Impulse activity of neurons in the nucleus pontis oralis in cats during sleep--wakefulness cycle

The nucleus pontis oralis contains several populations of neurons showing distinct sleep-waking discharge patterns. PS-on, PS-off cells, and neurons that discharged in association with phasic movements during paradoxical sleep and/or waking, were found. The findings suggest that different populations of the nucleus pontis oralis neurons take a distinct part in paradoxical sleep control.     

Jejunal administration of linoleic acid increases activity of neurons in the paraventricular nucleus of the hypothalamus

The present experiment examined whether neurons located in the paraventricular nucleus of the hypothalamus (PVN) respond to intestinal infusions of long-chain fatty acids. Single-unit recordings were made of neurons located in and adjacent to the PVN during jejunal administration of linoleic acid. Jejunal administration of linoleic acid increased single-unit activity of neurons located in the PVN but did not affect activity of neurons located in adjacent tissue outside the PVN. The largest increases in neuronal activity were observed in the anterior PVN (0.9-1.3 mm posterior to bregma) compared with the posterior PVN (1.8-2.1 mm posterior to bregma). Jejunal administration of saline failed to affect activity of neurons located either inside or outside the PVN. When the same neurons were subsequently tested for their response to intravenous administration of 2 microg/kg of CCK-8, excitatory responses were more frequently observed than inhibitory responses, but both types of responses were observed regardless of whether neurons were located inside or outside the PVN. In addition, there was no strong correlation between the magnitude of the neuronal response evoked by jejunal administration of linoleic acid compared with intravenous CCK-8. These data suggest that neurons located in the anterior PVN may play a role in the mediation of suppression of food intake produced by intestinal administration of lipids.     

Dynamics of neuronal activity in the posterior hypothalamus during alternating phases of the sleep-wake cycle

The dynamics of neuronal activity in the posterior hypothalamus in different phases of the sleep-wake cycle were investigated during experiments on free-ranging cats. The highest frequency discharges were found to occur in 89.3% of neurons belonging to this region during the stages of active wakefulness and emotionally influenced paradoxical sleep. These neurons become less active during restful wakefulness and the unemotional stage of paradoxical sleep; this reduced activity can be most clearly observed in the context of slow-wave sleep. It was found that 7.1% of test neurons discharged at the highest rate during the stage of active wakefulness. They did not achieve an activity level characteristic of active wakefulness during the period of paradoxical sleep, although activity level was higher than during other states. Only 3.6% of neurons followed the opposite pattern, with discharges succeeding more frequently in slow-wave sleep and activity reduced to an equal degree during wakefulness and paradoxical sleep. The neurophysiological mechanisms governing the sleep-wake cycle and how the posterior hypothalamus contributes to these mechanisms are discussed.I. S. Beritashvili Institute of Physiology, Academy of Sciences of Georgian SSR, Tbilisi. Translated from Neirofiziologiya, Vol. 20, No. 2, pp. 160–167, March–April, 1988.     

Medullary taste responses are modulated by the bed nucleus of the stria terminalis

Previous studies have shown a modulatory influence of limbic forebrain areas, such as the central nucleus of the amygdala and lateral hypothalamus, on the activity of taste-responsive cells in the nucleus of the solitary tract (NST). The bed nucleus of the stria terminalis (BST), which receives gustatory afferent information, also sends descending axons to the NST. The present studies were designed to investigate the role of the BST in the modulation of NST gustatory activity. Extracellular action potentials were recorded from 101 taste-responsive cells in the NST of urethane-anesthetized hamsters and analyzed for a change in excitability following bilateral electrical stimulation of the BST. The response of NST taste cells to stimulation of the BST was predominately inhibitory. Orthodromic inhibitory responses were observed in 29 of 101 (28.7%) NST taste-responsive cells, with four cells inhibited bilaterally. An increase in excitability was observed in seven of the 101 (6.9%) NST taste cells. Of the 34 cells showing these responses, 25 were modulated by the ipsilateral BST and 15 by the contralateral; four were inhibited bilaterally and two inhibited ipsilaterally and excited contralaterally. The duration of inhibitory responses (mean = 177.9 ms) was significantly longer than that of excitatory responses (35.4 ms). Application of subthreshold electrical stimulation to the BST during taste trials inhibited or excited the taste responses of every BST-responsive NST cell tested with this protocol. NST neurons that were most responsive to sucrose, NaCl, citric acid or quinine hydrochloride were all affected by BST stimulation, although citric acid-best cells were significantly more often modulated and NaCl-best less often modulated than expected by chance. These results combine with excitatory and inhibitory modulation of NST neurons by the insular cortex, lateral hypothalamus and central nucleus of the amygdala to demonstrate extensive centrifugal modulation of brainstem gustatory neurons.     

