Spatial and Temporal Dynamics in the Ionic Driving Force for GABAA Receptors

It is becoming increasingly apparent that the strength of GABAergic synaptic transmission is dynamic. One parameter that can establish differences in the actions of GABAergic synapses is the ionic driving force for the chloride-permeable GABAA receptor (GABAAR). Here we review some of the sophisticated ways in which this ionic driving force can vary within neuronal circuits. This driving force for GABAARs is subject to tight spatial control, with the distribution of Cl− transporter proteins and channels generating regional variation in the strength of GABAAR signalling across a single neuron. GABAAR dynamics can result from short-term changes in their driving force, which involve the temporary accumulation or depletion of intracellular Cl−. In addition, activity-dependent changes in the expression and function of Cl− regulating proteins can result in long-term shifts in the driving force for GABAARs. The multifaceted regulation of the ionic driving force for GABAARs has wide ranging implications for mature brain function, neural circuit development, and disease

Neuroendocrine signaling modulates specific neural networks relevant to migraine

Migraine is a disabling brain disorder involving abnormal trigeminovascular activation and sensitization. Fasting or skipping meals is considered a migraine trigger and altered fasting glucose and insulin levels have been observed in migraineurs. Therefore peptides involved in appetite and glucose regulation including insulin, glucagon and leptin could potentially influence migraine neurobiology. We aimed to determine the effect of insulin (10 U·kg(− 1)), glucagon (100 μg·200 μl(− 1)) and leptin (0.3, 1 and 3 mg·kg(− 1)) signaling on trigeminovascular nociceptive processing at the level of the trigeminocervical-complex and hypothalamus. Male rats were anesthetized and prepared for craniovascular stimulation. In vivo electrophysiology was used to determine changes in trigeminocervical neuronal responses to dural electrical stimulation, and phosphorylated extracellular signal-regulated kinases 1 and 2 (pERK1/2) immunohistochemistry to determine trigeminocervical and hypothalamic neural activity; both in response to intravenous administration of insulin, glucagon, leptin or vehicle control in combination with blood glucose analysis. Blood glucose levels were significantly decreased by insulin (p < 0.001) and leptin (p < 0.01) whereas glucagon had the opposite effect (p < 0.001). Dural-evoked neuronal firing in the trigeminocervical-complex was significantly inhibited by insulin (p < 0.001), glucagon (p < 0.05) and leptin (p < 0.01). Trigeminocervical-complex pERK1/2 cell expression was significantly decreased by insulin and leptin (both p < 0.001), and increased by glucagon (p < 0.001), when compared to vehicle control. However, only leptin affected pERK1/2 expression in the hypothalamus, significantly decreasing pERK1/2 immunoreactive cell expression in the arcuate nucleus (p < 0.05). These findings demonstrate that insulin, glucagon and leptin can alter the transmission of trigeminal nociceptive inputs. A potential neurobiological link between migraine and impaired metabolic homeostasis may occur through disturbed glucose regulation and a transient hypothalamic dysfunction

