Alterations In Firing Rate Research Articles

Lipopolysaccharide effects on neuronal activity in rat basal forebrain and hypothalamus during sleep and waking.

Peripheral administration of lipopolysaccharide (LPS) is associated with alterations in sleep and the electroencephalogram. To evaluate potential neuronal mechanisms for the somnogenic effects of LPS administration, we used unanesthetized rats to survey the firing patterns of neurons in various regions of rat basal forebrain (BF) and hypothalamus during spontaneous sleep and waking and during the epochs of sleep and waking that occurred after the intraperitoneal administration of LPS. In the brain regions studied, LPS administration was associated with altered firing rates in 39% of the neurons examined. A larger proportion of LPS-responsive units showed vigilance-related alterations in firing rates compared with nonresponsive units. Approximately equal proportions of LPS-responsive neurons showed increased and decreased firing rates after LPS administration, with some units in the lateral preoptic area of the hypothalamus showing particularly robust increases. These findings are consistent with other studies showing vigilance-related changes in neuronal activity in various regions of BF and hypothalamus and further demonstrate that peripheral LPS administration alters neuronal firing rates in these structures during both sleep and waking.

Neuronal spike activity in the nucleus accumbens of behaving rats during ethanol self-administration

Many lines of evidence support the importance of the nucleus accumbens (NAC) for ethanol-reinforced behavior. The nature of the neuronal activity that occurs in this region during ethanol self-administration is not known. We recorded from ensembles of single-units primarily located within the shell of the NAC during operant responding for oral ethanol solutions by well-trained rats. Of 90 units recorded from seven sessions from seven rats, 41 (46%) did not exhibit significant changes in relation to the experimental events. Of the 49 units (54%) that did exhibit significant phasic changes, alterations in firing rate occurred in relation to the following experimental events: operant response (63%), tone stimulus (20%), and ethanol delivery (63%). In addition, changes in spike activity during the intervals between the three experimental events were noted in 33% of the units. Most units (55% of responsive units) responded to multiple experimental events. Thus different but overlapping populations of neurons in the NAC represent each event that occurs along the temporal dimension of a single trial performed to obtain ethanol reward. The data suggest that the NAC plays a crucial role in linking together conditioned and unconditioned internal and external stimuli with motor plans to allow for ethanol-seeking behavior to occur.

Medullary raphe neurones and baroreceptor modulation of the respiratory motor pattern in the cat.

1. Perturbations of arterial blood pressure change medullary raphe neurone activity and the respiratory motor pattern. This study sought evidence for actions of baroresponsive raphe neurones on the medullary respiratory network. 2. Blood pressure was perturbed by intravenous injection of an alpha1-adrenergic receptor agonist, unilateral pressure changes in the carotid sinus, or occlusion of the descending aorta in thirty-six Dial-urethane-anaesthetized, vagotomized, paralysed, artificially ventilated cats. Neurones were monitored with microelectrode arrays in two or three of the following domains: nucleus raphe obscurus-nucleus raphe pallidus, nucleus raphe magnus, and rostral and caudal ventrolateral medulla. Data were analysed with cycle-triggered histograms, peristimulus time and cumulative sum histograms, cross-correlograms and spike-triggered averages of efferent phrenic nerve activity. 3. Prolongation of the expiratory phase and decreased peak integrated phrenic amplitude were most frequently observed. Of 707 neurones studied, 310 had altered firing rates during stimulation; changes in opposite directions were monitored simultaneously in fifty-six of eighty-seven data sets with at least two baroresponsive neurones. 4. Short time scale correlations were detected between neurones in 347 of 3388 pairs. Seventeen pairs of baroresponsive raphe neurones exhibited significant offset correlogram features indicative of paucisynaptic interactions. In correlated raphe-ventrolateral medullary neurone pairs with at least one baroresponsive neurone, six of seven ventrolateral medullary decrementing expiratory (E-Decr) neurones increased their firing rate during baroreceptor stimulation. Thirteen of fifteen ventrolateral medullary inspiratory neurones correlated with raphe cells decreased their firing rate during baroreceptor stimulation. 5. The results support the hypothesis that raphe neuronal assemblies transform and transmit information from baroreceptors to neurones in the ventral respiratory group. The inferred actions both limit and promote responses to sensory perturbations and match predictions from simulations of the respiratory network.

Inhibition of firing rate and changes in the firing pattern of nigral dopamine neurons by gamma-hydroxybutyric acid (GHBA) are specifically induced by activation of GABA(B) receptors.