Nucleic acid and protein content of cells of the raphe nuclei of the rat brain when the animals are deprived of the paradoxical sleep phase

A 24 hours paradoxical sleep deprivation (PSD) with rats resulted in lowering the RNA content in neurons and gliocytes of n. raphé dorsalis by 31 and 18%, resp.; the protein content remaining unchanged. A 48 hours PSD reduced RNA and protein contents in neurons by 31%; in gliocytes both these substances being on the control level. In the neurons of n. raphé pontis, by the end of the 1st day of PSD the contents of both RNA and protein were seen reduced by 16 and 28%, resp.; however, by the end of the 2nd day their levels well compared with those in the control rats. There was a phase oscillation of protein content in gliocytes: from - 19%, on the first day of PSD, to +19%, on the 2nd day. There is a great resemblance in response to PSD between the adrenergic nucleus - locus coeruleus - and n. raphé pontis, whereas their responses differ from that of the serotoninergic n. raphé dorsalis.     

Responses of neurons of different hypothalamic structures to stimulation of tooth pulp and Aß afferents in the cat sciatic nerve

The response of neurons of different hypothalamic structures to stimulation of painful tooth pulp afferents and painless sciatic nerve Aß afferents was investigated during acute experiments on cats. It was found that 80.7%, 81.5%, and 71.4% of neurons of the posterior, tuberal, and anterior hypothalamus respectively, responded to stimulation of the tooth pulp. Shortest latency of response was recorded in the posterolateral hypothalamus. Latency of response was shorter in the lateral than in the medial structures throughout the hypothalamus. A distinct prevalence of excitatory response was found in neurons of the posterior area and an almost equal proportion of excitatory and inhibitory response in neurons of the tuberal and anterior hypothalamus. A high degree of convergence between noxious and nonnoxious somatic afferents were discovered in hypothalamic neurons: 85.8% of those studied responded to stimulation of the sciatic nerve Aß afferents. The comparable unidirectional response pattern of hypothalamic neurons to stimulation of tooth pump painful afferents and painless sciatic nerve Aß fibers point to the nonspecific nature of the response observed in the mainstream population of multisensory hypothalamic neurons. A small population of unimodal nociceptive neurons (14.2%) was found in the hypothalamus. Nociceptive responses of anterior hypothalamic neurons were distinguished by their long refractory phase, lasting 200–500 msec, and their low rate of reproduction during rhythmic stimulation of tooth pulp (1.5–2 Hz). Neuronal organization of the nociceptive hypothalamic afferent system is discussed together with the role of convergent and specific "nociceptive" neurons in the shaping of thalamic regulatory functions.L. A. Orbeli Institute of Physiology, Academy of Sciences of the Armenian SSR, Erevan. Translated from Neirofiziologiya, Vol. 18, No. 2, pp. 171–180, March–April, 1986.     

Unit responses in the anterior and posterior hypothalamus to stimulation of the splanchnic and sciatic nerves and to photic stimulation

By extracellular recording of spike discharges the sensory properties of neurons of the anterior and posterior regions of the cat hypothalamus were studied during stimulation of the splanchnic and sciatic nerves and during photic stimulation. Hypothalamic neurons were shown to be characterized by wide convergence of heterosensory excitation: 68% of spontaneously active hypothalamic neurons responded to somatovisceral and photic stimulation. Some posterior hypothalamic neurons responded to somatovisceral stimulation but not to photic stimulation. Neurons responding only to photic stimulation were found in the anterior hypothalamus; no neurons responding only to visceral stimulation were found in the hypothalamus. Total convergence of somatic and visceral afferentation of neurons of the posterior and anterior hypothalamus was observed. Mostly responses of phasic type were obtained to stimulation of all modalities. The study of the quantitative ratio between responses of excitatory and inhibitory types showed that the former predominate. The principles governing the functional organization of hypothalamic afferent systems are discussed.Academician L. A. Orbeli Institute of Physiology, Academy of Sciences of the Armenian SSR, Erevan. Translated from Neirofiziologiya, Vol. 8, No. 3, pp. 276–282, May–June, 1976.     

The role of the posterior hypothalamus in the regulation of paradoxical sleep

Posterior hypothalamus was found to take part in the inhibitory control of the paradoxical sleep executive mechanisms responsible for the ECoG desynchronisation and phasic events. Functional activity of the posterior hypothalamus seems to be at its lowest during the paradoxical sleep stage as characterised by phasic events and the ECoG desynchronisation, and increases during the stage with alpha-like activity in the ECoG and absence of phasic events, the latter having, probably, a "sentinel" function.     

