Edward B. Kirsten

A feline decerebration technique with low mortality and long-term homeostasis

Abstract A technique is described which details simple and rapid surgical procedures for an acute midcollicular decerebration in the adult cat. This decerebration procedure includes a bilateral ligation of the external carotid arteries and is performed under halothane anesthesia. Mortality resulting from this procedure is less than 5%. Thus, a long-term, homeostatically stable decerebrate preparation is obtained in most experiments. Within one hour postdecerebration, the experimental animal exhibits values of respiratory tidal volume, frequency, end-expired CO 2 partial pressure and mean arterial blood pressure which approximate those of the unanesthetized, intact cat.

Characteristics and response differences to iontophoretically applied norepinephrine, D-amphetamine and acetylcholine on neurons in the medial and lateral vestibular nuclei of the cat

Midcollicular decerebrate cats, with their cerebellum removes, were tested with controlled acceleratory motion in order to identify neurons in the medial vestibular nucleus (MVN) and lateral vestibular nucleus (LVN) which responded to a motion stimulus. Five-barredled micropipettes were used to record single neuron activity and to apply norepinephrine (NE), d-amphetamine and acetylcholine (ACh). These agents were studied on spontaneously firing cells which responded to a motion stimulus and others which were in the MVN were inhibited by NE and d-amphetamine but were unaffected by iontophoresis of the alpha-adrenergic blocking agent phentolamine or the beta-antagonists, MJ-1999 or propranolol. In the LVN a majority of the cells tested were excited by NE and d-amphetamine. NE excitation in the LVN was antagonized by phentolamine but not by MJ-1999 or propranolo. Cats pretreated with reserpine to deplete brain catechlamines showed typical responses to NE BUT IONTOPHORESIS OF D-AMPHETAMINE WAS WITHOUT EFFECT. Unlike the differential sensitivity observed for NE, ACh excited most cells in both the MVN and LVN. NE and ACh produced similar responsed on vestibular neurons modulated by motion and those not responsive to motion. These observations suggest that NE-containing terminals are in close proximity to the vestibular neurons which were tested and further implicate both NE and ACh as neurotransmitters in afferent pathways to the vestibular nuclei.

Alteration of medullary respiratory unit discharge by iontophoretic application of putative neurotransmitters.

1 Cats with midcollicular decerebration were vagotomized, paralyzed and artificially ventilated. Phrenic nerve activity was recorded as an index of central respiratory rhythm. Medullary respiratory neurones and non‐respiratory cells located in approximation to the ventral respiratory nucleus were tested for their responsiveness to iontophoretically applied γ‐aminobutyric acid (GABA), acetylcholine (ACh) and glutamate. 2 GABA tended to inhibit, whereas ACh and glutamate excited activity both of respiratory and non‐respiratory units. Some phase‐spanning respiratory unit activities were converted to phasic discharge patterns linked to either inspiration or expiration concomitant with application of low GABA doses. Appropriate applications of GABA also resulted in a complete cessation of the respiratory or non‐respiratory neuronal activities. 3 While application of ACh or glutamate induced continuous firing in phasic, phase‐spanning respiratory neurones, the periodic discharge patterns of inspiratory or expiratory units was not altered by ACh or, in many instances, by glutamate. Only at high doses of glutamate was the phasic discharge of some inspiratory or expiratory units converted to tonic activity. 4 These observations suggest that strong inhibitory processes serve to maintain the phasic firing pattern of respiratory units. These data also support the concept that active‐inhibitory phase‐switching mechanisms serve to define respiratory rhythmicity.

Iontophoretic studies of histamine and histamine antagonists in the feline vestibular nuclei

The activity of single neurons in the vestibular neuronal complex of midcollicular decerebrate, decerebellectomized cats were recorded and their responsiveness to iontophoretically applied histamine and other agents determined. The majority of the cells tested were inhibited by iontophoresis of histamine while 24% were excited by this agent. Neurons exhibiting inhibitory responses were widely distributed throughout the four vestibular nuclei and adjacent reticular formation whereas excitatory responses to histamine were obtained mainly in the region of the lateral vestibular nucleus. The H2-receptor blocking agents metiamide and cimetidine were examined as to their actions on spontaneously firing cells and cells affected by histamine. Metiamide was selective in blocking histamine-induced inhibition but not excitation while cimetidine was ineffective in blocking either response. These results suggest that histamine has both inhibitory and excitatory actions on brain stem neurons and metiamide is an effective antagonist of histamine-induced inhibition.

PRENYLAMINE‐INDUCED CONTRACTURE OF FROG SKELETAL MUSCLE

1 Experiments were performed to determine the influence of prenylamine on excitation‐contraction coupling in frog sartorius muscle. 2 Prenylamine (0.2‐1.0 mM) produced a biphasic contracture in skeletal muscle characterized by an initial phasic and subsequent tonic contracture. 3 Neither dantrolene nor procaine blocked the prenylamine‐induced contracture. Pretreatment with 100 mM K+ blocked the phasic but not the tonic component of the prenylamine contracture. 4 Prenylamine produced a sustained increase in 45Ca efflux at all concentrations that produce contracture. These concentrations of prenylamine also depressed the action potential, muscle twitch and resting potential. 5 Low concentrations of prenylamine (0.05 mM) which produced neither contracture, 45Ca efflux nor 45Ca influx, depressed the action potential, muscle twitch and K+ contracture. 6 The results suggest that prenylamine not only alters calcium mobility but also membrane permeability to other ions.

Perphenazine action on vestibular neurons

Abstract The response of single, motion-sensitive neurons in the vestibular nuclei to systemic administration of perphenazine was studied in 18 cats. 14 of the 22 units examined showed depression of their activity. The extent of depression for a given dose varied from one neuron to another; it was independent of specific type of motion sensitivity and whether the animal was in motion or at rest. The other units tested, approximately one-third of the total, showed either an excitatory response, a biphasic depression-excitation or no response at all. These results suggest that the drug effect was not a simple, direct one. Since perphenazine is known to act on ascending systems of the brainstem reticular formation, presumably via adrenergic blockade, the interpretation is offered that response of the vestibular neurons to the drug could have been mediated, in part, through the reticular formation.