Previous studies have shown that administration of gamma-hydroxybutyric acid (GHBA) or the GABA(B) receptor agonist baclofen are associated with a decrease in firing rate, a regularisation of firing pattern and a decrease in burst activity of midbrain dopamine (DA) neurons in the substantia nigra (SN). In the present study we compared the ability of the novel GABA(B) receptor antagonist SCH 50911 and the selective antagonist of GHBA binding sites, NCS-382, to antagonise the effects of baclofen or GHBA, respectively, on the neuronal activity of DA neurons in anaesthetised rats. SCH 50911 (75 mg/kg, i.v.) was found to antagonise the decrease in firing rate, the regularisation of firing rhythm and the decrease of burst activity in DA cells, induced by baclofen (1-32 mg/kg, i.v.) or GHBA (12.5-1600 mg/kg, i.v.). NCS-382 (100 mg/kg, i.v.) did not affect the baclofen-induced changes in neuronal activity. Neither was the drug able to influence the GHBA-induced alterations in firing rate or in burst activity, although NCS-382 to some extent antagonised the regularisation of the firing pattern observed following low doses of GHBA (< or =100 mg/kg). The results of the present study give further support for the notion that the GHBA-induced changes in neuronal activity of nigral dopamine neurons are mediated by stimulation of GABA(B) receptors.

Presynaptic 5-HT3 receptors evoke an excitatory response in dorsal vagal preganglionic neurones in anaesthetized rats.

1. Recordings were made from a total of sixty-four vagal preganglionic neurones in the dorsal vagal motor nucleus (DVMN) of pentobarbitone sodium anaesthetized rats. The effects of ionophoretic administration of Mg2+ and Cd2+, inhibitors of neurotransmitter release, and the selective NMDA and non-NMDA receptor antagonists (+/-)-2-amino-5-phosphono-pentanoic acid (AP5) and 6,7-dinitroquinoxaline-2,3-dione (DNQX) on the excitatory actions of the 5-HT3 receptor agonist 1-phenylbiguanide (PBG) were studied. 2. In extracellular recording experiments, PBG (0-40 nA) increased the firing rate of thirty-five of the thirty-nine neurones tested. The PBG-evoked excitation was attenuated by application of Mg2+ (1-10 nA) in sixteen of seventeen neurones or Cd2+ (2-10 nA) in seven of eight neurones tested. At these low ejection currents neither Mg2+ nor Cd2+ altered baseline firing rates and Mg2+ had no effect on the excitations evoked by DL-homocysteic acid (n = 4), NMDA (n = 4) or (AMPA; n = 2). 3. Ionophoresis of AP5 (2-10 nA), at currents which selectively inhibited NMDA-evoked excitations, attenuated PBG-evoked excitations in all eight neurones tested. DNQX (5-20 nA), at currents which selectively inhibited AMPA-evoked excitations, also attenuated PBG-evoked excitations (n = 3). 4. Intracellular activity was recorded in nine DVMN neurones. In six neurones ionophoretic application of PBG (10-200 nA) depolarized the membrane and increased firing rate whilst in the other three neurones, PBG had no effect on membrane potential though it increased synaptic noise (n = 3) and firing rate (n = 2). In all six neurones tested, ionophoresis of Mg2+ (10-120 nA) attenuated the PBG-evoked increases in synaptic noise and firing rate. 5. In conclusion, the data are consistent with the hypothesis that 5-HT3 receptor agonists activate DVMN neurones partly by acting on receptors located at sites presynaptic to the neurones. Activation of these receptors appears to facilitate release of glutamate, which, in turn, acts on postsynaptic NMDA and non-NMDA receptors to activate the neurones.

Thyrotropin-releasing hormone: effects on identified neurons of the dorsal vagal complex

Previous reports have demonstrated that intraventricular administration of thyrotropin-releasing hormone (TRH) markedly elevates parasympathetic efferent activity. The following study determined if this response could be attributed to an effect of TRH on the neurons in the dorsal motor nucleus of the vagus (DMN) and/or the nucleus tractus solitarius (NTS), the nuclei that comprise the dorsal vagal complex (DVC). Individual DMN or NTS units were identified electrophysiologically by using stimulating electrodes placed on the cervical vagus. Alterations in firing rate of identified cells in response to pressure injection of TRH (10–40 fmol in 10–40 pl) or equal volumes of artificial cerebrospinal fluid (ACSF) were monitored. Of the DMN cells that were responsive to TRH, all were excited, whereas all responsive NTS cells were inhibited by this peptide. TRH was characterized as potent and had long-lasting effects on cells in DMN and NTS. The action of TRH on both nuclei in the dorsal vagal complex may explain the powerful effects of this peptide on vagally mediated functions.

Dose effects of morphine on the spontaneous unit activity recorded from the thalamus, hypothalamus, septum, hippocampus, reticular formation, central gray, and caudate nucleus.