Electrophysiological analysis of corticofugal influences on preoptic neurons

Evoked potential (EPs) and responses of the medial (MPO) and lateral (LPO) preoptic region (RPO) and adjacent structures of the hypothalamus to stimulation of the prefrontal (area 8) and cingulate (area 24) cortex, piriform lobe (periamygdaloid cortex), and hippocampus (area CA3) were investigated in acute experiments on cats under ketamine anesthesia. The most pronounced EPs were observed in the RPO after stimulating the piriform and cingulate cortex. A close relation was found between neuronal responses and EP components. The majority of neurons responding to stimulation of various cortical structures were localized in the LPO, where primarily excitatory responses dominate. The MPO contained somewhat fewer neurons responding to cortical stimulation, and the dominant response here was primarily inhibitory. The ratio of inhibitory and excitatory responses in the LPO was 0.6:1 and in the MPO 5.8:1. Primarily in-inhibitory responses dominated also in the LPO zone adjacent to the bed nucleus stria terminalis (BST) and primarily excitatory in the region surrounding the supraoptic nucleus (SO) (respective ratios 4.9:1 and 0.7:1). The RPO is a broad convergence zone, where 3/4 of the neurons responded to stimuli of two and more cortical regions.A. M. Gorky Medical Institute, Ukrainian Minstry of Health, Donetsk. Translated from Neirofiziologiya, Vol. 23, No. 6, pp. 709–719, November–December, 1991.     

Preoptic area sleep-regulating mechanisms

Evidence is summarized for the existence of a sleep-regulating mechanism within the preoptic area of the hypothalamus, including the results of lesion, stimulation, and neuronal recording studies. Recent findings employing the c-fos protein immunohistochemical method, have localized putative sleep-regulatory neurons to the ventrolateral preoptic area (vlPOA) and the median preoptic nucleus (MnPn). Electrophysiological studies have confirmed the presence of neurons with sleep-related discharge in the vlPOA. Neurons in the vlPOA that exhibit c-fos protein immunoreactivity during sleep contain the inhibitory neuromodulators galanin and gamma-aminobutyric acid (GABA). These neurons also project to monoaminergic arousal systems, particularly the histaminergic cell groups in the posterior hypothalamus. POA neurons can be hypothesized to provide sleep-related inhibitory control over multiple arousal systems in the forebrain and brainstem.     

Further evidence for a possible excitatory serotonergic synapse on raphe neurons of pons and lower midbrain

Iontophoretic techniques were employed to investigate the response of neurons in the nucleus raphe pontis and median raphe nucleus to 5HT. Neurons were identified by response to stimulation of nucleus paragigantocellularis lateralis (NPL) as driven (D), inhibited (I) or non-responsive (NR) cells. Of 35 D cells tested, 33 were excited by 5HT and 2 inhibited. Of 10 I cells tested, 7 were inhibited by 5HT and 3 excited. Of 56 NR cells tested, 5HT excited 30, inhibited 23 and produced no response for 3. Combining this and previous work, 100 D cells have been tested of which 97 were excited by 5HT. This 97% excitatory response of D cells to 5HT provides a strong suggestion that the NPL-to-raphe projection represents an excitatory serotonergic pathway in the central nervous system.     

Basal ganglia influences on the cerebellum of the cat

The changes in firing rate of intracerebellar nuclear neurons following electrical stimulation of the contralateral basal ganglia were investigated in adult cats, in which antidromic activation of cortico-pontine and/or cortico-olivar fibers arising in the area 6 had been excluded by chronic ablation of the motor cortex. Activation of putamen and caudate nucleus induced discharge changes in a low percentage (below 12.5%) of both medial and lateral cerebellar nuclei neurons, while stimulation of globus pallidus and especially of entopeduncular nucleus modified the spontaneous discharge of a greater percent of cells (up to 29%), mainly in the most lateral cerebellar portions. The basal ganglia-induced effects were abolished upon section of the brachium pontis but not of the restiform body. Latency values of the responses, which were predominantly excitatory in nature, suggest the involvement of structures interposed between basal ganglia and precerebellar systems. We postulated that impulses issued by the basal ganglia could reach the cerebellum through a pathway that involves the pedunculopontine nucleus and the nucleus reticularis tegmenti pontis.     

