We describe a novel slow oscillation in intracellular recordings from cortical association areas 5 and 7, motor areas 4 and 6, and visual areas 17 and 18 of cats under various anesthetics. The recorded neurons (n = 254) were antidromically and orthodromically identified as corticothalamic or callosal elements receiving projections from appropriate thalamic nuclei as well as from homotopic foci in the contralateral cortex. Two major types of cells were recorded: regular-spiking (mainly slow-adapting, but also fast-adapting) neurons and intrinsically bursting cells. A group of slowly oscillating neurons (n = 21) were intracellularly stained and found to be pyramidal-shaped cells in layers III-VI, with luxuriant basal dendritic arbors. The slow rhythm appeared in 88% of recorded neurons. It consisted of slow depolarizing envelopes (lasting for 0.8-1.5 sec) with superimposed full action potentials or presumed dendritic spikes, followed by long-lasting hyperpolarizations. Such sequences recurred rhythmically at less than 1 Hz, with a prevailing oscillation between 0.3 and 0.4 Hz in 67% of urethane-anesthetized animals. While in most neurons (approximately 70%) the repetitive spikes superimposed on the slow depolarization were completely blocked by slight DC hyperpolarization, 30% of cells were found to display relatively small (3-12 mV), rapid, all-or-none potentials after obliteration of full action potentials. These fast spikes were suppressed in an all-or-none fashion at Vm more negative than -90 mV. The depolarizing envelope of the slow rhythm was reduced or suppressed at a Vm of -90 to -100 mV and its duration was greatly reduced by administration of the NMDA blocker ketamine. In keeping with this action, most (56%) neurons recorded in animals under ketamine and nitrous oxide or ketamine and xylazine anesthesia displayed the slow oscillation at higher frequencies (0.6-1 Hz) than under urethane anesthesia (0.3-0.4 Hz). In 18% of the oscillating cells, the slow rhythm mainly consisted of repetitive (15-30 Hz), relatively short-lasting (15-25 msec) IPSPs that could be revealed by bringing the Vm at more positive values than -70 mV. The long-lasting (approximately 1 sec) hyperpolarizing phase of the slow oscillation was best observed at the resting Vm and was reduced at about -100 mV. Simultaneous recording of another cell across the membrane demonstrated synchronous inhibitory periods in both neurons. Intracellular diffusion of Cl- or Cs+ reduced the amplitude and/or duration of cyclic long-lasting hyperpolaryzations.(ABSTRACT TRUNCATED AT 400 WORDS)

https://www.jneurosci.org/content/jneuro/13/8/3252.full.pdf

A novel slow (< 1 Hz) oscillation of neocortical neurons in vivo: depolarizing and hyperpolarizing components

The specificity of the ‘nonspecific’ midline and intralaminar thalamic nuclei

The cell membrane Na,K-ATPase is a member of the P-type family of active cation transport proteins. Recently the molecular structure of the related sarcoplasmic reticulum Ca-ATPase in an E1 conformation has been determined at 2.6 A resolution. Furthermore, theoretical models of the Ca-ATPase in E2 conformations are available. As a result of these developments, these structural data have allowed construction of homology models that address the central questions of mechanism of active cation transport by all P-type cation pumps. This review relates recent evidence on functional sites of Na,K-ATPase for the substrate (ATP), the essential cofactor (Mg(2+) ions), and the transported cations (Na(+) and K(+)) to the molecular structure. The essential elements of the Ca-ATPase structure, including 10 transmembrane helices and well-defined N, P, and A cytoplasmic domains, are common to all PII-type pumps such as Na,K-ATPase and H,K-ATPases. However, for Na,K-ATPase and H,K-ATPase, which consist of both alpha- and beta-subunits, there may be some detailed differences in regions of subunit interactions. Mutagenesis, proteolytic cleavage, and transition metal-catalyzed oxidative cleavages are providing much evidence about residues involved in binding of Na(+), K(+), ATP, and Mg(2+) ions and changes accompanying E1-E2 or E1-P-E2-P conformational transitions. We discuss this evidence in relation to N, P, and A cytoplasmic domain interactions, and long-range interactions between the active site and the Na(+) and K(+) sites in the transmembrane segments, for the different steps of the catalytic cycle.

