A repeating fast radio burst source in a globular cluster.

Fast radio bursts (FRBs) are flashes of unknown physical origin1. The majority of FRBs have been seen only once, although some are known to generate multiple flashes2,3. Many models invoke magnetically powered neutron stars (magnetars) as the source of the emission4,5. Recently, the discovery6 of another repeater (FRB 20200120E) was announced, in the direction of the nearby galaxy M81, with four potential counterparts at other wavelengths6. Here we report observations that localized the FRB to a globular cluster associated with M81, where it is 2 parsecs away from the optical centre of the cluster. Globular clusters host old stellar populations, challenging FRB models that invoke young magnetars formed in a core-collapse supernova. We propose instead that FRB 20200120E originates from a highly magnetized neutron star formed either through the accretion-induced collapse of a white dwarf, or the merger of compact stars in a binary system7. Compact binaries are efficiently formed inside globular clusters, so a model invoking them could also be responsible for the observed bursts.

Anti-N-Methyl-D-Aspartate Receptor Encephalitis: A New Challenging Entity for Consultation-Liaison Psychiatrist.

BACKGROUND: Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is a relatively newly identified autoimmune neuropsychiatric disorder that predominantly affects children and young adults. Although psychiatric symptoms are highly prevalent and frequently severe, it has mainly been reported in neurological, but not psychiatric, literature. Understanding this form of encephalitis, its quick diagnosis and which treatment to provide are of utmost importance for consultation-liaison (C-L) psychiatrists. The aim of this paper was to describe a case of anti-NMDAR encephalitis with severe psychiatric manifestations, who showed impressive recovery but required intensive involvement of the C-L psychiatry team. We emphasise the behavioural aspects, psychiatric symptoms and challenges faced by the CL consultant across the different phases of the treatment. METHODS: We report the different treatment phases for a young woman with anti-NMDAR encephalitis who developed severe neuropsychiatric symptoms, with a focus on the role and challenges faced by the C-L psychiatrist. The literature is reviewed for each of these challenges. RESULTS: This case illustrated that even extremely severely affected patients may show impressive recovery, but require long lasting psychiatric care. C-L psychiatrists are faced with numerous challenges where only little literature is available. CONCLUSION: C-L psychiatrists play a pivotal role throughout the multidisciplinary care of patients with anti-NMDAR encephalitis and should be informed about this entity.

Efficacy of brief interdisciplinary psychotherapeutic intervention for motor conversion disorder and nonepileptic attacks.

OBJECTIVE: The objective was to compare a brief interdisciplinary psychotherapeutic intervention to standard care as treatments for patients recently diagnosed with severe motor conversion disorder or nonepileptic attacks. METHODS: This randomized controlled trial of 23 consecutive patients compared (a) an interdisciplinary psychotherapeutic intervention group receiving four to six sessions by a consultation liaison psychiatrist, the first and last sessions adding a neurological consultation and a joint psychiatric and neurological consultation, and (b) a standard care group. After intervention, patients were assessed at 2, 6 and 12 months with the Somatoform Dissociation Questionnaire (SDQ-20), Clinical Global Impression scale, Rankin scale, use of medical care, global mental health [Montgomery and Asberg Depression Rating Scale, Beck Depression Inventory, mental health component of Short Form (SF)-36] and quality of life (SF-36). We calculated linear mixed models. RESULTS: Our intervention brought a statistically significant improvement of physical symptoms [as measured by the SDQ-20 (P<.02) and the Clinical Global Impression scale (P=.02)] and psychological symptoms [better scores on the mental health component of the SF-36 (P<.05) and on the Beck Depression Inventory (P<.05)] and a reduction in new hospital stays after intervention (P<.05). CONCLUSION: A brief psychotherapeutic intervention taking advantage of a close collaboration with neurology consultants in the setting of consultation liaison psychiatry appears effective.

[Mood disorders in HIV patients: a challenge for liaison psychiatry consultation]. / Troubles de l'humeur et VIH: épidémiologie, clinique et prise en charge thérapeutique.

Mood disorders represent the most prevalent psychiatric condition in patients infected by HIV virus. Screening and treatment of depression as well as the evaluation of the risk suicide is of the utmost importance. When psychopharmacological treatment is required, interaction with antiretroviral treatment must be carefully considered. More generally a close collaboration between the physician and the psychiatrist is recommended.

Complex effects of CNQX on CA1 interneurons of the developing rat hippocampus.

