 10 Hz ratio of SND.

Animals↗

Basis for phase relations between baroreceptor and sympathetic nervous discharge.

The phase relations between the cardiac cycle and sympathetic nervous discharge (SND) were studied with an average-response computer in the anesthetized cat. Maximum SND occurred during early diastole at heart rates between 3 and 4 beats/s. Dramatic shifts in the phase relations between SND and the cardiac cycle accompanied the decrease in heart rate produced by stimulation of the distal end of the cut right vagus nerve. The point of maximum SND was shifted from early diastole to near peak systole and then into the late diastolic phase of the preceding cardiac cycle as heart rate was progressively lowered to 2 beats/s. These observations indicate that synchronization of SND during each cardiac cycle is not the simple consequence of the waxing and waning of baroreceptor nerve activity. Rather, 1:1 locking of bursts of SND to the cardiac cycle is explained on the basis of entrainment by the baroreceptor reflexes of a sympathetic rhythm of central origin. An inhibitory-phasing hypothesis is proposed to account for entrainment. In addition, two components (spinal and brainstem) of sympathoinhibition associated with the pulse-synchronous discharge of the carotid sinus nerve were revealed when the 1:1 relationship between bursts of SND and the cardiac cycle was disrupted at heart rates below 2 beats/s.

Animals↗

Identification and discharge patterns of spinal sympathetic interneurons.

Sympathetic interneurons, in the vicinity of the intermediolateral cell column of the cat thoracic spinal cord, were identified by determining whether the probability of spontaneously occurring unitary discharge was correlated in time with the R wave of the ECG. Fifteen units which could not be antidromically activated by stimulation of the cervical sympathetic nerve exhivited a positive post-R wave relationship. The discharge patterns of these cells were distinctly different from those of antidromically identified preganglionic neurons. The interneurons discharged spontaneously in bursts with short interspike intervals (less than 20 ms). Preganglionic neurons rarely discharged more than once during a cardiac cycle. Single shocks applied to medullary pressor sites evoked a train of spikes in the interneurons. Preganglionic units usually discharged only once to medullary pressor stimulation. Electrial activation of medullospinal inhibitory tracts suppressed the discharges of both interneurons and preganclionic units. This observation indicates that spinal inhibition is exerted at an interneuronal level within sympathoexictatory pathways. No evidence was found for the existence of inhibitory interneurons in the intermediolateral cell column. This study demonstrated that the post-R wave time interval histogram in combination with a test for antidromic activation can be used to differentiate between spinal sympathetic internuerons and preganglionic cells.

Animals↗

Basis for synchronization of sympathetic and phrenic nerve discharges.

The basis for the relationship between the discharges in the external cartized cats that were vagotomized, paralyzed, and artificially ventilated. Ive discharge (with the period of the cycle of phrenic nerve activity) is extrinsically imposed on central sympathetic networks by elements of the brainstem respiratory oscillator. However, a number of observations made in the present study contradict this view. First, changes in respiratory rate were accompanied by dramatic shifts in the phase relations between sympathetic and phrenic nerve discharge. Second, slow oscillations of sympathetic and phrenic nerve discharge were not always locked in a 1:1 relation. Third, the slow sympathetic rhythm persisted when respiratory rhythmicity disappeic components of sympathetic and phrenic nerve activity are generated by in

Animals↗

Basis for late expiratory spinal inhibition of phrenic nerve discharge.

The relationship between spinal inhibition of phrenic nerve activity and thoratic expiratory motoneuronal discharge was studied in chloralose-anesthetized and unanesthetized decerebrate cats. The amplitude of the phrenic nerve response elicited by singleshocks applied to descending tracts in the second cervical spinal segment progressively fell during the late expiratory phase of the central respiratory cycle. The depression resulted, at least in part, from active spinal inhibition since the spina-to-phrenic evoked response was smaller in late expiration than after C'1 spinal transection. Inhibition of the spinal-to-phrenic evoked was time-locked to the spontaneousburst of activity recorded from the eigth internal intercostal nerve. The degree of inhibition of the spinal-to-phenic evoked discharge was directly related to theamplitude of spontaneously occurring internal intercostal nerve activity. A similiarrelationship was observed when internal intercostal nerve activity and spinal inhibitionof phrenic discharge were evoked by stimulation of the superior laryngeal nerve. It is concluded htat late expiratory spinal inhibition of phrenic discharge was dependent on those neural events responsible for the activation of thoracic expiratory motoneurons.

Animals↗