Structure and mechanism of Na,K-ATPase: functional sites and their interactions

Restricted cortical termination fields of the midline and intralaminar thalamic nuclei in the rat.

The lower limb flexion reflex in humans.

Previous studies have shown that muscle exercise and low frequency transcutaneous nerve stimulation (TNS) give rise to an analgesic effect in humans and animals. Endorphin has been proposed to mediate this analgesia. In this investigation, the effect of muscle exercise and low frequency TNS, on dental pain thresholds was studied and the possible involvement of endorphinergic mechanisms was investigated using naloxone as an antagonist. Dental pain thresholds were measured in 11 volunteers following leg or arm exercise and after low frequency TNS of the hands or face. After exercise (20 min) or stimulation (30 min) either 0.8 mg naloxone (2 ml) or saline (2 ml) was injected i.v. in a double-blind fashion. Pain thresholds were measured repetitively before and after exercise or stimulation. Both leg and arm exercise increased pain threshold. Stimulation of the hands also increased pain threshold, but less than arm exercise. A marked increase in pain threshold was seen after face stimulation. These changes in pain threshold were unaffected following injections of either naloxone or saline, except for an early and short-lasting reduction when naloxone was injected following arm exercise. The increases in pain threshold following muscle exercise and after low frequency TNS, showed similarities suggesting that a common mechanism might be involved. The pain threshold increase after arm exercise could only be partially mediated by endorphinergic mechanisms.

Effects of naloxone on dental pain threshold following muscle exercise and low frequency transcutaneous nerve stimulation: a comparative study in man.

Field potentials and single cell activity evoked by tooth pulp (TP) stimulation were studied in the ventrobasal (VB) complex of the cat. The experiments were performed using a conditioning-test paradigm. Evoked cell activity or field potentials following TP stimulation was used as a test. Conditioning stimulus was given to different regions of the thalamic central lateral nucleus (CL). Conditioning electrical stimulation in medial (ML 2.8-3.6 mm) parts of CL induced a depression of the TP evoked response in 10 cells. Stimulation sites in lateral CL (ML 3.6-4.2 mm) induced facilitation in eight cells and decreased activity in seven cells. Tooth pulp evoked field potentials in thalamus were facilitated by a preceding stimulation in lateral CL. Cells in the lateral parts of CL are suggested to induce an increased activity in cells in the VB complex which mediate nociceptive information. This effect is suggested to be mediated via a CL induced disinhibition at a reticular thalamic (RE) or at a VB complex level. The medial parts of CL seem to give a traditional feedback inhibition on VB cells. Such an effect is also suggested to be mediated via the RE complex. The importance of these findings are discussed with relation to changes in the thalamus that may occur following long lasting nociceptive stimulation.

Thalamic nociceptive mechanisms in cats, influenced by central conditioning stimuli.

Cortical surface potentials evoked from thalamic intralaminar nuclei have been studied in rats anaesthetized with chloralose. Stimulation with low current intensity in central lateral nucleus (CL), evoked potentials in large areas of the rat isocortex. In the posterior parietal cortex responses with a short latency negativity were evoked which followed high frequency repetitive stimulation. Its latency and ability to follow high frequency stimulation indicated a monosynaptic connection from CL to this part of the cortex. The short latency potential was followed by a second negativity with longer latency and varying amplitude. This second negativity did not follow repetitive stimulation exceeding 10 Hz, and was also reduced by supplementary doses of anaesthetics, indicating a polysynaptic origin. Stimulation at different CL sites elicited cortical potentials with short latency in a topographical pattern. Laminar analysis in the parietal and motor cortex suggested both a superficial and a deep layer termination of afferents from CL. Similar topografical relations and afferent layer distributions have previously been found in cats. The role of the thalamocortical projection from CL to parietal cortex in arousal, attention and pain mechanisms is discussed.

