Neuroscience
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Motor learning depends on plastic reorganization of neural networks within the primary motor cortex (M1). In the circuitry of M1, integration and processing of afferent inputs is executed by pyramidal neurons of layer II/III. Thus, an involvement of these layer II/III pyramids in learning-induced changes is highly plausible. ⋯ Spine density increased in apical and basal dendrites of both superficial and deep layer II/III neurons, likely an effect of ageing that occurred independently from motor learning. This increase in spine density was accompanied with a morphological change towards stubby- and mushroom-like spines. Thus, profound but delayed changes occurred within the dendritic compartment of layer II/III pyramidal cells.
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Early gestation is a neurodevelopmental period that is especially vulnerable to environmental insult and one in which neurogenesis features prominently. Prenatal perturbation during early gestation has been linked to neuropsychiatric illnesses such as autism and schizophrenia, and severe environmental insult during this period can result in profound mental impairment. Midbrain dopamine neurons are generated during early gestation and play a key role in the motor, cognitive and reward circuitries implicated in neuropsychiatric disease and addiction. ⋯ Mean total neuron number in the irradiated monkeys was significantly reduced on average by 33% compared to that of the control group. Somal size did not differ between the groups, suggesting that the integrity of survivor populations was not impacted. Reduced midbrain dopamine neuron number in fetally irradiated, adult monkeys indicates that radiation exposure during the critical period of neurogenesis results in an enduring reduction of this population and underscores the susceptibility of early neurodevelopmental processes to irreversible damage from environmental exposures.
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Large conductance of Ca2+-activated K+ channel (KCa1.1) plays an inhibitory role in neuroexcitation. However, the expression of KCNMB4/β4-subunit in the nodose ganglia (NG) and nucleus tractus solitarius (NTS), and its effect and regulation on baroreflex afferent function at post-transcriptional level of female rats remains unknown. Here, we demonstrated that the expression of β4-subunit encoded by KCNMB4 was significantly lower in females vs. males and ovariectomized (OVX) rats in the NG. ⋯ In consistent, an inverse expression pattern between miR-504 and KCNMB4 was observed in baroreflex afferents. The paxilline-sensitive β4-subunits is less in Ah-types and up-regulated by ovariectomy. These data indicated that KCa1.1 β4-subunit is the key regulator in neuroexcitation of Ah-types and sexual-dimorphism in baroreflex afferent function through estrogen-dependent inhibition of KCNMB4 expression via miR-504.
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A goal in addiction research is to distinguish forms of neuroplasticity that are involved in the transition to addiction from those involved in mere drug taking. Animal models of drug self-administration are essential in this context. Here, we compared in male rats two cocaine self-administration procedures that differ in the extent to which they evoke addiction-like behaviours. ⋯ Compared to LgA-90 s rats, IntA-5 s rats had more cocaine-induced c-fos mRNA in the orbitofrontal and prelimbic cortices and the caudate-putamen. Thus, a cocaine self-administration procedure (intermittent intake of rapid infusions) that promotes increased incentive motivation for the drug also enhances cocaine-induced gene regulation in corticostriatal regions. This suggests that increased drug-induced recruitment of these regions could contribute to the neural and behavioural plasticity underlying the transition to addiction.
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Aberrant depressive-like behaviors in olfactory bulbectomized (OBX) mice have been documented by previous studies. Here, we show that memantine enhances adult neurogenesis in the subgranular zone of the hippocampal dentate gyrus (DG) and improves depressive-like behaviors via inhibition of the ATP-sensitive potassium (KATP) channel in OBX mice. Treatment with memantine (1-3 mg/kg; per os (p.o.)) for 14 days significantly improved depressive-like behaviors in OBX mice, as assessed using the tail-suspension and forced-swim tests. ⋯ In contrast, both the improvement of depressive-like behaviors and increase in BrdU-positive neurons in the DG following treatment with memantine were unapparent in OBX-treated Kir6.1 heterozygous (+/-) mice but not OBX-treated Kir6.2 heterozygous (+/-) mice. Furthermore, the increase in CaMKIV (Thr-196) and Akt (Ser-473) phosphorylation and BDNF protein expression levels was not observed in OBX-treated Kir6.1 +/- mice. Overall, our study shows that memantine improves OBX-induced depressive-like behaviors by increasing adult neurogenesis in the DG via Kir6.1 channel inhibition.