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S Landgren

Publications and source records attributed to S Landgren.

At least 19 recordsLinked to original sources

The inhibitory effects of allopregnanolone and pregnanolone on the population spike, evoked in the rat hippocampal CA1 stratum pyramidale in vitro, can be blocked selectively by epiallopregnanolone.

The progesterone metabolites allopregnanolone (Allo, 3alpha-hydroxy-5alpha-pregnan-20-one) and pregnanolone (Preg, 3alpha-hydroxy-5beta-pregnan-20-one) enhance the gamma-aminobutyric acid (GABA) action through a distinct site on the GABAA-receptor. Their 3beta-isomers epiallopregnanolone (Epiallo, 3beta-hydroxy-5alpha-pregnan-20-one) and epipregnanolone (Epipreg, 3beta-hydroxy-5beta-pregnan-20-one), do not have these effects on GABAA-receptors. We have studied the interaction between Allo/Preg and their 3beta-isomers on action potentials in rat hippocampal slices in vitro. The Schaffer collaterals were stimulated electrically in CA1 striatum radiatum and the population spike (POPSP) was recorded in stratum pyramidale. A 0.5-nL droplet of drug was applied locally onto stratum oriens-pyramidale via a pressure pipett. Muscimol (Mus) (12.5 fmol), Allo and Preg (6.25 fmol) caused a reversible inhibition of POPSP. On the other hand, 6.25 fmol Epiallo had no significant effect on POPSP compared with the vehicle control. Combined Epiallo and Allo application caused a dose-dependent reduction of the Allo inhibition of POPSP. A full blockage was seen at a molar ratio of 1:1. Epiallo also blocked the Preg inhibition of POPSP, when the two drugs were combined in a molar ratio of 1:1. Epiallo did not block the Mus inhibition of POPSP, when the two drugs were combined at a molar ratio of 1:2. Bath perfusion of 12.5 microM Epiallo blocked the inhibition of 6.25 fmol Allo on POPSP, but not the inhibition caused by 12.5 fmol Mus. Epipreg did not block the inhibition of Allo and Preg on POPSP, when it was combined with the two latter drugs at a molar ratio of 1:1. Our data suggest that the steroid modulation of the GABAA transmitted inhibition of the CA1 pyramidal neurones is selectively and dose dependently blocked by Epiallo, the 3beta-hydroxy-isomer of Allo, but not by Epipreg, the 3beta-hydroxy-isomer of Preg.

Action Potentials↗

Interaction between 3 alpha-hydroxy-5 alpha-pregnan-20-one and carbachol in the control of neuronal excitability in hippocampal slices of female rats in defined phases of the oestrus.

The effects of 3 alpha-hydroxy-5 alpha-pregnan-20-one (allopregnanolone) and carbachol on CA1 and dentate gyrus action potentials were studied in hippocampus slices in premature, follicular and luteal phase rats. A 0.5 nL droplet of allopregnanolone (12.5 mumol L-1), carbachol (5 mumol L-1) or a mixed solution of 12.5 mumol L-1 allopregnanolone and 5 mumol L-1 carbachol was applied locally onto the stratum oriens-pyramidale or granular layer. The amplitude of CA1 population spike (POPSP) was reduced by allopregnanolone (-38 +/- 3%) and carbachol (-21 +/- 4%) in the luteal phase slices. The mixture of allopregnanolone and carbachol doubled this inhibition (-77 +/- 6%). The inhibition caused by allopregnanolone and the mixture of allopregnanolone and carbachol in CA1 was significantly larger in the luteal phase than in the follicular phase (P = 0.02 and 0.0002). In the granular layer of the dentate gyrus, these inhibitions showed no significant difference between the phases. Neither in CA1 nor in the dentate gyrus did the carbachol inhibition differ between the phases. Perfusion with 5-10 mumol L-1 carbachol caused an increasing inhibition of the POPSP during the first few minutes. Thereafter the inhibition gradually diminished and was replaced by a facilitation. The local allopregnanolone inhibition was enhanced by simultaneous carbachol perfusion. Picrotoxin (100 mumol L-1) substantially reduced the allopregnanolone but not the carbachol inhibition. Atropine (10 mumol L-1) blocked the carbachol response, but not the allopregnanolone inhibition. Perfusion with a mixed solution of picrotoxin and atropine reduced, but did not block, the inhibition caused by local application of allopregnanolone or by the mixture of allopregnanolone and carbachol. Our data suggest that neuroprogestine modulators of the GABAA-receptor-mediated inhibition may play a significant role in the control of the cholinergic excitation in the hippocampus.

