Spontaneous Multiple Unit Activity Research Articles

The Effects of Fluoxetine on Sensory-Evoked Responses in the Neonatal Rat Barrel Cortex

Inhibition of serotonin uptake disrupts the development of thalamocortical barrel maps in neonatal rodents. Previous studies, using the selective serotonin reuptake inhibitor citalopram, have suggested that this may involve a suppression of the early activity in the developing cortex. Here, we addressed the acute effects of another frequently used serotonin uptake inhibitor, fluoxetine (10–120 mg/kg, intraperitoneally), on the sensory-evoked electrical responses in the neonatal (postnatal days P2-6) rat barrel cortex. We found that the administration of fluoxetine minimally affected the sensory-evoked responses in the rat pups. Two hours after the fluoxetine administration, there was a slight increase in the sensory-evoked potential (SEP) onset latency. There also was a tendency of SEP’s amplitude to decrease, but this was not significant. Fluoxetine also had no significant effect on the multiple unit activity during the SEP and sensory-evoked bursts and neither did it affect the spontaneous multiple unit activity. We suggest that the inhibitory effects of fluoxetine on the activity in the neonatal rat barrel cortex are much weaker, or that they develop over a slower time scale, than those evoked by citalopram, probably reflecting a lower potency of fluoxetine to inhibit the serotonin uptake.

Rhythmic spontaneous activity in the developing avian auditory system

Microelectrode recordings of spontaneous multiple unit activity were made from nucleus magnocellularis (NM) and nucleus laminaris (NL), second- and third-order nuclei in the chick auditory system, between 14 and 19 d of incubation (E14-E19). Spontaneous firing in E14-E18 embryos occurred in synchronous bursts at periodic intervals. A rhythmic pattern of spontaneous firing was also observed in the auditory nerve but not in nonauditory regions of the brain-stem. The mean interburst interval in NM and NL decreased from 4.9 sec at E14-E15 to 2.1 sec at E18. By E19, 2 d prior to hatching, synchronous bursting was replaced by an unpatterned, steady level of firing comparable to the background discharge that is present in NM and NL of hatchling birds. Bursting was not correlated with heart beat or respiration and was not affected by removal of the middle-ear ossicle. Rhythmic bursting could be reset, blocked, or induced by sound stimulation. Cochlea removal or pharmacological blockade of auditory nerve activity with TTX eliminated bursting. These results indicate that the synchrony and rhythmicity of impulse firing reflect normal physiological activity, most likely of cochlear origin. The present findings show that spontaneous activity in the embryonic avian auditory system, like that in the immature mammalian visual pathway (Maffei and Galli-Resta, 1990; Meister et al., 1991), occurs in a synchronously rhythmic pattern. This similarity raises the possibility that such activity may be a general feature of early sensory system development. Patterned spontaneous firing in the chick takes place during a period of embryogenesis when auditory thresholds are high and when it is unlikely that physiological function in ovo is influenced significantly by normally occurring levels of airborne sound. Brainstem auditory neurons undergo substantial changes in structure and innervation during this same period. It is speculated that the temporal pattern of spontaneous discharge may provide cues that contribute to these developmental events.

Age-related change in the multiple unit activity of the rat brain parietal cortex and the effect of centrophenoxine

In this study, spontaneous multiple unit activity (MUA, action potentials derived simultaneously from a number of neurons in a given brain region) was recorded through electrodes chronically implanted in the parietal cerebral cortex of the rats of 1, 3, 6, 9, 12, and 26 months of age (cross-sectional study). Electrophysiological recordings were obtained from unrestrained conscious rats using standard techniques. The results indicated that multiple unit activity was decreased with aging (senescence). Maximum firing rate (MUA counts) was found at the age of 3 months. At 6 months of age, the MUA was decreased by about 30%, while during 6 to 12 months of age the activity seemed to remain unchanged. At 26 months of the age the firing rate was, however, further decreased (about 40%). Centrophenoxine administration led to an increase in MUA in the rats of 12 and 26 months of age. The results, thus, further showed that centrophenoxine, a nootropic drug known for its antiaging effects in experimental animals as well as in humans, also manifested beneficial effects electrophysiologically. The data presented in this work are new and significant, since although age effects on gross electrophysiological signals (EEG, evoked potentials, etc.) are known, the aging changes in cellular level electrophysiological signals (action potentials) have not been generally studied particularly in conscious animals.