We have investigated the effect of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist, 6-cyano-7-nitro-quinoxaline-2,3-dione (CNQX), on spontaneous GABA(A) receptor-mediated transmission in the hippocampal CA1 subfield. On average, simultaneous recordings from CA1 str. radiatum interneurons and pyramidal cells showed that CNQX application doubled the frequency of bicuculline sensitive spontaneous inhibitory postsynaptic currents (sIPSCs) without apparently changing their amplitude. However, despite the increase in sIPSC frequency, current-clamp recording showed that CNQX application was sufficient in most cases to depolarize interneurons to firing threshold. In contrast, CNQX application could not induce firing in pyramidal cells. In the presence of tetrado-toxin (TTX), CNQX increased interneuron membrane conductance, and depolarized interneurons from resting potentials. The axons of the studied interneurons ramify widely in the CA1 region and suggest that the cells of our sample are mostly involved with control of dendritic excitability. Our results indicate that CNQX-induced increase of sIPSC frequency is not limited to excitatory cells, but also impacts GABAergic interneurons. However, despite the increase of sIPSC frequency, CNQX-induced depolarization is sufficient to selectively generate firing in interneurons and thus modify the network properties mediated by GABA(A) receptors in the hippocampus.

Cholecystokinin-immunopositive basket and Schaffer collateral-associated interneurones target different domains of pyramidal cells in the CA1 area of the rat hippocampus.

Two types of GABAergic interneurone are known to express cholecystokinin-related peptides in the isocortex: basket cells, which preferentially innervate the somata and proximal dendrites of pyramidal cells; and double bouquet cells, which innervate distal dendrites and dendritic spines. In the hippocampus, cholecystokinin immunoreactivity has only been reported in basket cells. However, at least eight distinct GABAergic interneurone types terminate in the dendritic domain of CA1 pyramidal cells, some of them with as yet undetermined neurochemical characteristics. In order to establish whether more than one population of cholecystokinin-expressing interneurone exist in the hippocampus, we have performed whole-cell current clamp recordings from interneurones located in the stratum radiatum of the hippocampal CA1 region of developing rats. Recorded neurones were filled with biocytin to reveal their axonal targets, and were tested for the presence of pro-cholecystokinin immunoreactivity. The results show that two populations of cholecystokinin-immunoreactive interneurones exist in the CA1 area (n=15 positive cells). Cholecystokinin-positive basket cells (53%) preferentially innervate stratum pyramidale and adjacent strata oriens and radiatum. A second population of cholecystokinin-positive cells, previously described as Schaffer collateral-associated interneurones [Vida et al. (1998) J. Physiol. 506, 755-773], have axons that ramify almost exclusively in strata radiatum and oriens, overlapping with the Schaffer collateral/commissural pathway originating from CA3 pyramidal cells. Two of seven of the Schaffer collateral-associated cells were also immunopositive for calbindin. Soma position and orientation in stratum radiatum, the number and orientation of dendrites, and the passive and active membrane properties of the two cell populations are only slightly different. In addition, in stratum radiatum and its border with lacunosum of perfusion-fixed hippocampi, 31.6+/-3.8% (adult) or 26.8+/-2.9% (postnatal day 17-20) of cholecystokinin-positive cells were also immunoreactive for calbindin. Therefore, at least two populations of pro-cholecystokinin-immunopositive interneurones, basket and Schaffer collateral-associated cells, exist in the CA1 area of the hippocampus, and are probably homologous to cholecystokinin-immunopositive basket and double bouquet cells in the isocortex. It is not known if the GABAergic terminals of double bouquet cells are co-aligned with specific glutamatergic inputs. However, in the hippocampal CA1 area, it is clear that the terminals of Schaffer collateral-associated cells are co-stratified with the glutamatergic input from the CA3 area, with as yet unknown functional consequences. The division of the postsynaptic neuronal surface by two classes of GABAergic cell expressing cholecystokinin in both the hippocampus and isocortex provides further evidence for the uniform synaptic organisation of the cerebral cortex.

Cell surface domain specific postsynaptic currents evoked by identified GABAergic neurones in rat hippocampus in vitro.

