Neuroscience
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Gonadal hormones are becoming increasingly recognized for their effects on cognition. Estrogens, in particular, have received attention for their effects on learning and memory that rely upon the functioning of various brain regions. However, the impacts of androgens on cognition are relatively under investigated. ⋯ We highlight the relevance of considering not only the actions of the most commonly studied steroids (i.e., testosterone, 17β-estradiol, and dihydrotestosterone), but also that of their metabolites and precursors, which interact with a plethora of different receptors and signalling molecules, ultimately modulating behaviour. We point out that it is also essential to investigate the effects of androgens, their precursors and metabolites in females, as prior studies have mostly focused on males. Overall, a comprehensive analysis of the impact of steroids such as androgens on behaviour is fundamental for a full understanding of the neural mechanisms underlying social cognition, including that of humans.
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MMG22 is a bivalent ligand containing MOR agonist and mGluR5 antagonist pharmacophores connected by a 22-atom linker. Intrathecal (i.t.) administration of MMG22 to inflamed mice has been reported to produce fmol-range antinociception in the reversal of LPS-induced hyperalgesia. MMG22 reduced hyperalgesia in the spared nerve injury (SNI) model of neuropathic pain at 10 days after injury but not at 30 days after injury, perhaps related to the inflammation that occurs early after injury but subsequently subsides. ⋯ We propose that MMG22 induces the formation of a MOR-mGluR5 heteromer through selective interaction with the upregulated NR2B subunit of activated NMDAR, in view of the 4600-fold reduction of i.t. MMG22 antinociception by the selective NR2B antagonist, Ro25-6981. A possible explanation for the substantially reduced potency for MMG22 in the SNI model is discussed.
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Previous work in the suprachiasmatic nucleus (SCN), the locus of the principal circadian clock, has shown that the activation state of the ERK/MAPK effector p90 ribosomal S6 kinase (RSK) is responsive to photic stimulation and is modulated across the circadian cycle. These data raise the prospect that RSK signaling contributes to both SCN clock timing and entrainment. Here, we found marked expression of the three main RSK isoforms (RSK1/2/3) within the SCN of C57/Bl6 mice. ⋯ To test the potential contribution of RSK signaling to SCN pacemaker activity, slice cultures from a per1-Venus circadian reporter mouse line were chronically treated with SL0101. Suppression of RSK signaling led to a significant lengthening of the circadian period (∼40 min), relative to vehicle-treated slices. Together, these data reveal that RSK functions as a signaling intermediate that regulates light-evoked clock entrainment and the inherent time keeping properties of the SCN.
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We accurately sense locations of objects touching various points on the body and, if they are irritants, make accurate rapid movements to remove them. Such movements require accurate proprioception of orientation and motion of the reaching limb and of the target. However, it is unknown whether acuity of these sensations is similar for different points on the body. ⋯ Mean errors for reaches to touch points on the left lower limb were least accurate (p < 0.05), with mean errors averaging 1.5-3.1 cm relative to movements made with vision. We conclude that there is high proprioceptive acuity for locations of points on axial structures and the left upper limb including the digits, which contrasts with previous reports of greatly distorted proprioceptive maps of the face/head and hand. Apparently low proprioceptive acuity for points on the leg may be task sensitive as many lower limb motor tasks can be performed accurately without vision.
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Targeting reconsolidation with propranolol, a blocker of β-adrenergic receptors (β-ARs), emerged as a potential treatment for maladaptive memories such as those involved in posttraumatic stress disorder (PTSD). Reconsolidation targeting treatments for PTSD are becoming a common practice in the clinic and it is important to unveil any side effects upon 'non-targeted' memories. While previous studies have focused on propranolol's effects on the reconsolidation of emotional/distressful memories, the present study asked whether propranolol is involved in the reconsolidation of recognition memories - by assessing its effects on distinct memory components and the role of the dorsal hippocampus. ⋯ Propranolol infusions consistently impaired the addition of novel information to the previously consolidated memory trace regardless of dose, and the retention of familiar objects was not affected. Higher doses of propranolol also hindered memory of a familiar object that was not presented during the reactivation session, but was previously placed at the same location where novel information was presented during reactivation. The present results shed light on the role of β-ARs on the reconsolidation of different memory components and argue for the need for further studies examining possible recognition memory deficits following propranolol treatment.