Activation of striatal neurons by dexamphetamine is antagonized by degeneration of striatal dopaminergic terminals

Unilateral degeneration of nigrostriatal dopaminergic terminals by the intranigral infusion of 6-OHDA produced a decrease in spontaneous multiple unit activity (MUA) in both the ipsilateral and contralateral striata of freely moving rats. Nigral lesions also attenuated the dexamphetamine-induced increase in MUA in the ipsilateral but not in the contralateral striatum. The magnitude of the attenuation in the ipsilateral striatum was directly proportional to the percent depletion of dopamine. Similarly degeneration of dopaminergic terminals produced by a unilateral application of 6-OHDA into the striatum lowered spontaneous MUA and completely antagonized the dexamphetamine-induced increase in MUA in the dopamine-depleted striatum. Although the spontaneous MUA in striata contralateral to a local 6-OHDA treatment was significantly reduced, the response to dexamphetamine was normal. Both striatal and nigral application of 6-OHDA produced dopamine depletion in the ipsilateral striatum and an increase in striatal dopamine levels on the contralateral side. Striatal application of 6-OHDA did not alter dopamine levels in either the olfactory tubercles, piriform cortex or cingulate cortex. It is concluded that the increase in MUA observed in the striatum following dexamphetamine treatment is critically dependent upon the release of dopamine in the striatum. These results support the concept that dopamine may have an excitatory action on some striatal neurons.

Spontaneous multiple unit activity from the preoptic nucleus and changes in blood pressure in the rainbow trout Salmo gairdneri under acute experimental conditions

1. 1. Multiple unit activity (MUA) from the preoptic nucleus (NPO) blood pressure and heart rate were recorded in 41 anaesthetized and curarized rainbow trout. 2. 2. Mayer waves were frequently observed in blood pressure recordings (83%). 3. 3. Rhythmic MUA from the NPO, recorded in 46% of the experimented trout, occurred preferentially during Mayer waves. 4. 4. The initiation of the period of MUA occurred during low pressure vasomotor tone and large vasomotor pulse pressure inhibited MUA. 5. 5. Sustained decrease in blood pressure induced proportional rise in MUA. 6. 6. These results suggest that cardiovascular inputs influence the electrical activity of neurosecretory cells within the NPO and so may modulate the neurohypophysial hormones secretion.

Responses of striatal neurons to anesthetics and analgesics in freely moving rats

1. 1. The effects of anaesthetics and analgesics on striatal neurons were examined in freely moving rats by recording extracellular action potentials of neurons in the striatum. 2. 2. Spontaneous multiple unit activity was reduced to less than 20% of control firing rates following either pentobarbital 35 mg/kg i.p., halothane 3%, chloral hydrate 400 mg/kg i.p., or urethane 1.5 g/kg i.p. 3. 3. Morphine 15 mg/kg i.p., decreased striatal neuronal firing whereas ketamine, 50 mg/kg i.p., excited striatal neurons. 4. 4. The only analgesic agent tested that did not significantly affect striatal neuronal firing was nitrous oxide (70% N 2O/30% O 2). 5. 5. These findings demonstrate that nitrous oxide is a suitable analgesic which can be used to alleviate stress and pain associated with immobilization procedures without appreciably altering spontaneous striatal discharge rates.

Effects of morphine on spontaneous multiple-unit activity: Possible relation to mechanisms of analgesia and reward

The effects of morphine (15 mg/kg) on multiple-unit activity in the awake rat were investigated at brain sites previously characterized by their ability to support stimulation-produced analgesia (SPA) and intracranial self-stimulation (ICSS). Of the SPA and SPA + ICSS sites, most of which were located in the periaqueductal gray matter, 91% showed increased multiple-unit activity after morphine administration (median increase = 80%). In contrast, only 50% of the ICSS-only sites, most of which were located in the lateral hypothalamus, and only 29% of sites supporting neither behavior showed this effect. All increases in multiple-unit activity were at least partly reversed by naloxone (1 mg/kg). Latencies to their onset and to analgesia measured by the tail-flick method were significantly correlated. A significant negative correlation was found between ICSS current thresholds and increases in multiple-unit activity after morphine at ICSS-only sites. These data lend further support to the suggestion that morphine exerts its analgesic action by activating an endogenous analgesic system and that the periaqueductal gray constitutes an important part of such a system. Furthermore, it is suggested that morphine's excitatory effect at self-stimulation loci may reflect its rewarding properties.

