Neuroscience
-
Growing research indicates oxytocin may be involved in relieving anxiety and attenuating the rewarding effects of psychostimulants. This study investigated the effects of subchronic oxytocin treatments on mesolimbic dopamine transmission in areas associated with anxiety and addiction, the amygdala and the nucleus accumbens (NAc), respectively. Using in vivo fixed potential amperometry, stimulation-evoked dopamine release was recorded in anesthetized mice pretreated with subchronic oxytocin (four i.p. injections of 1 mg/kg oxytocin or saline with 48 h between injections). ⋯ Furthermore, oxytocin pretreated mice displayed a reduced dopaminergic response to the drug challenge of nomifensine relative to control mice. Together these results suggest that oxytocin may be useful at treating aspects of anxiety and drug abuse. Elucidating the neural effects of oxytocin is critical given the multitude of potential therapeutic uses for this drug.
-
Neurogenesis in the substantia nigra (SN) has been a controversial issue. Here we report that neurogenesis can be induced in the adult rodent SN by transplantation of embryoid body cells (EBCs) derived from mouse embryonic stem cells. The detection of Sox2+ dividing (BrdU+) putative host neural precursor cells (NPCs) between 1 and 6 days post-transplantation (dpt) supported the neurogenic capacity of the adult SN. ⋯ Remarkably, new blood vessels formed in association with the neurogenic process that, when precluded, caused a reduction in neuroblast production. Accordingly, two proteins secreted by EBCs, Fgf2 and Vegf, were able to promote the emergence of Dcx+/Psa-Ncam+, Tubb3+ and NeuN+/BrdU+ cells in vivo in the absence of EBCs. We propose that the adult SN is a mostly silent neurogenic niche with the ability to generate new neurons by typical and atypical mechanisms.
-
Malformations of cortical development (MCDs) include many different Central Nervous System (CNS) disorders related to a complex process of cortex formation. In children with refractory epilepsy to drug treatment undergoing surgery, focal cortical dysplasia (FCD), one of the MCDs, is considered the most common structural brain lesion found. This study aimed to study the possible alterations in neural differentiation process of human induced pluripotent stem cells (hiPSCs) related to migration and synaptic aspects from fibroblasts of two individuals affected by FCD type IIb (45-year-old male and 12-year-old female) and normal individuals. ⋯ Our results showed that in all processes and groups, individuals with dysplasia presented alterations in most part of the genes in relation to control individuals. According to our results, it is suggested that the different expressions are mainly involved in alterations of the expression of receptors and capture sites, timing, coupling of synaptic vesicles with the presynaptic membrane, regulation of ion channel and synaptic exocytosis, imbalance of the apoptosis process and abnormal microtubules that may also contribute to delays in synaptogenesis. Thus, brain formation with dysplasia is probably influenced by these genes studied.
-
Human studies have repeatedly shown that conditioning pain modulation (CPM) exerts an overall descending inhibitory effect over spinal nociceptive activity. Previous studies have reported a reduction of the nociceptive withdrawal reflex (NWR) under CPM. Still, how descending control influences the muscle activation patterns involved in this protective behavior remains unknown. ⋯ Under CPM, Module I activation amplitude was significantly reduced in a narrow time-window interval (118-156 ms) mainly affecting distal muscles, whereas Module II activation amplitude was significantly reduced in a wider time-window interval (150-250 ms), predominantly affecting proximal muscles. These findings suggest that proximal muscles are largely under supraspinal control. The descending inhibitory drive exerted onto the spinal cord may adjust the withdrawal pattern by differential recruitment of the muscles involved in the protective behavior.
-
μ-Opioid Receptor Activation Directly Modulates Intrinsically Photosensitive Retinal Ganglion Cells.
Intrinsically photosensitive retinal ganglion cells (ipRGCs) encode light intensity and trigger reflexive responses to changes in environmental illumination. In addition to functioning as photoreceptors, ipRGCs are post-synaptic neurons in the inner retina, and there is increasing evidence that their output can be influenced by retinal neuromodulators. Here we show that opioids can modulate light-evoked ipRGC signaling, and we demonstrate that the M1, M2 and M3 types of ipRGCs are immunoreactive for μ-opioid receptors (MORs) in both mouse and rat. ⋯ Recordings from solitary ipRGCs, enzymatically dissociated from retinas obtained from melanopsin-driven fluorescent reporter mice, confirmed that DAMGO exerts its effect directly through MORs expressed by ipRGCs. Reduced ipRGC excitability occurred via modulation of voltage-gated potassium and calcium currents. These findings suggest a potential new role for endogenous opioids in the mammalian retina and identify a novel site of action-MORs on ipRGCs-through which opioids might exert effects on reflexive responses to environmental light.