1. Inhibitory postsynaptic currents (IPSCs) evoked in CA1 pyramidal cells (n = 46) by identified interneurones (n = 43) located in str. oriens were recorded in order to compare their functional properties and to determine the effect of synapse location on the apparent IPSC kinetics as recorded using somatic voltage clamp at -70 mV and nearly symmetrical [Cl-]. 2. Five types of visualised presynaptic interneurone, oriens-lacunosum moleculare (O-LMC), basket (BC), axo-axonic (AAC), bistratified (BiC) and oriens-bistratified (O-BiC) cells, were distinguished by immunocytochemistry and/or synapse location using light and electron microscopy. 3. Somatostatin immunoreactive O-LMCs, innervating the most distal dendritic shafts and spines, evoked the smallest amplitude (26 +/- 10 pA, s.e.m., n = 8) and slowest IPSCs (10-90 % rise time, 6.2 +/- 0.6 ms; decay, 20.8 +/- 1.7 ms, n = 8), with no paired-pulse modulation of the second IPSC (93 +/- 4 %) at 100 ms interspike interval. In contrast, parvalbumin-positive AACs evoked larger amplitude (308 +/- 103 pA, n = 7) and kinetically faster (rise time, 0.8 +/- 0.1 ms; decay 11.2 +/- 0.9 ms, n = 7) IPSCs showing paired-pulse depression (to 68 +/- 5 %, n = 6). Parvalbumin- or CCK-positive BCs (n = 9) terminating on soma/dendrites, BiCs (n = 4) and O-BiCs (n = 7) innervating dendrites evoked IPSCs with intermediate kinetic parameters. The properties of IPSCs and sensitivity to bicuculline indicated that they were mediated by GABAA receptors. 4. In three cases, kinetically complex, multiphasic IPSCs, evoked by an action potential in the recorded basket cells, suggested that coupled interneurones, possibly through electrotonic junctions, converged on the same postsynaptic neurone. 5. The population of O-BiCs (4 of 4 somatostatin positive) characterised in this study had horizontal dendrites restricted to str. oriens/alveus and innervated stratum radiatum and oriens. Other BiCs had radial dendrites as described earlier. The parameters of IPSCs evoked by BiCs and O-BiCs showed the largest cell to cell variation, and a single interneurone could evoke both small and slow as well as large and relatively fast IPSCs. 6. The kinetic properties of the somatically recorded postsynaptic current are correlated with the innervated cell surface domain. A significant correlation of rise and decay times for the overall population of unitary IPSCs suggests that electrotonic filtering of distal responses is a major factor for the location and cell type specific differences of unitary IPSCs, but molecular heterogeneity of postsynaptic GABAA receptors may also contribute to the observed kinetic differences. Furthermore, domain specific differences in the short-term plasticity of the postsynaptic response indicate a differentiation of interneurones in activity-dependent responses.

Free Jet Absorption Millimeter Wave Spectrum of Pyrrolidine: Assignment of a Second, Equatorial, the Most Stable Conformer.

The equatorial conformer of pyrrolidine has been discovered while investigating the rotational free jet spectrum of the pyrrolidine-water adduct. It is more stable than the axial species, previously assigned with conventional microwave spectroscopy (W. Caminati, H. Oberhammer, G. Pfafferott, R. R. Filgueira, and C. H. Gomez, 1984. J. Mol. Spectrosc., 106, 217-266). The assignment of the equatorial conformer was missed in that microwave investigation because of the accidentally zero or almost zero value of its µa dipole moment component; its low J µc-type transitions, very weak in the room temperature spectrum, are the strongest lines in the jet. Copyright 1998 Academic Press.

Target-specific expression of presynaptic mossy fiber plasticity.

Mossy fiber synaptic transmission at hippocampal CA3 pyramidal cells and interneurons was compared in rat brain slices to determine whether mossy terminals are functionally equivalent. Tetanic stimulation of mossy fibers induced long-term potentiation in pyramidal neurons but was either without effect or it induced depression at synapses onto interneurons. Unlike transmission onto pyramidal neurons, transmission onto interneurons was not potentiated after adenosine 3',5'-monophosphate (cAMP) activation. Furthermore, metabotropic glutamate receptor depression of transmission onto interneurons did not involve cAMP-dependent pathways. Thus, synaptic terminals arising from a common afferent pathway do not function as a single compartment but are specialized, depending on their postsynaptic target.

Social interaction and sensorimotor gating abnormalities in mice lacking Dvl1.

Mice completely deficient for Dvl1, one of three mouse homologs of the Drosophila segment polarity gene Dishevelled, were created by gene targeting. Dvl1-deficient mice are viable, fertile, and structurally normal. Surprisingly, these mice exhibited reduced social interaction, including differences in whisker trimming, deficits in nest-building, less huddling contact during home cage sleeping, and subordinate responses in a social dominance test. Sensorimotor gating was abnormal, as measured by deficits in prepulse inhibition of acoustic and tactile startle. Thus, Dvl1 mutants may provide a model for aspects of several human psychiatric disorders. These results are consistent with an interpretation that common genetic mechanisms underlie abnormal social behavior and sensorimotor gating deficits and implicate Dvl1 in processes underlying complex behaviors.

Synaptic plasticity in hippocampal interneurons? A commentary.

