Opposite Effects of mGluR1a and mGluR5 Activation on Nucleus Accumbens Medium Spiny Neuron Dendritic Spine Density.

The group I metabotropic glutamate receptors (mGluR1a and mGluR5) are important modulators of neuronal structure and function. Although these receptors share common signaling pathways, they are capable of having distinct effects on cellular plasticity. We investigated the individual effects of mGluR1a or mGluR5 activation on dendritic spine density in medium spiny neurons in the nucleus accumbens (NAc), which has become relevant with the potential use of group I mGluR based therapeutics in the treatment of drug addiction. We found that systemic administration of mGluR subtype-specific positive allosteric modulators had opposite effects on dendritic spine densities. Specifically, mGluR5 positive modulation decreased dendritic spine densities in the NAc shell and core, but was without effect in the dorsal striatum, whereas increased spine densities in the NAc were observed with mGluR1a positive modulation. Additionally, direct activation of mGluR5 via CHPG administration into the NAc also decreased the density of dendritic spines. These data provide insight on the ability of group I mGluRs to induce structural plasticity in the NAc and demonstrate that the group I mGluRs are capable of producing not just distinct, but opposing, effects on dendritic spine density

Representative images of DiI-labeled neuron and dendritic segment.

<p>(A) Low power magnification of a DiI-labeled medium spiny neuron, <i>scale bar</i> 50 μm. (B) High power magnification of a reconstructed dendritic segment from a medium spiny neuron, <i>scale bar</i> 5 μm.</p

Positive modulation of mGluR1a increases spine density in the nucleus accumbens but not in the dorsal striatum.

<p>(A) Twenty-four hours after systemic administration, SYN119 (10 mg/kg, <i>n</i> = 10 animals) increased dendritic spine density compared to vehicle control (<i>n</i> = 9) in the nucleus accumbens core but had no effect on spine length or head diameter. (B) SYN119 also decreased spine density in the nucleus accumbens shell and did not affect spine length or head diameter. *<i>p</i> < 0.05.</p

Activation of mGluR5 site-specifically decreases spine density in the nucleus accumbens.

<p>(A) Schematic representation of injection sites of either vehicle (open circles) or CHPG (filled circles). Numbers represent distance from bregma, based on the atlas of Paxinos and Watson [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0162755#pone.0162755.ref016" target="_blank">16</a>]. (B)Twenty-four hours after local microinfusion to the nucleus accumbens, CHPG (10 μg/side, <i>n</i> = 7 animals) decreased dendritic spine density compared to vehicle control (<i>n</i> = 7) in the nucleus accumbens core but had no effect on spine length or head diameter. (B) CHPG also decreased spine density in the nucleus accumbens shell and did not affect spine length or head diameter. *<i>p</i> < 0.05.</p

Improving constraints on the extended mass distribution in the Galactic Center with stellar orbits

International audienceStudying the orbital motion of stars around Sagittarius A* in the Galactic Center provides a unique opportunity to probe the gravitational potential near the supermassive black hole at the heart of our Galaxy. Interferometric data obtained with the GRAVITY instrument at the Very Large Telescope Interferometer (VLTI) since 2016 has allowed us to achieve unprecedented precision in tracking the orbits of these stars. GRAVITY data have been key to detecting the in-plane, prograde Schwarzschild precession of the orbit of the star S2, as predicted by General Relativity. By combining astrometric and spectroscopic data from multiple stars, including S2, S29, S38, and S55 - for which we have data around their time of pericenter passage with GRAVITY - we can now strengthen the significance of this detection to an approximately $10 \sigma$ confidence level. The prograde precession of S2's orbit provides valuable insights into the potential presence of an extended mass distribution surrounding Sagittarius A*, which could consist of a dynamically relaxed stellar cusp comprised of old stars and stellar remnants, along with a possible dark matter spike. Our analysis, based on two plausible density profiles - a power-law and a Plummer profile - constrains the enclosed mass within the orbit of S2 to be consistent with zero, establishing an upper limit of approximately $1200 \, M_\odot$ with a $1 \sigma$ confidence level. This significantly improves our constraints on the mass distribution in the Galactic Center. Our upper limit is very close to the expected value from numerical simulations for a stellar cusp in the Galactic Center, leaving little room for a significant enhancement of dark matter density near Sagittarius A*