Action Potentials↗

Interaction between 17 beta-oestradiol and 3 alpha-hydroxy-5 alpha-pregnane-20-one in the control of neuronal excitability in slices from the CA1 hippocampus in vitro of guinea-pigs and rats.

The effect of 17 beta-oestradiol and 3 alpha-hydroxy-5 alpha-pregnane-20-one (allopregnanolone) on the action potentials in the Schaffer collateral pathway was investigated in hippocampus CA1. Slices from male and female guinea-pigs and female rats were used. In the rat three groups were studied: (a) untreated prepubertal rats at day 25 after partus; (b) rats injected on day 26 with 10 IU of equine serum gonadotropin studied on day 28, when in the pro-oestrus follicular phase; and (c) on day 32 when in the luteal phase. The allopregnanolone (12.6 microM, 0.5 nL) was applied locally in stratum orienspyramidale. the 17 beta-oestradiol (0.7 nM) was perfused (4 mL min-1) or applied locally. The amplitude of the population spike in stratum pyramidale was increased by oestradiol in guinea-pigs of both sexes and in all the three groups of rats. Allopregnanolone decreased the amplitude of the population spike in the guinea-pigs and in the luteal phase rats. The effect appeared within seconds after the application of the drugs. The allopregnanolone inhibition of the population spike was increased by perfusion with oestradiol in the guinea-pigs and in the luteal phase rats. This effect appeared within 7 min, and improved with increasing length of the perfusion (7-71 min). It remained for 55 min after return to perfusion with artificial cerebrospinal fluid. In prepubertal and follicular phase rats the allopregnanolone inhibition was seen only after perfusion with oestradiol for more than 15 min. The results show that 17 beta-oestradiol increases the allopregnanolone inhibition and that this inhibition is most efficient during the luteal phase of the rat.

Action Potentials↗

The effect of progesterone and its metabolites on the interictal epileptiform discharge in the cat's cerebral cortex.

The antiepileptic effect of progesterone, 5-alpha-pregnane-3,20-dione, 3-alpha-hydroxy-5-alpha-pregnane-20-one, and 3-alpha-hydroxy-5-beta-pregnane-20-one were tested in an experimental animal model, and compared with the effect of clonazepam. The steroids were dissolved in serum from ovariectomized cats. Ovariectomized adult cats were used and spontaneous epileptic discharges were generated by placing small pieces of penicillin-soaked filter papers on the ipsi and contralateral cerebral cortex. The frequency and amplitude of the interictal epileptiform spikes were recorded, and analysed in a computer. The changes in frequency and amplitudes were calculated. The drugs were infused during 20-s periods into one cerebral hemisphere via the ipsilateral lingual artery with speeds of 1.1, 3.4 and 6.3 ml min-1. A penicillin focus on the contralateral hemisphere served as a simultaneous control. Progesterone and clonazepam showed similar inhibitory effects on epileptiform interictal spiking (median reduction of spike frequency 21%, cf. Table I). The 5-alpha-pregnane-3, 20-dione was generally less potent than progesterone (median reduction 9%) and the 5-alpha- and 5-beta-pregnanolones were two to three times more potent than progesterone (54-66% reduction). The latency of the inhibitory effect was 4-10 s measured from the entrance of the infusion into the lingual artery. The depression lasted 10-20 min. It is concluded that the pregnanolones have strong antiepileptic properties. The rapid onset of effect indicates that the steroids may interact with the neuronal function at the membrane or synaptic levels.