The hypothesis that excitatory synapses onto hippocampal inhibitory interneurons undergo forms of synaptic plasticity similar to that observed in principal pyramidal neurons has received much attention in the last few years. No general consensus exists, however, concerning the presence (or absence) of long-term potentiation and depression in nonpyramidal neurons. A large source of this disagreement stems from the experimental paridigms chosen to elicit synaptic plasticity in the various studies, since most of the induction protocols used did not permit the separation of plasticity occurring on principal cells from possible direct plasticity on the interneurons themselves. In this commentary we discuss some of the issues surrounding these data and also address some of the technical considerations one must address before the presence or absence of long-term potentiation in interneurons can be answered unequivocally.

Millimeter-Wave Free Jet Absorption Spectrum of SD Methylthioglycolate: Description of the SH Torsion Double Minimum Potential

The free jet absorption millimeter-wave spectrum of methylthioglycolate-SD has been investigated in the 60-78 GHz frequency range. The double-minimum potential associated with the SD group torsion generates a vibrational spacing Delta01 = 8285(5) MHz between the O+ and O- states of the A sublevel. This splitting, compared to the corresponding value of 18 953 MHz for the normal species, suggests a large involvement of the sulfur atom in the motion. A model is given to describe this motion. Copyright 1997 Academic Press. Copyright 1997Academic Press

The hyperpolarization-activated current (Ih) and its contribution to pacemaker activity in rat CA1 hippocampal stratum oriens-alveus interneurones.

1. The hyperpolarization-activated current (Ih) and its role in pacemaking activity in rat hippocampal stratum oriens-alveus interneurones was studied using whole-cell and perforated patch-clamp configurations. 2. Voltage-clamp recordings revealed Ih as a slowly activating, inward current, activated by hyperpolarizing steps (holding potential, Vh = -40 mV), with a reversal potential close to -30 mV. Its activation curve ranged from approximately -50 to -120 mV with a mid-activation point of -84.1 mV. 3. Ih was blocked by external application of Cs+ (2-5 mM) and ZD7288 (100 microM), but not by Ba2+ (1 mM). 4. Ih was potentiated by both noradrenaline and isoprenaline by a mechanism consistent with a shift in the Ih activation curve. 5. Under current-clamp conditions (Vh = -60 mV), ZD7288 induced a membrane hyperpolarization concomitant with an increase in the membrane input resistance and abolished the voltage sag generated by hyperpolarizing current injection. 6. Analysis of the current-discharge relationship revealed that block of Ih differentially increased the firing frequency of spikes occurring early in the train compared with those occurring late in the discharge. 7. When applied to spontaneously firing cells, ZD7288 reduced the firing frequency by selectively altering the time course of the interspike interval, while minimally affecting other action potential characteristics. Similarly, isoprenaline increased the spontaneous firing frequency by an effect exclusively on the after-hyperpolarization and interspike interval. 8. These results provide evidence for the involvement of Ih in the excitability and generation of spontaneous firing in hippocampal stratum oriens-alveus interneurones.

Long-term potentiation in distinct subtypes of hippocampal nonpyramidal neurons.

We have investigated NMDA receptor-dependent long-term potentiation (LTP) in distinct subtypes of nonpyramidal neurons of the CA1 hippocampus using induction protocols that permitted the differentiation between a direct form of LTP and plasticity resulting simply from the "passive propagation" of LTP occurring on CA1 pyramidal neurons. Two types of stratum (st.) oriens/ alveus interneurons received passive propagation of synaptic potentiation via the recurrent collaterals of CA1 pyramidal cells, but neither subtype possessed direct plasticity. In st. radiatum, two distinct classes of cells were observed: st. radiatum interneurons that showed neither direct nor propagated forms of synaptic plasticity, and "giant cells" for which EPSPs were robustly potentiated after a pairing protocol. This potentiation is similar to the LTP described in pyramidal cells, and its induction requires NMDA receptor activation. Thus, a large heterogeneity of synaptic plasticity exists in morphologically distinct neurons and suggests that complex changes in the CA1 network properties will occur after the induction of LTP.

Passive propagation of LTD to stratum oriens-alveus inhibitory neurons modulates the temporoammonic input to the hippocampal CA1 region.

Excitatory synaptic activity in horizontal stratum oriens-alveus interneurons (OAIs) is driven by the recurrent collaterals of CA1 pyramidal cells and is strongly influenced by protocols that elicit synaptic plasticity in these principal neurons. Induction of LTD in the Schaffer collateral-CA1 pyramidal neuron synapse causes a passive down-regulation of stratum radiatum-evoked excitatory synaptic responses onto OAIs. In addition, we show that the strength of the temporoammonic input to the CA1 pyramidal neuron distal dendrites is regulated by OAI activity. The passive propagation of LTD to OAIs consequently disinhibits the direct entorhinal cortex-CA1 input, resulting in an enhanced excitation of CA1 pyramidal neurons by a mechanism not requiring activation of the trisynaptic pathway.

