Neuroscience
-
Acquired information is stabilized into long-term memory through a process known as consolidation. Though, after consolidation, when stored information is retrieved they can be again susceptible, allowing modification, updating and strengthening and to be re-stabilized they need a new process referred to as memory reconsolidation. However, the molecular mechanisms of recognition memory consolidation and reconsolidation are not fully understood. ⋯ We verified that the blockade of AMPA receptors (AMPAr) and L-VDCCs calcium channels impaired ORM consolidation and reconsolidation when administered into CA1 immediately after sample phase or reactivation phase and that these impairments were blocked by the administration of AMPAr agonist and of neurotrophin BDNF. Also, the blockade of CaMKII impaired ORM consolidation when administered 3 h after sample phase but had no effect on ORM reconsolidation and its effect was blocked by the administration of BDNF, but not of AMPAr agonist. So, this study provides new evidence of the molecular mechanisms involved on the consolidation and reconsolidation of ORM, demonstrating that AMPAr and L-VDCCs are necessary for the consolidation and reconsolidation of ORM while CaMKII is necessary only for the consolidation and also that there is a link between BDNF and AMPAr, L-VDCCs and CaMKII as well as a link between AMPAr and L-VDCCs on ORM consolidation and reconsolidation.
-
Fetal alcohol spectrum disorders (FASD) constitute a prevalent, yet preventable, developmental disorder worldwide. While a wealth of research demonstrates that altered function of hippocampus (HPC) and prefrontal cortex may underlie behavioral impairments in FASD, only one published paper to date has examined the impact of developmental alcohol exposure (AE) on the region responsible for coordinated prefrontal-hippocampal activity: thalamic nucleus reuniens (Re). In the current study, we used a rodent model of human third trimester AE to examine both the acute and lasting impact of a single-day AE on Re. ⋯ This relationship between short-term cell death versus cell number suggests that alcohol-related cell loss is driven by induction of apoptosis. In adulthood, alcohol-exposed animals displayed permanent cell loss (mediating volume loss in the Re), which included a reduction in neuron number (relative to procedural controls). Both procedural controls and alcohol exposed animals displayed a deficit in non-neuronal cell number relative to typically-developing controls, suggesting that Re cell populations may be vulnerable to early life stress as well as AE in an insult- and cell type-dependent manner.
-
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that selectively affects upper and lower motoneurons. Dismantlement of the neuromuscular junction (NMJ) is an early pathological hallmark of the disease whose cellular origin remains still debated. We developed an in vitro NMJ model to investigate the differential contribution of motoneurons and muscle cells expressing ALS-causing mutation in the superoxide dismutase 1 (SOD1) to neuromuscular dysfunction. ⋯ Expression of SOD1G93A in myotubes does not prevent the formation of a functional NMJ but leads to decreased contraction frequency and lowers the slow type I MHC isoform transcript levels. Expression of SOD1G93A in both motoneurons and myotubes or in motoneurons alone however alters the formation of a functional NMJ. Our results strongly suggest that motoneurons are a major factor involved in the process of NMJ dismantlement in an experimental model of ALS.
-
Plexin family proteins mediate semaphorin signalling during dendritic arbour development. However, the role of PlexinA3 in the growth of dendrites of cultured cerebellar granule neurons (CGNs) is not known. We found that PlexinA3 colocalizes with CRMP2 (collapsin response mediator protein 2) in dendritic shafts. ⋯ These increases were enhanced with CRMP2 overexpression and abolished with CRMP2 knockdown, indicating that CRMP2 is the downstream effector. Furthermore, PlexinA3/CRMP2 signalling contributed to Sema3A-controlled dendritic growth. Together, these data identify a novel PlexinA3/CRMP2 pathway in semaphorin-regulated growth of cultured CGN dendrites.
-
During neural network development, growing axons read a map of guidance cues expressed in the surrounding tissue that lead the axons toward their targets. In particular, Xenopus retinal ganglion axons use the cues Slit1 and Semaphorin 3a (Sema3a) at a key guidance decision point in the mid-diencephalon in order to continue on to their midbrain target, the optic tectum. The mechanisms that control the expression of these cues, however, are poorly understood. ⋯ The Lhx2-VP16 constitutive activator fusion reduces sema3a promoter function, and the Lhx2-En constitutive repressor fusion increases slit1 induction. In contrast, etv1 gain of function transactivates both guidance genes in vitro and in the forebrain. Based on these data, together with our previous work, we hypothesize that Fgf signalling promotes both slit1 and sema3a expression in the forebrain through Etv1, while using Lhx2/9 to limit the extent of expression, thereby establishing the proper boundaries of guidance cue expression.