Implications for migraine

Funding Information: The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: Margarida Martins-Oliveira is grateful to the Portuguese Fundação para a Ciência e Tecnologia (FCT) for its support with an individual PhD grant (SFRH/BD/77127/2011). The conduct of the research was financially supported by the EUROHEADPAIN European Union FP7 (PJG & PRH: 602633), the Wellcome Trust (PJG: 104033) and the Medical Research Council (PRH: MR/P006264/1). Publisher Copyright: © International Headache Society 2022.Background: Imaging migraine premonitory studies show increased midbrain activation consistent with the ventral tegmental area, an area involved in pain modulation and hedonic feeding. We investigated ventral tegmental area pharmacological modulation effects on trigeminovascular processing and consequent glycemic levels, which could be involved in appetite changes in susceptible migraine patients. Methods: Serotonin and pituitary adenylate cyclase-activating polypeptide receptors immunohistochemistry was performed in ventral tegmental area parabrachial pigmented nucleus of male Sprague Dawley rats. In vivo trigeminocervical complex neuronal responses to dura mater nociceptive electrical stimulation, and facial mechanical stimulation of the ophthalmic dermatome were recorded. Changes in trigeminocervical complex responses following ventral tegmental area parabrachial pigmented nucleus microinjection of glutamate, bicuculline, naratriptan, pituitary adenylate cyclase-activating polypeptide-38 and quinpirole were measured, and blood glucose levels assessed pre- and post-microinjection. Results: Glutamatergic stimulation of ventral tegmental area parabrachial pigmented nucleus neurons reduced nociceptive and spontaneous trigeminocervical complex neuronal firing. Naratriptan, pituitary adenylate cyclase-activating polypeptide-38 and quinpirole inhibited trigeminovascular spontaneous activity, and trigeminocervical complex neuronal responses to dural-evoked electrical and mechanical noxious stimulation. Trigeminovascular sensory processing through modulation of the ventral tegmental area parabrachial pigmented nucleus resulted in reduced circulating glucose levels. Conclusion: Pharmacological modulation of ventral tegmental area parabrachial pigmented nucleus neurons elicits changes in trigeminovascular sensory processing. The interplay between ventral tegmental area parabrachial pigmented nucleus activity and the sensory processing by the trigeminovascular system may be relevant to understand associated sensory and homeostatic symptoms in susceptible migraine patients.publishersversioninpres

Disorder strength and field-driven ground state domain formation in artificial spin ice: experiment, simulation and theory

Quenched disorder affects how non-equilibrium systems respond to driving. In the context of artificial spin ice, an athermal system comprised of geometrically frustrated classical Ising spins with a two-fold degenerate ground state, we give experimental and numerical evidence of how such disorder washes out edge effects, and provide an estimate of disorder strength in the experimental system. We prove analytically that a sequence of applied fields with fixed amplitude is unable to drive the system to its ground state from a saturated state. These results should be relevant for other systems where disorder does not change the nature of the ground state.Comment: The manuscript has been reworked. To be published in Phys. Rev. Let

On thermalization of magnetic nano-arrays at fabrication

We propose a model to predict and control the statistical ensemble of magnetic degrees of freedom in Artificial Spin Ice (ASI) during thermalized adiabatic growth. We predict that as-grown arrays are controlled by the temperature at fabrication and by their lattice constant, and that they can be described by an effective temperature. If the geometry is conducive to a phase transition, then the lowest temperature phase is accessed in arrays of lattice constant smaller than a critical value, which depends on the temperature at deposition. Alternatively, for arrays of equal lattice constant, there is a temperature threshold at deposition and the lowest temperature phase is accessed for fabrication temperatures {\it larger rather than smaller} than this temperature threshold. Finally we show how to define and control the effective temperature of the as-grown array and how to measure critical exponents directly. We discuss the role of kinetics at the critical point, and applications to experiments, in particular to as-grown thermalized square ASI, and to magnetic monopole crystallization in as-grown honeycomb ASI.Comment: 14 pages, 2 figures. A theoretical approach to experimental results reported in: Morgan J P, Stein A, Langridge S and Marrows C (2010) Nature Physics 7 7

Quantum control of 88^{88}Sr+^+ in a miniature linear Paul trap

We report on the construction and characterization of an apparatus for quantum information experiments using $^{88}$Sr$^+$ ions. A miniature linear radio-frequency (rf) Paul trap was designed and built. Trap frequencies above 1 MHz in all directions are obtained with 50 V on the trap end-caps and less than 1 W of rf power. We encode a quantum bit (qubit) in the two spin states of the $S_{1/2}$ electronic ground-state of the ion. We constructed all the necessary laser sources for laser cooling and full coherent manipulation of the ions' external and internal states. Oscillating magnetic fields are used for coherent spin rotations. High-fidelity readout as well as a coherence time of 2.5 ms are demonstrated. Following resolved sideband cooling the average axial vibrational quanta of a single trapped ion is $\bar n=0.05$ and a heating rate of $\dot{\bar n}=0.016$ ms$^{-1}$ is measured.Comment: 8 pages,9 figure