Spontaneous activity was recorded from 652 units in 8 subcortical structures of unanesthetized rats. Recordings were obtained in central gray, mesencephalic reticular formation, parafasciculus thalami, caudate nucleus, anterior and ventromedial hypothalamus, lateral septum, and dorsal hippocampus. Eighty recordings were obtained from untreated animals and 80 from saline-injected controls, none of which showed any significant changes of unit activity during the 4- 5-hr observation period. The effect of morphine, given in 5 incremental doses from 0.5 to 30.0 mg/kg ip, was followed in 492 units. Morphine enhanced or depressed spontaneous discharge rates, or caused biphasic effects, ie enhancement alternating with depression and vice versa. Naloxone induced increase in firing after either effect of morphine, or reduced spontaneous activity after morphine-induced increases. However, when morphine reduced neuronal discharges, naloxone never caused further depression. In 86 units, morphine at any dosage failed to alter neuronal activity, but in 54 of these units naloxone nevertheless induced alterations in firing rates. The pattern of responses to morphine differed between all 8 brain regions examined and was characteristic for each individual structure. This is the first systematic study describing the dose-response characteristics of morphine in 8 brain sites recorded simultaneously. Furthermore, it utilized freely behaving animals without the interference of anesthetics, which are themselves known to interact with opiates. The variety of response patterns seen supports the neuropharmacological evidence for multiple opiate receptors or multiple sites of opiate action.

Antagonism of ethanol's central stimulation by catecholamine receptor agonists.

The effect of ethanol (2 g/kg) on brain catecholamine neurons in the rat as well as its interaction with catecholamine receptor agonists was studied utilizing single unit recording techniques. Identified dopamine (DA) neurons of the zona compacta, substantia nigra as well as noradrenaline (NA) neurons of the locus coeruleus showed no alterations in firing rate at ethanol administration. Also the function of their presynaptic DA and NA receptors, respectively, appeared normal judging from the unaltered inhibitory response to systemically or microiontophoretically applied receptor agonists, apomorphine and clonidine, respectively, when applied in small doses. In contrast, the catecholamine releasing agent amphetamine caused inhibition of firing of the central catecholamine neurons in the same anesthetized preparation. The rate of tryosine hydroxylation in vivo in central DA and NA neurons measured as the amount of Dopa accumulated in various brain regions following inhibition of aromatic l-amino acid decarboxylase by NSD 1015, 150 md/kg i.p., was significantly increased by ethanol in anesthetized rats. Consequently, the present data do not support the hypothesis derived largely from behavioural evidence that ethanol causes inactivation of central DA and NA neurons. The antagonism by catecholamine receptor agonists, apomorphine and clonidine of ethanol's behaviourally stimulant action may thus be of unspecific character. The results indicate that alterations in tyrosine hydroxylase activity, when measured as Dopa formation after decarboxylase inhibition, can occur without concomitantly altered impulse activity in central DA or NA neurons. At present the action of ethanol on brain DA and NA neurons remains unclear and necessitates further studies.

Spontaneous and osmotically-stimulated activity in slices of rat hypothalamus

HATTON, G. I., W. E. ARMSTRONG AND W. A. GREGORY. Spontaneous and osmotically stimulated activity in slices of rat hypothalamus. BRAIN RES. BULL. 3(5) 497–508, 1978.—Single unit activity was recorded from 400–500 μm thick slices of rat hypothalamus, using either NaCl- or horseradish peroxidase-filled glass micropipettes. Spontaneous activity was present in the following hypothalamic loci: anterior hypothalamic-preoptic area, nucleus circularis, nucleus of the diagonal band of Broca, paraventricular accessory nucleus, paraventricular nucleus (all portions), periventricular regions of the anterior hypothalamus, and the suprachiasmatic nucleus. The supraoptic nucleus was the only major cell group studied to exhibit no spontaneous activity. Cells of the paraventricular and circularis nuclei were spontaneously active, displayed firing rates and patterns of activity similar to those recorded in vivo for magnocellular elements of the hypothalamus, and in some cases responded to increases in the osmolality of the bathing medium with altered firing rates and/or patterns of activity. Many cells in these preparations were characterized by phasic, bursting patterns of activity. Slow, irregular and regular, continuous activity was also frequently observed, as is typical in vivo. Median firing rates were in the range of 4–6 spikes/sec, somewhat faster than the rates usually reported for anesthetized in vivo preparations. These rates are more similar to those observed in unanesthetized monkeys or rats with diencephalic islands. Extracellular HRP marking provided a high degree of localization for many of the recorded cells. These results indicate that the hypothalamic slice preparation is useful for studies in which it is desirable to eliminate extrahypothalamic connections and in which it is necessary to exercise a fine degree of control over the extracellular environment of the cells.