5-alpha-Dihydroprogesterone↗

Location of, and peripheral convergence on, the interneuron in the disynaptic path from the coronal gyrus of the cerebral cortex to the trigeminal motoneurons in the cat.

Primary afferent and descending cortico-bulbar convergence on 186 interneurons located in the intertrigeminal area was investigated. The experiments were performed on cats anaesthetized with chloralose. Nerves from the three trigeminal dermatomes were stimulated electrically at intensities below and above twice the threshold level. Nerves from oral, perioral and periorbital structures, and afferents from the masseteric and digastric muscles were included. The surface of the cerebral cortex was stimulated electrically in systematically selected, maximally receptive points within the trigeminal primary projection fields. The intertrigeminal neurons generally responded to stimulation of low-threshold afferents from periodontal, lingual or perioral cutaneous receptors with a polysynaptic latency. Inputs from 3-5 nerves were common but one afferent input was usually most effective. The neurons were generally discharged from two or more cortical points, as a rule those of the oral and perioral projection fields in areas 3a and 3b of the coronal gyrus. The fastest path from the cerebral cortex to the intertrigeminal area was monosynaptic. However, the median latency was 4-5 ms which indicates an oligosynaptic path. The path went through the pyramid at the pontine level. The discharge pattern of the intertrigeminal neurons was 1-4 spikes in 54% of the neurons and a high frequency train of spikes in 46%. Cortical excitation followed by inhibition of the neurons was observed. The neurons were not discharged by electrical stimulation in the defence-attack area of the hypothalamus. Transsynaptic responses evoked from the mesencephalon were seen in 1/3 of the tested neurons.

Action Potentials↗

Bulbar neurones with axonal projections to the trigeminal motor nucleus in the cat.

The location of bulbar neurones with axons projecting to the ipsi- and contralateral trigeminal motor nucleus were investigated in cats anaesthetized with sodium pentobarbital. Wheat germ agglutinin-conjugated horseradish peroxidase (WGA-HRP) was injected in amounts of 5-24 nl. A volume-calibrated microelectrode was used for recording of evoked potentials and pressure injection of WGA-HRP. The injection site was guided by the position where a maximal antidromic response was evoked by electrical stimulation of the masseteric nerve. The survival time was 19-22 h. In preparations with the depot located in the masseteric subnucleus retrogradely stained neurones were found bilaterally in the borderzone of the trigeminal motor nucleus. Dense populations of stained neurones were observed ipsi- and contralaterally in the dorsal division of the main sensory trigeminal nucleus and the subnucleus-gamma of the oral nucleus of the spinal trigeminal tract. Clusters of WGA-HRP-neurones were observed bilaterally in the lateral tegmental field at the level of the subnucleus-beta of the oral nucleus of the spinal trigeminal tract, bilaterally dorsal to the facial nucleus and contralaterally adjacent to the hypoglossal nucleus. No stained neurones were found in the gigantocellular reticular nucleus. A group of stained neurones was located in the marginal nucleus of brachium conjunctivum and some were found in the raphé nuclei near obex. Cell profiles were of two types: medium-sized neurones with a triangular profile and 30-40 micron diameter, and fusiform neurones 10 X 50-70 micron. Convergence of descending cortical and trigeminal afferent inputs on interneurones located in the lateral borderzone of the trigeminal motor nucleus, i.e. the intertrigeminal area, is reported in the preceding paper.

Animals↗

A method for recording effects of anti-epileptic drugs on interictal discharge in the cat's cerebral cortex. Factors determining the distribution of external carotid artery infusions.