Role of hypothalamic adenosinergic systems in regulating states of wakefulness in the rat

Immunohistochemical localization of adenosine deaminase (ADA), marker for the putative neurotransmitter/neuromodulator adenosine, has revealed a population of ADA-positive neurons in the ventrolateral hypothalamus in the rat brain. These posterior neurons possess adenosine uptake sites. We have studied the effects of local injections of adenosinergic drugs on the sleep-wake cycle in the rat. Microinjection of erythro-9-(hydroxy-2, nonyl-3) adenine (EHNA), a specific inhibitor of adenosine deaminase, resulted in a significant decrease in wakefulness (W) and an increase in deep slow wave sleep (SWS, or S2) and paradoxical sleep (SP). On the other hand, microinjections of soluflazine, a nucleoside transport inhibitor, increased W and decreased total sleep. These opposite modifications may reflect opposite variations in the extracellular concentrations of Ado and consequently different responses of A1/A2 adenosine receptors.     

Glucose-sensing neurons of the hypothalamus

Specialized subgroups of hypothalamic neurons exhibit specific excitatory or inhibitory electrical responses to changes in extracellular levels of glucose. Glucose-excited neurons were traditionally assumed to employ a 'beta-cell' glucose-sensing strategy, where glucose elevates cytosolic ATP, which closes KATP channels containing Kir6.2 subunits, causing depolarization and increased excitability. Recent findings indicate that although elements of this canonical model are functional in some hypothalamic cells, this pathway is not universally essential for excitation of glucose-sensing neurons by glucose. Thus glucose-induced excitation of arcuate nucleus neurons was recently reported in mice lacking Kir6.2, and no significant increases in cytosolic ATP levels could be detected in hypothalamic neurons after changes in extracellular glucose. Possible alternative glucose-sensing strategies include electrogenic glucose entry, glucose-induced release of glial lactate, and extracellular glucose receptors. Glucose-induced electrical inhibition is much less understood than excitation, and has been proposed to involve reduction in the depolarizing activity of the Na+/K+ pump, or activation of a hyperpolarizing Cl- current. Investigations of neurotransmitter identities of glucose-sensing neurons are beginning to provide detailed information about their physiological roles. In the mouse lateral hypothalamus, orexin/hypocretin neurons (which promote wakefulness, locomotor activity and foraging) are glucose-inhibited, whereas melanin-concentrating hormone neurons (which promote sleep and energy conservation) are glucose-excited. In the hypothalamic arcuate nucleus, excitatory actions of glucose on anorexigenic POMC neurons in mice have been reported, while the appetite-promoting NPY neurons may be directly inhibited by glucose. These results stress the fundamental importance of hypothalamic glucose-sensing neurons in orchestrating sleep-wake cycles, energy expenditure and feeding behaviour.     

Blood flow and pO2 in the posterior hypothalamus of cats during paradoxical sleep

In chronic experiments on cats it has been found by recording of the brain local blood flow (BLBF) and of oxygen tension (pO2) in the posterior and anterior hypothalamus, that at sleep phases alternation, the changes of these parameters are differently directed: during the paradoxical sleep the level of BLBF and pO2 oscillations frequency increased in the posterior hypothalamus and decreased in the anterior one. During slow-wave sleep opposite relations were observed. Opposite directions of changes of BLBF level and pO2 oscillations frequency in one and the same phase of sleep show that they are of local origin and must be determined by functional-metabolic shifts. In particular, the increase of BLBF level and frequency of pO2 oscillations must reflect a rise of posterior hypothalamus functional-metabolic activity during paradoxical sleep.     

Corticofugal influences on the neurons of different regions of the hypothalamus

Responses of the neurons of the lateral and ventromedial hypothalamic regions (HL andHvm, respectively), as well as of the area of the dorsal hypothalamus (aHd) and the projection region of the medial forelimb bundle (MFB), evoked by stimulation of the proreal cortex (field 8), cingular cortex (field 24), pyriform lobula (periamigdalar cortex), and hippocampus (CA3) were studied in acute experiments on cats under ketamine anesthesia. Distributions of the latent periods of the responses recorded from hypothalamic neurons at stimulation of the above cortical structures were analyzed. The responses were classified into primary excitatory and primary inhibitory. Stimulation of the proreal gyrus evoked four times more excitatory responses than inhibitory responses. With stimulation of the cingular gyrus, the ratio of excitatory/inhibitory responses was 1.5∶1. Stimulation of the pyriform cortex evoked activatory and inhibitory responses with a similar probability. With hippocampal stimulation, inhibitory responses appeared two times more frequently than excitatory reactions. The hypothalamus was found to be a zone of wide convergence: one-half of all responding neurons in theHL andHvm responded to stimulations of two or more tested cortical zones. In 26% of the cells, only excitatory convergence was observed, while in 10% only inhibitory convergence was found; 21% of the cells revealed mixed convergence.     