Cesium prevents maintenance of long-term depression in rat hippocampal CA1 neurons.

Long-term depression of field excitatory postsynaptic potentials (EPSP) in the CA1 region of hippocampal slices was evoked by delivering a 15 min train of pulses at 1 Hz to the Schaffer-commissural-CA1 pathway, and prevented by adding an N-methyl-D-aspartate (NMDA) receptor antagonist (AP-5, 50 microM) to the perfusing medium. Superfusion of the slices with Cs (2 mM) during the 1 Hz stimulation period could both inhibit the maintenance phase of the depression itself and elicit spontaneous rhythmic activity. Cs had no effect on the postsynaptic response to the GABA-B agonist, baclofen. As a major effect of Cs is a block of the hyperpolarization-activated current (Ih), these results suggest the possible involvement of Ih in the maintenance of long-term depression.

Properties of the hyperpolarization-activated current in rat hippocampal CA1 pyramidal cells.

1. Voltage and current clamp recordings were performed on CA1 rat hippocampal pyramidal cells using the patch clamp technique on "in vitro" slice preparations. 2. Hyperpolarizations from a holding potential of -35 mV elicited activation of the hyperpolarization-activated current (Ih) starting at voltages near -50 mV. 3. Ih recorded in voltage clamp conditions was blocked by external caesium (5 mM). 4. Raising the external K concentration from 4.35 to 24.35 mM sensibly increased the slope of the current-voltage (I/V) curve. Decreasing the external Na concentration from 133.5 to 33.5 mM depressed Ih without grossly altering the I/V slope. 5. The Ih fully activated I/V relation measured in the range -140 to -45 mV was linear with an extrapolated reversal at -17.0 +/- -1.6 (SE) mV. The current activation curve comprised the range between about -50 and -140 mV with a half-maximal activation at about -98 mV. 6. Perfusion of unclamped neurons with Cs (2 mM) hyperpolarized their resting potential by 3.8 +/- 0.2 mV and decreased the membrane conductance, as expected if Ih were activated at rest. Firing caused by depolarizing current steps was prevented by Cs-induced hyperpolarization, and could be restored by returning the membrane voltage to resting level by constant current injection. 7. The Cd-insensitive (medium-duration) afterhyperpolarization (AHP) elicited by a train of action potentials at -60 mV had an amplitude of 3.9 +/- 0.3 mV and was nearly fully abolished by 2 mM Cs (82.7 +/- 7.4%). Cs removed the depolarizing part of the afterhyperpolarization as expected if Ih activation was responsible for this phase.(ABSTRACT TRUNCATED AT 250 WORDS)

Intracellular calcium does not directly modulate cardiac pacemaker (if) channels.

A study on the cardiac pacemaker current if in inside-out macro-patches of sino-atrial (SA) node cells has recently demonstrated that if channels are directly activated by intracellular cAMP. Using the same preparation, here we investigate the possibility that internal Ca2+ ions play a role in the modulation of if channels. Our results indicate that Ca2+ ions do not have a direct activating effect on if.

Block of the cardiac pacemaker current (If) in the rabbit sino-atrial node and in canine Purkinje fibres by 9-amino-1,2,3,4-tetrahydroacridine.

We have investigated the action of 9-amino-1, 2, 3, 4-tetrahydroacridine (THA) on the pacemaker current If in rabbit sino-atrial node myocytes and in canine Purkinje fibers. THA at concentrations in the range 3-300 microM blocked If in a voltage-independent manner, as revealed by measurements on the fully activated I/V relation for If. The dose/response relationship of the If maximal slope conductance (Gf) can be fitted by assuming a cooperative binding reaction where two THA molecules are required to block one If channel. Half-maximal block occurred at 18.2 microM in the sino-atrial node and 36.6 microM in Purkinje fibers. THA also affected the If kinetic properties. This was examined in the sino-atrial node where the current activation curve was shifted in the negative direction on the voltage axis (- 21 mV at 30 microM THA). The delayed rectifier current, IK, was also reduced by THA in sino-atrial node myocytes: at - 40 mV the IK fully activated value was decreased to 37% of its control value by 30 microM THA, with only a minor modification of the position of the activation curve at the same potential. Thus, although THA blocks If at a lower concentration than other known If-channel blockers [DiFrancesco (1982) J Physiol (Lond) 329:485-507], its action on the pacemaker current is not specific.