The method utilizes infusion via the external carotid (ECA), the internal maxillary arteries and their anastomoses to the cerebral circulation. It takes into account the ipsilateral distribution of the carotid blood supply. A regular interictal epileptiform spiking from foci on both hemispheres was provided by local application to the cortical surface of small pieces of filter paper soaked in sodium benzylpenicillin, 100,000 IE ml-1. The infused drug affects the ipsilateral foci, and the contralateral one functions as a simultaneous untreated control. The stability of the interictal frequency and the effect of non-oxygen carrying solvents are described. The effect of changes in blood pressure, temperature and PCO2 are considered as well as the coupling between activity in ipsi- and contralateral foci. Experiments with infused radioactive microspheres were performed to determine the strictness of the ipsilateral distribution and the conditions under which it was upheld. With mean arterial blood pressures between 70 mm Hg and 170 mm Hg and infusion speeds between 1.0 ml min-1 and 6.3 ml min-1 the distribution to the contralateral cerebral hemisphere was 0.3% (SD 0.2, SEM 0.1). Infusions of [125I]albumin were used to determine the blood flow in ECA. The flow varied between 20 ml min-1 and 68 ml min-1. The higher values were seen when the extracerebral shunting was high. Conditions influencing the dilution of the infusion and its distribution within the brain were investigated. Important factors were carotid and cerebral blood flow, arterial blood pressure, speed and duration of the infusion, recirculation and cerebral temperature. Arterial PCO2, pH and PO2 should be carefully controlled. Computer-supported treatment of interictal spike frequency and amplitude, as well as of circulatory and respiratory parameters, was utilized. The method was tested in experiments with infusions of 5 alpha-pregnanolone. It was shown that infusions, shorter than the estimated circulation time, reduced the interictal spike frequency and amplitude recorded from the ipsilateral foci without effects on the contralateral ones.

Animals↗

Low threshold afferent projections from the oral cavity and the face to the cerebral cortex of the cat.

The projections of low threshold afferents from the oral cavity and the face to the cerebral cortex of cats anaesthetized with chloralose were investigated. The projection fields of the ipsi- and contralateral lingual, inferior alveolar, mental, superior alveolar, infraorbital, (separate branches from whiskers and nose), ophthalmic, great auricular and the contralateral superficial radial nerves were localized. Surface potentials of short latency and maximal amplitude were recorded and their location traced on photographs of the rostral part of the right cerebral hemisphere. Reference points were indicated with india ink punctures. The extent of the cytoarchitectonic areas was determined on histological serial sections and the borders transferred to the photographs of the hemisphere. The features of the projections were related to the cytoarchitecture and to the pattern of the gyri and sulci. It was observed that the low threshold afferents from the oral cavity and the face projected via fast conducting, presumably three synaptic paths, to separate locations in areas 3a, 3b, 5a and 6a beta. The projections to area 3b were somatotopically organized starting with the auricular and the ophthalmic nerve projections lateral to the 3b projection of the forelimb in the posterior sigmoid gyrus and continuing with the maxillary nose, maxillary whiskers, mental nerve, superior alveolar, inferior alveolar and lingual nerve fields along the coronal gyrus towards the presylvian sulcus. The somatotopy was, however, not isomorphic with the body surface but displayed consecutive, overlapping bands across area 3b. The projections to area 3a were similarly organized. The somatotopy was less obvious in area 5a and 6a beta. Convergent projections with responses of slightly longer latency were observed in area 43 (gyrus orbitalis).

Afferent Pathways↗

Facilitation and inhibition of jaw reflexes evoked by electrical stimulation of the cat's cerebral cortex.