Convergence of visceral afferent impulses on hypothalamic neurons during vagal and splanchnic nerve stimulation

Responses of posterior and anterior hypothalamic neurons to stimulation of the vagus, splanchnic, and sciatic nerves, and also to photic stimulation were studied by extracellular recording of spike activity in cats anesthetized with chloralose and immobilized with succinylcholine. Most responding neurons of the posterior and anterior hypothalamus did so to stimulation of both vagus and splanchnic nerves. The responses of these polysensory neurons to stimulation of visceral afferents of parasympathetic nerves were identical in sign and mainly excitatory in type. The absence of a reciprocal character of the response to stimulation of "antagonistic" autonomic nerves and the marked polysensory convergence are evidence of the nonspecific "reticular" character of activation of most of the neurons in the posterior and anterior hypothalamus.L. A. Orbeli Institute of Physiology, Academy of Sciences of the Armenian SSR, Erevan. Translated from Neirofiziologiya, Vol. 9, No. 2, pp. 165–170, March–April, 1977.     

Excitatory and inhibitory responses of the ongoing sympathetic discharge in single renal neurons to liminal stimulation of aortic C-fibres in the rabbit

Excitatory and inhibitory responses of sympathetic discharge were recorded in single renal postganglionic neurons of rabbits anaesthetized with urethane and chloralose. The animals were vagotomized and had transected aortic nerves. Responses were elicited by single volleys in the aortic C-fibres. Excitatory responses consisted in short-lasting increase in the rate of ongoing sympathetic discharge and were followed by inhibitory responses. Excitatory effects together with inhibitory responses were seen in 68% of units (19/28). Only excitatory effects appeared in 2 neurons (7.1%) and only inhibitory effects in 7 neurons (25%). In renal neurons exhibiting both effects, the excitatory responses appeared after latency of 172 +/- 8 ms (x +/- S.D.) and had duration of 64 +/- 11 ms. Inhibitory effects had latency o f 257 +/- 10 ms and their duration amounted to 265 +/- 22 ms. In more than half of recordings the excitatory responses were separated from the inhibitory effects by discharge lasting 33 +/- 4 ms. Significant correlations between latencies of excitatory and inhibitory responses and between duration of excitatory and latency of inhibitory responses suggest interaction between both effects. Increase in the number of afferent volleys (1 through 5) evoked relatively small changes in duration of the excitatory effect indicating that temporal facilitation is of minor importance in generating this response. Temporal facilitation was found to play an important role in determining duration of the inhibitory response. Comparison of effects of unilateral and bilateral stimulation of the aortic C-fibres showed larger occlusion of durations of the excitatory than inhibitory responses.     

Possible mechanisms of the anterior limbic cortex influence on the neuron activity of the vago-solitary complex

In ananesthetized cats, neurons of the nucleus of the tractus solitarius (NTS) and the dorsal motor nucleus of the vagus nerve (DMNV) revealed phasic excitatory responses to separate single vagal and cortical stimuli. Stimulation of the anterior limbic cortex combined with vagal stimulation resulted in inhibitory or excitatory modification of the vagal induced responses of the NTS and DMNV neurons. The data obtained suggest that complete inhibitory effects are related to general cortical mechanisms of control of the functional state of the brain stem visceral neurons. Selective inhibition of the vagal induced responses by limbic cortex stimulation is due to particular cortical mechanisms of the visceral sensory transmission control via the NTS neurons.     

Response properties of visual neurons in the turtle nucleus isthmi

The optic tectum holds a central position in the tectofugal pathway of non-mammalian species and is reciprocally connected with the nucleus isthmi. Here, we recorded from individual nucleus isthmi pars parvocellularis (Ipc) neurons in the turtle eye-attached whole-brain preparation in response to a range of computer-generated visual stimuli. Ipc neurons responded to a variety of moving or flashing stimuli as long as those stimuli were small. When mapped with a moving spot, the excitatory receptive field was of circular Gaussian shape with an average half-width of less than 3°. We found no evidence for directional sensitivity. For moving spots of varying sizes, the measured Ipc response-size profile was reproduced by the linear Difference-of-Gaussian model, which is consistent with the superposition of a narrow excitatory center and an inhibitory surround. Intracellular Ipc recordings revealed a strong inhibitory connection from the nucleus isthmi pars magnocellularis (Imc), which has the anatomical feature to provide a broad inhibitory projection. The recorded Ipc response properties, together with the modulatory role of the Ipc in tectal visual processing, suggest that the columns of Ipc axon terminals in turtle optic tectum bias tectal visual responses to small dark changing features in visual scenes.