Effects of pain-attenuating brain stimulation and morphine on electrical activity in the raphe nuclei of the awake rat

Evoked potential and multiple unit responses to noxious shock and pinch as well as to innocuous air puffs were recorded in the dorsal raphe, median raphe and raphe magnus nuclei of awake rats. Concurrent measurements of various behavioral responses to noxious stimuli were also made. Electrical stimulation of midbrain central gray and of medial thalamus, as well as systemic administration of morphine, greatly diminished all behavioral and electrophysiological responses to noxious stimuli without reliably affecting responses to air puffs. At the same time that brain stimulation and morphine attenuated nociceptive responses, a significant elevation was seen in the spontaneous multiple unit activity of these brain areas, particularly nucleus raphe magnus. In another group of animals, a comparison was made of the analgesic effectiveness of stimulation sites in the bulbar raphe (including raphe magnus) and sites dorsal or lateral to this region. More consistently potent effects were obtained from the raphe placements. These findings point to the importance of the bulbar raphe in mechanisms of analgesia. It is suggested that brain stem stimulation and morphine administration activate descending controls of raphe origin which selectively inhibit nociceptive elements in the spinal cord.

Morphine and enkephalin: analgesic and epileptic properties.

Systemic and intracerebroventricular administration of analgesic doses of morphine resulted in large increments of spontaneous multiple unit activity in the periaqueductal gray matter of the awake rat. Intracerebroventricular injection of methionine enkephalin gave analgesia in only 8 of 19 rats, but in all 8, and in no others, increased periaqueductal multiple unit firing was also seen. These findings support the view that the periaqueductal gray matter is actively involved in endogenous mechanisms of analgesia. A striking observation was that enkephalin caused electrographic and behavioral epileptic phenomena in most animals. This observation together with other recent findings suggests that endogenous enkephalin may play some role in epileptogenesis.

Involvement of both cholinergic and catecholaminergic pathways in the central action of methylphenidate: A study utilizing lead-exposed rats

The effects of methylphenidate (MPH) and the cholinergic agonists nicotine and oxotremorine were tested on the spontaneous multiple unit activity in the mesencephalic reticular formation of two groups of rats. In control rats i.v. MPH (1 mg/kg), nicotine (0.125 mg/kg), and oxotremorine (0.5 mg/kg) all attenuated the unit activity with latencies of less than 10 min. In another group of rats, exposed to lead acetate since birth, the extent of attenuation of unit activity induced by MPH and nicotine was reduced and the latency of effect was delayed by 45--50 min. The latency of the oxotremorine effect was not changed but the attenuation of unit activity was more pronounced in the lead-treated group. Pretreatment with spiroperidol, to inhibit the aminergic receptors, diminished the inhibitory effect of MPH in the control group but not in the lead-treated group, whereas the attenuating effect of oxotremorine was not affected in either group. These data support our previous evidence that MPH exerts its action in the central nervous system by a cholinergic pathway in addition to published catecholaminergic pathways. Furthermore, the present findings indicate that chronic lead-exposure in rats results in cholinergic hypofunction and supersensitivity at central cholinergic receptor sites. This alteration of central cholinergic function may be partially attributed to the malnutrition observed in the lead-exposed animals.

Effects of local illumination of the hypothalamus on spontaneous and flash‐induced multiunit activity recorded from the gonadotropic hypothalamic areas in quail

Multiple unit activity (MUA) was obtained from gonadotropic areas of the hypothalamus in quail. Pellets of radioluminous paint (RLP) were implanted unilaterally either in the nucleus tuberis or in the n. posterior medialis hypothalami. Control data were obtained from birds receiving nonluminous material (RP). Spontaneous MUA was decreased by 25% in gonadotropic arease in RLP-treated quail. Direct permanent photostimulation of hypothalamic neuronal population was not as effective in decreasing MUA as environmental photostimulation (50%). Activation in firing rates, which was constant in nonphotostimulated intact birds in response to repetitive flash-light stimulations, was completely suppressed after implantation of RLP.

Effect of ACTH and hydrocortisone on multiple unit activity in the forebrain and thalamus in response to reticular stimulation

The spontaneous multiple unit activity (MUA) of various brain areas and their responsivity to mesencephalic reticular formation stimulation were studied in chronically implanted, freely moving, intact and adrenalectomized cats. Electrical stimulation of the mesencephalic reticular formation were performed exclusively during slow-wave sleep when the MUA was low and stable. Hydrocortisone resulted in a general decrease of MUA level in the mesencephalic reticular formation, the medial forebrain bundle at the anterior hypothalamic level, the medial preoptic area, the n. centromedianus and the fornix. The responsiveness of the structures to reticular stimulation was much lower in adrenalectomized than in normal animals and this reactivity was further lowered by hydrocortisone injection. ACTH injections resulted in a decrease of spontaneous activity and responsiveness in the medial preoptic area, both in normal and adrenalectomized animals, whereas a slight increase of MUA responsivity was found in the fornix and the medial forebrain bundle in response to reticular stimulation.