The effects of electrical stimulation of the cerebral cortex on the monosynaptic jaw closing and the disynaptic jaw opening reflexes were studied in cats anaesthetized with chloralose. The time course of the reflex effects was recorded. Similar rhythmic sequences of facilitation and inhibition were observed in both reflexes (Fig. 3). The sequence could start with facilitation or inhibition. The latency of the initial effects was short (2.5 ms) indicating a minimum of two synapses in the descending path. The period of the rhythmic sequence was approximately 10 ms. Optimal parameters for the conditioning cortisol stimuli were found to be: trains of 3-5 surface anodal pulses, 0.5 ms, 400 Hz. The threshold of the cortical effects on the reflexes was 0.3 mA. A single pulse evoked effects. The cortical origin of the effects was located and related to the somatosensory projections, and to the cytoarchitecture. The effects of largest amplitude and most complex time course were evoked from the oral and perioral projections to areas 3a and 3b. Effects evoked from areas 4 gamma, 5a, and 6a beta were less complex and of lower amplitude. It is suggested that a trigemino-cortico-trigeminal loop via 3a may function in reflex modulation of the jaw movements. In addition area 3a may contribute to cortico-cortical motor elaborations via U-fiber connections to area 4 gamma.

Animals↗

The effect of electrical stimulation in the hypothalamus on the monosynaptic jaw closing and the disynaptic jaw opening reflexes in the cat.

The effects of electrical stimulation in the hypothalamus on the monosynaptic jaw closing and the disynaptic jaw opening reflexes were investigated in cats anaesthetized with chloralose. The hypothalamic electrodes were located by observation of behavioural attack responses in the unanaesthetized animal and by means of Horsley-Clarke coordinates. The locations were verified in histological serial sections. Hypothalamic conditioning with trains of 3--10 pulses, 0.5 ms duration, 0.5 mA, 500 Hz, evoked a strong facilitation of the jaw closing reflex and a facilitation followed by an inhibition of the jaw opening reflex. These effects differed from those elicited from the cerebral cortex. The hypothalamic effects had a longer latency (11--13 ms) and required a longer train of conditioning stimuli than was the case with those evoked from the cortex. Bilateral ablation of the sensorimotor cerebral cortex or lesion of the pyramids at the lower pontine level diminished but did not abolish the hypothalamic effects. They did, however, disappear after lesions including the ventral midbrain tegmentum. The stimulus positions eliciting the largest hypothalamic effects on the jaw reflexes were located in a region extending medio-laterally from the perifornical area to the entrance of the ansa lenticularis in the lateral hypothalamus. Rostro-caudally the location was found at the level of the ventromedial hypothalamic nucleus and the anterior hypothalamus just rostral to this nucleus. The region corresponds to those parts of the hypothalamus from which agonistic and feeding responses have been evoked. It is suggested that the observed hypothalamotrigeminal mechanism may exercise a tonic influence on the trigeminal motoneurones, thereby controlling the set point of the biting force. The implications of this hypothesis on the etiology of bruxism and the myofascial pain dysfunction are discussed.

Animals↗

The effect of progesterone on the spontaneous interictal spike evoked by the application of penicillin to the cat's cerebral cortex.

The effect of intravenous infusion of progesterone and Mebumal (ACO, Sweden; penotobarbital, INN) on the frequency and amplitude of the spontaneous interictal spikes from a penicillin focus in the cerebral cortex was investigated in ovariectomized cats anaesthetized with chloralose. The plasma concentration of progesterone was determined. It was found that the generation of penicillin spikes was depressed by progesterone in plasma concentrations as low as 40 ng/ml. Equimolar doses of Mebumal were less effective.

Animals↗

Localization of evoked potentials in the digastric, masseteric, supra- and intertrigeminal subnuclei of the cat.

