343 research outputs found
Metabotropic glutamate receptors as targets for novel anxiolytics
No full textAnxiety disorders are highly prevalent psychiatric illnesses posing an important social and economic burden. Their current pharmacotherapy shows short term efficacy, though nearly one third of patients do not achieve sustained remission. There is, therefore, a strong medical need for new therapeutic agents acting through novel mechanisms of action. Considerable work has focused on metabotropic glutamate (mGlu) receptors as potential targets for novel anxiolytics. Ligands acting at mGlu receptors showed promising results in preclinical studies, whereas their efficacy was dubious in clinical trials. Recent preclinical and clinical studies have opened new prospects for targeting mGlu receptors to treat anxiety disorders. This review provides an outlook on these progresses
On the existence of infinite, non-trivial F-sets
No full textIn this paper we prove a conjecture of J. Andrade, S.J. Miller, K. Pratt and M. Trinh, showing the existence of a non-trivial infinite F-set over Fq[x] for every fixed q. We also provide the proof of a refinement of the conjecture, involving the notion of width of an F-set, which is a natural number encoding the complexity of the set
The set of stable primes for polynomial sequences with large Galois group
No full textLet K be a number field with ring of integers OK, and let {fk}k∈N be a sequence of monic polynomials in OK[x] such that for every n ∈ N, the composition f(n) = f1 ◦ f2 ◦ ... ◦ fn is irreducible. In this paper we show that if the size of the Galois group of f(n) is large enough (in a precise sense) as a function of n, then the set of primes p ⊆ OK such that every f(n) is irreducible modulo p has density zero. Moreover, we prove that the subset of polynomial sequences such that the Galois group of f(n) is large enough has density 1, in an appropriate sense, within the set of all polynomial sequences
Functional expression of the GABA A receptor α2 and α3 subunits at synapses between intercalated medial paracapsular neurons of mouse amygdala
No full textIn the amygdala, GABAergic neurons in the intercalated medial paracapsular cluster (Imp) have been suggested to play a key role in fear learning and extinction. These neurons project to the central (CE) amygdaloid nucleus and to other areas within and outside the amygdala. In addition, they give rise to local collaterals that innervate other neurons in the Imp. Several drugs, including benzodiazepines (BZ), are allosteric modulators of GABA A receptors. BZ has both anxiolytic and sedative actions, which are mediated through GABA A receptors containing α2/α3 and α1 subunits, respectively. To establish whether α1 or α2/α3 subunits are expressed at Imp cell synapses, we used paired recordings of anatomically identified Imp neurons and high resolution immunocytochemistry in the mouse. We observed that a selective α3 subunit agonist, TP003 (100 nM), significantly increased the decay time constant of the unitary IPSCs. A similar effect was also induced by zolpidem (10 μM) or by diazepam (1 μM). In contrast, lower doses of zolpidem (0.1-1 μM) did not significantly alter the kinetics of the unitary IPSCs. Accordingly, immunocytochemical experiments established that the α2 and α3, but not the α1 subunits of the GABA A receptors, were present at Imp cell synapses of the mouse amygdala. These results define, for the first time, some of the functional GABA A receptor subunits expressed at synapses of Imp cells. The data also provide an additional rationale to prompt the search of GABA A receptor α3 selective ligands as improved anxiolytic drugs. © 2012 Geracitano, Fischer, Kasugai, Ferraguti and Capogna
A survey on abelian dynamical Galois groups
No full textLet be a number field, and . A recent conjecture
of Andrews and Petsche predicts that the dynamical Galois group of the pair
is abelian if and only if the pair is
-conjugated to , where is a power or a Chebyshev
map and is or , respectively, and is
a root of unity. We review three completely different approaches that allow to
prove several cases of the conjecture.Comment: Rendiconti Sem. Mat. Univ. Pol. Torino Vol. 80, 2022 (2022), 41 - 5
Subpopulations of neurokinin 1 receptor-expressing neurons in the rat lateral amygdala display a differential pattern of innervation from distinct glutamatergic afferents
