Vasopressin modulates social recognition-related activity in the left temporoparietal junction in humans

The neuropeptide vasopressin is a key molecular mediator of social behavior in animals and humans, implicated in anxiety and autism. Social recognition, the ability to assess the familiarity of others, is essential for appropriate social interactions and enhanced by vasopressin; however, the neural mechanisms mediating this effect in humans are unknown. Using functional magnetic resonance imaging (fMRI) and an implicit social recognition matching task, we employed a double-blinded procedure in which 20 healthy male volunteers self-administered 40 UI of vasopressin or placebo intranasally, 45 min before performing the matching task in the scanner. In a random-effects fMRI analysis, we show that vasopressin induces a regionally specific alteration in a key node of the theory of mind network, the left temporoparietal junction, identifying a neurobiological mechanism for prosocial neuropeptide effects in humans that suggests novel treatment strategies

Effects of extracellular calcium and of light adaptation on the response to dim light in honey bee drone photoreceptors.

Light responses in honey bee drone photoreceptors were recorded with intracellular micro-electrodes in superfused slices of retina. The effects of changes in extracellular calcium on the size and the shape of the response to dim light were studied and compared with the effects of light adaptation. Dim light stimuli were used so that the amplitude of the response was linearly related to the number of the photons absorbed, the effects of voltage-dependent mechanisms were negligible and no detectable light adaptation was produced by the stimulus. Lowering the extracellular calcium concentration increased the amplitude and the duration of the response. Raising the extracellular calcium concentration produced the opposite effects. Changing the extracellular calcium concentration modified the response without altering either the linearity of the intensity--response relation or the resting membrane potential in the dark. Light adaptation decreased the amplitude and the duration of the response in a manner that could be quantitatively simulated, in the same photoreceptors, by an increase in the extracellular calcium concentration. Changing the extracellular calcium concentration, or light-adapting the preparation, modified the response without altering its early depolarizing phase. Lowering external calcium either did not affect, or slightly increased, the maximum rate of the light-induced depolarization; raising external calcium, or light-adapting the preparation, either did not affect, or slightly decreased, the maximum rate of the light-induced depolarization. The experimental data can be quantitatively described by a mathematical model with the basic assumption that calcium acts in the process of light adaptation by decreasing the mean open time of the light-activated channels

Oxytocin receptor agonists enhance inhibitory synaptic transmission in the rat hippocampus by activating interneurons in stratum pyramidale

Oxytocin probably plays a role as a neurotransmitter/neuromodulator in the hippocampus of the rat. Oxytocin binding sites are present in the subiculum and CA1 region and oxytocin can excite a class of CA1 nonpyramidal neurons. In the present work we characterized the effect of oxytocin on hippocampal synaptic transmission. Whole-cell recordings were obtained from pyramidal neurons, in conditions of nearly symmetrical chloride concentrations. The selective oxytocin receptor agonist, [Thr4,Gly7]-oxytocin (TGOT), caused an increase in the frequency and amplitude of spontaneous inhibitory postsynaptic currents (IPSCs) in virtually all neurons. These peptide-enhanced IPSCs were blocked by bicuculline, but not by strychnine, and reversed near 0 mV, indicating that they were mediated by gamma-aminobutyric acid (GABA)A receptors. On average, TGOT caused a nearly threefold increase in the frequency and almost a doubling in the amplitude of spontaneous IPSCs. TGOT did not influence the frequency and the amplitude of miniature IPSCs or spontaneous excitatory postsynaptic currents (EPSCs), and had no effect on evoked IPSCs. The peptide did not affect the basic membrane properties of pyramidal neurons or their GABA sensitivity. Thus, TGOT facilitated inhibitory transmission by exerting an excitatory action on the soma and/or dendrites of GABAergic interneurons. Extracellular recordings were performed in interneurons located in various hippocampal strata. Their sensitivity to TGOT was compared to that of substance P (SP). Interneurons in stratum pyramidale were excited both by TGOT and by SP. By contrast, stratum radiatum interneurons responded to SP but not to TGOT. In stratum oriens, half of the interneurons responded to SP, but only a minority to TGOT. Thus, oxytocin-responsive interneurons appear to be preferentially located in close vicinity of pyramidal neurons

Mechanism of action of oxytocin in rat vagal neurones: induction of a sustained sodium-dependent current.

1. The mechanism of action of oxytocin on vagal neurones of the rat was studied using single-electrode voltage-clamp recordings from brainstem slices. The ionic basis of the oxytocin-induced current was examined by changing the composition of the perfusion solution and by making use of channel blockers. 2. In neurones clamped at or near their resting potential, oxytocin generated a sustained, TTX-insensitive inward current whose peak amplitude was concentration related. This current was detectable at 10 nM, was half-maximal at about 100 nM and was maximal at micromolar concentrations of peptide. 3. The oxytocin current was inward over membrane potentials ranging from -110 to -20 mV and was voltage dependent, since it increased in magnitude as the membrane was depolarized from the resting potential toward less negative potentials. 4. Partial replacement of extracellular sodium by equimolar N-methyl-D-glucamine reversibly attenuated or suppressed the oxytocin current. By contrast, substituting part of extracellular chloride or blocking calcium currents did not modify it. Increasing the transmembrane potassium gradient was also without effect and none of the potassium channel blockers TEA, 4-amino pyridine (4-AP), apamin, caesium or barium affected the oxytocin current. This current is thus at least in part carried by sodium. 5. The activation of the oxytocin current as a function of the membrane potential could be quantitatively simulated using a Boltzmann equation, suggesting that oxytocin acts by inducing the opening of a voltage-dependent channel which can exist in either of two states, open or closed. 6. Lowering the extracellular calcium concentration from 2 to 0.1 mM, while keeping the magnesium concentration constant at 1 mM, enhanced the response to oxytocin. This low calcium-induced potentiation of the oxytocin current was 1.4-3-fold and was reversible. 7. We conclude that oxytocin increases the excitability of vagal neurones by generating a persistent, voltage-gated current which is sodium dependent, is insensitive to TTX and is modulated by divalent cations

Tachykinins and bombesin excite non-pyramidal neurones in rat hippocampus.