Slow and Rapid Response to CW and Pulsed Microwave Radiation by IndividualAplysisPacemakers

Specific absorption rates (SARs) of microwave energy that altered firing rates were determined for individual pacemaker neurons in the abdominal ganglion of Aplysia californica. A stripline apparatus provided both for artifact-free recording of transmembrane potentials and for precise determination of the rate of absorption of microwave energy. Exposure for two to three minutes at an SAR of only a few mW/g was capable of changing the firing rate of some pacemakers. Two types of responses were observed. The response that was seen in all neurons developed slowly, reaching a steady state in one to three minutes. The other response was seen in a few neurons and occurred within five seconds from the onset of irradiation. Similar responses were obtained for two microwave frequencies, 1.5 and 2.45 GHz. Pulsed radiation induced rapid changes of firing rate more readily than did CW radiation at the same SAR. A convective heating scheme was used to study the effects of temperature changes on the pacemakers' firing rates. Since all of the responses are not readily explained by general heating of the preparation, alternate mechanisms are suggested for the observed effects.

Activity of osmosensitive neurons: Plasma osmotic pressure thresholds

Rats were placed on a 23.5 hr water deprivation schedule. After 5 days on this regimen, firing rates of supraoptic (NSO) and other anterior hypothalamic neurons had significantly increased. Some water deprived rats received a slow intragastric water infusion during recording. Only NSO neurons decreased in firing rate during plasma osmotic pressure decreases. The change in activity occurred when P osm had decreased 2–3%. Following the water load, some rats were injected subcutaneously with a 16% NaCl solution. When P osm increased 2–3% following the injection, firing rates of only NSO neurons increased. Following a painful stimulus (a potent ADH releaser) the firing rate of osmosensitive neurons increased. It was concluded that 2–3% changes in P osm are thresholds for alteration in firing rates of NSO neurons. These thresholds correspond closely to those that elicit the release of vasopressin.

Simple spike firing patterns of cat cerebellar purkinje cells in sleep and waking

1. 1. Previous studies of neuronal activity during sleep have indicated that the pattern of firing of neurons was altered as a function of behavioral state (waking, synchronized sleep and desynchronized sleep). Although not evaluated quantitatively, this change in pattern has been assumed to be independent of changes in firing rate and has formed the basis for postulates of physiological mechanism (such as disinhibition) acting differentially in sleep. In a population of identifiable units, we have examined quantitatively the relationship between firing pattern (as measured by interspike interval histograms and by auto-correlation techniques) and firing rate to see if alterations in firing rate could explain differences in firing pattern observed during behavioral state changes. 2. 2. Simple spikes of 39 Purkinje cells in the cerebellar vermis were recorded by extracellular micro-electrodes during natural sleep and waking in unrestrained, unanesthetized cats. 3. 3. An analysis of covariance demonstrated that characteristics of the form of interspike interval histograms (variance, third moment, fourth moment, percentage of intervals at the mode) were a function of the firing rate of the unit. All units firing with the same mean interspike interval duration tended to have the same histogram form; behavioral state was not an important determinant of histogram form except insofar as the unit firing rate was altered. 4. 4. Auto-correlation analysis demonstrated a tendency toward rhythmic firing with period duration near the modal interval. A high degree of rhythmicity was associated with a high firing rate, and a low degree of rhythmicity was associated with a low firing rate, suggesting that this aspect of firing pattern, like that of histogram characteristics, was also a function of firing rate. 5. 5. These findings indicate that, for simple spikes of cerebellar Purkinje cells, changes in firing rate account for differences in firing patterns observed with behavioral state changes.

Multimodal sensory activation of cells in the magnocellular medial geniculate nucleus

The effects of sound, caloric, tactile, nociceptive, photic, and vestibular stimulation upon 200 extracellularly recorded units of the cat's magnocellular medial geniculate nucleus were studied. Both frequency of firing and interspike interval distribution analysis were used to evaluate changes in the patterns of cellular activity. A prominent short-latency crossed pathway from the vestibular nuclei to the magnocellular nucleus was demonstrated. An ipsilateral projection of longer latency was also found. Repetitive vestibular stimulation, both ipsilateral and contralateral to the recording microelectrode altered firing rates and patterns of interspike intervals in a large number of units in the magnocellular nucleus, many of which were not discharged by single pulse vestibular nucleus stimulation. A multisensory input to the nucleus was shown. Fifteen of the 200 cells studied showed increases in their firing rates with each of four types of sensory stimulation. Not only were rates of unit discharge modified, but there were differential changes in the interspike interval histograms with each modality.