SUMMARY
Neuronal oscillations in the rat hippocampus relate to both memory and locomotion, raising the question of how these cognitive and behavioral correlates interact to determine the oscillatory network state of this region. Here, rats freely locomoted while performing an object-location task designed to test hippocampus-dependent spatial associative memory. Rhythmic activity in theta, beta, slow gamma, and fast gamma frequency ranges were observed in both action potentials and local field potentials (LFPs) across four main hippocampal subregions. Several patterns of LFP oscillations corresponded to overt behavior (e.g., increased dentate gyrus-CA3 beta coherence during stationary moments and CA1-subiculum theta coherence during locomotion). In comparison, slow gamma (~40 Hz) oscillations throughout the hippocampus related most specifically to object-location associative memory encoding rather than overt behavior. The results help to untangle how hippocampal oscillations relate to both memory and motion, and single out slow gamma oscillations as a distinguishing correlate of spatial associative memory.
Acetylcholine signaling through muscarinic receptors has been shown to benefit memory performance in some conditions, but pan-muscarinic activation also frequently leads to peripheral side effects. Drug therapies that selectively target M1 or M4 muscarinic receptors could potentially improve memory while minimizing side effects mediated by the other muscarinic receptor subtypes. The ability of three recently developed drugs that selectively activate M1 or M4 receptors to improve recognition memory was tested by giving Long-Evans rats subcutaneous injections of three different doses of the M1 agonist VU0364572, the M1 positive allosteric modulator BQCA or the M4 positive allosteric modulator VU0152100 before performing an object recognition memory task. VU0364572 at 0.1 mg/kg, BQCA at 1.0 mg/kg and VU0152100 at 3.0 and 30.0 mg/kg improved the memory performance of rats that performed poorly at baseline, yet the improvements in memory performance were the most statistically robust for VU0152100 at 3.0 mg/kg. The results suggested that selective M1 and M4 receptor activation each improved memory but that the likelihood of obtaining behavioral efficacy at a given dose might vary between subjects even in healthy groups depending on baseline performance. These results also highlighted the potential of drug therapies that selectively target M1 or M4 receptors to improve memory performance in individuals with impaired memory.
The hormone human chorionic gonadotropin (hCG) serves to maintain the fetus during early pregnancy and regulate the onset of labor in late pregnancy. hCG also prevents Neisseria gonorrhoeae from developing invasive characteristics. Part of the beta subunit of hCG has an amino acid sequence similar to that of the hinge of human IgA1, which is the site of action of IgA1 proteases. This study examined the sensitivity of hCG to gonococcal IgA1 proteases, by means of autoradiography, immunoblotting, and RIA. hCG was cleaved in the beta subunit by the type 1 but not the type 2 IgA1 proteases of N. gonorrhoeae. hCG cleavage by gonococcal IgA1 proteases in vivo may increase the invasiveness of the pathogen and destroy its natural biologic activity, with major consequences for the fetus and the pregnancy.
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