Projection from the thalamic intralaminar nuclei on the isocortex of the rat: a surface potential study.

Evoked responses were mapped in the cerebral cortex following low intensity electrical stimulation in serial penetrations of the medial and intralaminar nuclei of the thalamus of the cat. A projection was found from one of the intralaminar nuclei, the central lateral nucleus (CL) to the midsuprasylvian gyrus, mainly areas 5 and 7. The projection is suggested to be direct, since the evoked responses had a short latency initial positivity. The most characteristic type of response consisted of this early positivity followed by two successive negativities. The earlier, so called first negativity followed high frequency stimulation and was recorded in a smaller area of the cortex than the later, so called second negativity. The first negativity is suggested to depend on monosynaptic depolarization and activation of cortical cells. The second negativity failed at frequencies higher than 10 Hz and was strongly depressed by the administration of barbiturates; it is suggested to depend on polysynaptic depolarization and cellular activity. In electrode penetrations of the cortex both negativities reversed at the border between cortical layers II and III, indicating a superficial termination of thalamic afferents in the cortex. The cortical evoked response to CL stimulation was facilitated by light mechanical and low intensity electrical stimulation of the periphery, as well as by electrical stimulation of the tooth pulp. The possible significance and function of this projection is discussed in relation to arousal, attention and pain.

Localized responses in the midsuprasylvian gyrus of the cat following stimulation of the central lateral nucleus in thalamus.

A previous field potential study has indicated a monosynaptic projection of fibres from the central lateral nucleus (CL) to the mid-suprasylvian gyrus (MSSG). The present study, which is based on an analysis of current source density (CSD), aims to investigate further the sites of major localized synaptic activities in different layers of the MSSG after electrical stimulation in the CL. An initial positive surface potential was evoked in the MSSG with a latency of 3-5 ms and followed by a large negative potential with a peak latency of 8-15 ms. The initial positivity was only found in the rostral part of the MSSG, which corresponds to area 5. The positivity reversed in deeper layers. The CSD analysis showed a sink at a depth from 650 to 1050 microns. A corresponding source was found more superficially at 400-600 microns. This indicates that CL fibres have an excitatory synaptic termination on the soma or proximal dendrites of neurons in layers III and IV. The surface negative potential reversed at the border between layers II and III, suggesting a superficial CL projection. The CSD analysis of potentials in superficial layers showed a sink appearing between the pial surface and a depth of 350 microns, and a source lying in layers below. This indicates a depolarization of apical dendrites of cells in layers II and III. The superficial sink appeared in a large part of the MSSG. Application of a solution of 0.5% gamma-aminobutyric acid (GABA) on the surface of the cortex blocked the superficial sink and source and revealed a prominent sink current in layers III and IV in agreement with a deep termination of CL fibres. Application of a solution of 25 mM DL-2-amino-5-phosphono-valeric acid (APV) abolished CL-evoked cortical responses indicating that N-methyl-D-aspartate (NMDA) receptors are involved in the cortical activation. The CSD analysis confirms that CL has a wide superficial projection to the MSSG. It also confirms a deeper monosynaptic projection from CL to area 5.

B. Rydenhag

Papers

Effects of naloxone on dental pain threshold following muscle exercise and low frequency transcutaneous nerve stimulation: a comparative study in man.

Thalamic nociceptive mechanisms in cats, influenced by central conditioning stimuli.

Projection from the thalamic intralaminar nuclei on the isocortex of the rat: a surface potential study.

Localized responses in the midsuprasylvian gyrus of the cat following stimulation of the central lateral nucleus in thalamus.

Field potential analysis of the cortical projection of the central lateral nucleus in the cat.