The effects of substance P, eledoisin and physalaemin--which are structurally similar and all belong to the tachykinin family--and of bombesin, a gastrin-releasing peptide, on non-pyramidal neurones were studied using unitary extracellular recordings from rat hippocampal slices. The peptides were added to the perifusion solution, or locally applied by pressure ejection from a micropipette, at concentrations ranging from 10(-8) to 10(-6) M. 104 out of 115 non-pyramidal neurones responded to tachykinins, and 26 out of 27 responded to bombesin, by a reversible, concentration-dependent increase in firing. The responsive neurones retained their sensitivity to the tachykinins and to bombesin under the condition of synaptic blockade. A synthetic peptide known to antagonize the effects of oxytocin on hippocampal non-pyramidal neurones did not affect the excitations induced by the tachykinins or bombesin. The action of the tachykinins was not blocked by the muscarinic antagonist, atropine. These results indicate that hippocampal non-pyramidal neurones--which were previously shown to possess oxytocin receptors and mu-type opiate receptors--bear receptors for peptides of the tachykinin and of the gastrin-releasing families. The hippocampal effects of tachykinins and of bombesin, however, were not blocked by synthetic structural analogues of substance P, known to antagonize the action of these peptides on some non-nervous tissues. The possibility must be considered that brain receptors for tachykinins and for gastrin-releasing peptides may be distinct from the peripheral receptors for these peptides

Low-threshold Na+ currents: a new family of receptor-operated inward currents in mammalian nerve cells

In the mammalian nervous system, various neurotransmitters can modulate cell excitability by inducing slow membrane potential changes. In the last decade, inhibition of potassium currents has been characterized as the primary mechanism by which neurones can undergo sustained depolarization. More recently (1990s), a new class of inward currents, which are voltage-dependent and mainly carried by sodium ions, has been found to be activated by various neurotransmitter receptors in mammalian central and peripheral neurones. Because the channels involved pass depolarizing current, are open at more negative membrane potentials than the resting potential, and are voltage-gated and persistent, these currents are capable of producing regenerative and maintained depolarizations and play an important role in neuronal signalling

Suppression of potassium channels elicits calcium-dependent plateau potentials in suprachiasmatic neurons of the rat

By using whole-cell recordings in acute and organotypic hypothalamic slices, we found that following K+ channel blockade, sustained plateau potentials can be elicited by current injection in suprachiasmatic neurons. In an attempt to determine the ionic basis of these potentials, ion-substitution experiments were carried out. It appeared that to generate plateau potentials, calcium influx was required. Plateau potentials were also present when extracellular calcium was replaced by barium, but were independent upon an increase in the intracellular free calcium concentration. Substitution of extracellular sodium by the impermeant cation N-methyl-D-glucamine indicated that sodium influx could also contribute to plateau potentials. To gain some information on the pharmacological profile of the Ca++ channels responsible for plateau potentials, selective blocker of various types of Ca++ channel were tested. Plateau potentials were unaffected by isradipine, an L-type Ca++ channel blocker. However, they were slightly reduced by omega-conotoxin GVIA and omega-agatoxin TK, blockers of N-type and P/Q-type Ca++ channels, respectively. These data suggest that R-type Ca++ channels probably play a major role in the genesis of plateau potentials. We speculate that neurotransmitters/neuromodulators capable of reducing or suppressing potassium conductance(s) may elicit a Ca++-dependent plateau potential in suprachiasmatic neurons, thus promoting sustained firing activity and neuropeptide release

Vasopressin facilitates glycinergic and GABAergic synaptic transmission in developing hypoglossal motoneurons

The hypoglossal nucleus of young rats contains vasopressin binding sites and vasopressin can directly excite hypoglossal motoneurons. In addition, indirect evidence suggests that vasopressin can enhance the synaptic input to motoneurons. We have characterized this latter effect by using brainstem slices and whole-cell recordings. We found that, in the presence of blockers of fast glutamatergic transmission, vasopressin strongly facilitated inhibitory synaptic activity. On average, vasopressin caused a six-fold increase in the frequency and a 1.5-fold increase in the amplitude of GABAergic postsynaptic currents. The effect of vasopressin on glycinergic postsynaptic currents was similar in magnitude. Vasopressin did not affect the frequency of GABAergic or glycinergic miniature postsynaptic currents, indicating that the peptide-induced facilitation of inhibitory transmission was mediated by receptors located on the somatodendritic region rather than on axon terminals of presynaptic neurons. The pharmacological profile of these receptors was determined by using d[Cha4]AVP and dVDAVP, selective agonists of V1b and V2 vasopressin receptors, respectively, and Phaa-D-Tyr-(Et)-Phe-Gln-Pro-Arg-Arg-NH2, a selective antagonist of V1a vasopressin receptors. The two agonists had no effect on the frequency of inhibitory postsynaptic currents. By contrast, the antagonist suppressed the vasopressin-induced facilitation of these currents, indicating that the receptors involved were exclusively of the V1a type. Thus, vasopressin exerts a dual action on hypoglossal motoneurons: a direct excitatory action and an indirect action mediated by GABAergic and glycinergic synapses. By virtue of this dual effect, vasopressin could alter the input-output properties of these motoneurons. Alternatively, it could play a role in generating or modulating specific motor patterns