No full textAbstractSubstance P by acting on its preferred receptor neurokinin 1 (NK1) in the amygdala appears to be critically involved in the modulation of fear and anxiety. The present study was undertaken to identify neurochemically specific subpopulations of neuron expressing NK1 receptors in the lateral amygdaloid nucleus (LA), a key site for regulating these behaviors. We also analyzed the sources of glutamatergic inputs to these neurons. Immunofluorescence analysis of the co-expression of NK1 with calcium binding proteins in LA revealed that ∼35% of NK1-containing neurons co-expressed parvalbumin (PV), whereas no co-localization was detected in the basal amygdaloid nucleus. We also show that neurons expressing NK1 receptors in LA did not contain detectable levels of calcium/calmodulin kinase IIα, thus suggesting that NK1 receptors are expressed by interneurons. By using a dual immunoperoxidase/immunogold-silver procedure at the ultrastructural level, we found that in LA ∼75% of glutamatergic synapses onto NK1-expressing neurons were labeled for the vesicular glutamate transporter 1 indicating that they most likely are of cortical, hippocampal, or intrinsic origin. The remaining ∼25% were immunoreactive for the vesicular glutamate transporter 2 (VGluT2), and may then originate from subcortical areas. On the other hand, we could not detect VGluT2-containing inputs onto NK1/PV immunopositive neurons. Our data add to previous localization studies by describing an unexpected variation between LA and basal nucleus of the amygdala (BA) in the neurochemical phenotype of NK1-expressing neurons and reveal the relative source of glutamatergic inputs that may activate these neurons, which in turn regulate fear and anxiety responses
Metabotropic glutamate receptors
No full textMetabotropic glutamate receptors (mGlus) are a family of G-protein-coupled receptors activated by the neurotransmitter glutamate. Molecular cloning has revealed eight different subtypes (mGlu1-8) with distinct molecular and pharmacological properties. Multiplicity in this receptor family is further generated through alternative splicing. mGlus activate a multitude of signalling pathways important for modulating neuronal excitability, synaptic plasticity and feedback regulation of neurotransmitter release. In this review, we summarize anatomical findings (from our work and that of other laboratories) describing their distribution in the central nervous system. Recent evidence regarding the localization of these receptors in peripheral tissues will also be examined. The distinct regional, cellular and subcellular distribution of mGlus in the brain will be discussed in view of their relationship to neurotransmitter release sites and of possible functional implications. © Springer-Verlag 2006
Energy optimization for a robust and flexible interaction control
No full textThe possibility of adapting online the way a robot interacts with the environment is becoming more and more important. In this paper we introduce the tank based admittance controller. We show that all the admittance controllers can be modeled as an energy optimization problem and then we introduce a novel admittance control strategy that allows to change online the interactive behavior while preserving a stable interaction with the environment. The effectiveness of the proposed architecture is experimentally validated
Kasugai et al Neuron 2019 D-16-02077R1
No full textAssociative learning is thought to involve different forms of activity-dependent synaptic plasticity. While previous studies have mostly focused on learning-related changes occurring at excitatory glutamatergic synapses, we found that associative learning such as fear conditioning also entails long-lasting functional and structural plasticity of GABAergic synapses onto pyramidal neurons of the murine basal amygdala. Fear conditioning-mediated structural remodeling of GABAergic synapses was associated with a change in mIPSC kinetics and an increase in the fraction of synaptic benzodiazepine-sensitive (BZD) GABAA receptors containing the α2 subunit, without altering the intrasynaptic distribution and overall amount of BZD-GABAA receptors. These structural and functional synaptic changes were partly reversed by extinction training. These findings provide evidence that associative learning, such as Pavlovian fear conditioning and extinction, sculpts inhibitory synapses to regulate inhibition of active neuronal networks, a process which may tune amygdala circuit responses to threat
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