Extracellular focal potentials were evoked and mapped in the trigeminal motor nucleus and its surrounding borderzone in the cat. Graded electrical stimulation was used for orthodromic and antidromic excitation of the masseteric and digastric motoneurones and for orthodromic stimulation of the lingual and inferior alveolar nerves. The method of referring Horsley Clarke coordinates of microelectrode recording positions to their location of the actual histological section was studied and the total error affecting the method was calculated for the H, AP and L axes. The characteristics and the distribution of the evoked focal potentials were described and related to the histological section from the actual experiment. A phase reversal of the negative focal potential evoked by the lingual and inferior alveolar nerves in the main sensory nucleus and in the intertrigeminal nucleus was observed to indicate the dorso-lateral border of the motor nucleus. Other borders were given by the antidromic potentials evoked in the nucleus. Digastric motoneurones were found medially in the caudal third and ventro-medially in the middle third of the motor nucleus. The masseteric motoneurones were located laterally in the middle and rostral thirds of the nucleus. Potentials evoked in the supratrigeminal and intertrigeminal subnuclei, adjacent to the motor nucleus, were considered and discussed in relation to the available evidence of interneurones subserving trigeminal reflex arcs.

Action Potentials↗

Columnar distribution of U-fibres from the postcruciate cerebral projection area of the cat's group I muscle afferents.

Needle stitch lesions were made in the maximal point of the cerebral projection area of the low threshold muscle afferents near the postcruciate dimple of the cat's posterior sigmoid gyrus. The lesions did not exceed 500 mum in diameter and were restricted to the cortical grey matter. Degenerating nerve fibres and terminals were investigated with Fink-Heimer technique in four cats (survival times: 26, 48 and 96 hours). The cytoarchitectonic areas of the sensori-motor cortex were determined in cresyl violet and van Gieson sections. All lesions were made in area 3a. Degenerating U-fibres originating from the lesion travelled in the white matter to the cortex of area 4 gamma, 3b and 2. They reentered the cortex and branched in layer III. Terminal degeneration was found in layer I. The degeneration was distributed to distinct columns with a diameter of about 1mm. Such columns were observed laterally and medially in area 4 gamma, in area 3b near the caudal end of the coronal sulcus, in area 2 near the lateral ansate sulcus and in the forelimb region of SII. The distribution of the cortico-cortical connections from the cerebral projection area of the forelimb group I muscle afferents was discussed in relation to the known cerebral projections of group I muscle afferents, low threshold joint afferents, pacinian afferents and low threshold skin afferents.

Animals↗

Nucleus Z, the medullary relay in the projection path to the cerebral cortex of group I muscle afferents from the cat's hind limb.

1. The medullary relay of hind limb muscle afferents was studied in cats anaesthetized with chloralose. Evoked potentials were recorded from the dorsal surface of the medulla oblongata and from the depth of the medulla with penetrating micro-electrodes. Graded electrical stimulation of the muscle nerves was used. The afferent volley was monitored by recordings from the lumbar dorsal roots or from the peripheral nerves.2. Group I muscle afferents from the ipsilateral quadriceps, posterior biceps-semitendinosus and gastrocnemius-soleus nerves evoked potentials in the nucleus Z of Brodal & Pompeiano (1957a). Focal and unitary potentials were recorded within 2.7-3.8 mm rostral to the obex and 2.8-4.1 mm lateral to the mid line. The recording positions were checked histologically.3. Focal and unitary responses appeared at threshold strengths of the afferent volleys. The latencies of the focal potentials varied between 4.5 and 7.0 msec, those of the unitary ones between 5.1 and 11.0 msec. Group II muscle afferents and low threshold cutaneous afferents also projected to nucleus Z.4. An antidromic discharge was evoked in the relay cells of nucleus Z by electrical stimulation of the contralateral thalamus.5. A lesion of nucleus Z abolished the response evoked in the contralateral post-sigmoid gyrus of the cerebral cortex by the Group I muscle afferents of the hind limb.6. A superficial transection of the ipsilateral dorsolateral fascicle at the 1st cervical segment abolished the potentials evoked in nucleus Z.7. Results of lumbar cord transections showed that most of the primary afferents of the Group I hind limb path supplying nucleus Z enter the dorsolateral fascicle at L3 level.8. The relation of the Group I hind limb path to the dorsal spinocerebellar tract is discussed.

Action Potentials↗