European Journal of Neuroscience最新文献

Regulator of G protein signalling 14 (RGS14) is a multifunctional signalling protein that serves as a natural suppressor of synaptic plasticity in the mouse brain. Our previous studies showed that RGS14 is highly expressed in postsynaptic dendrites and spines of pyramidal neurons in hippocampal area CA2 of the developing mouse brain. However, our more recent work with monkey brain shows that RGS14 is found in multiple neuron populations throughout hippocampal area CA1 and CA2, caudate nucleus, putamen, globus pallidus, substantia nigra and amygdala. In the mouse brain, we also have observed RGS14 protein in discrete limbic regions linked to reward behaviour and addiction, including the central amygdala and the nucleus accumbens, but a comprehensive mapping of RGS14 protein expression in the adult mouse brain is lacking. Here, we report that RGS14 is more broadly expressed in mouse brain than previously known. Intense RGS14 staining is observed in specific neuron populations of the hippocampal formation, amygdala, septum, bed nucleus of stria terminalis and ventral striatum/nucleus accumbens. RGS14 is also observed in axon fibre tracts including the dorsal fornix, fimbria, stria terminalis and the ventrohippocampal commissure. Moderate RGS14 staining is observed in various other adjacent regions not previously reported. These findings show that RGS14 is expressed in brain regions that govern aspects of core cognitive functions such as sensory perception, emotion, memory, motivation and execution of actions and suggest that RGS14 may serve to suppress plasticity and filter inputs in these brain regions to set the overall tone on experience-to-action processes.

The suprachiasmatic nucleus is the circadian pacemaker of the mammalian brain. Suprachiasmatic nucleus neurons display synchronization of their firing frequency on a circadian timescale, which is required for the pacemaker function of the suprachiasmatic nucleus. However, the mechanisms by which suprachiasmatic nucleus neurons remain synchronized in vivo are poorly understood, although synaptic communication is considered indispensable. Suprachiasmatic nucleus neurons contain the neurotransmitter GABA and express GABA receptors. This has inspired the hypothesis that GABA signalling may play a central role in network synchronization, although this remains untested in vivo. Here, using local genetic deletion, we show that disruption of GABA synaptic transmission within the suprachiasmatic nucleus of adult mice results in the eventual deterioration of physiological and behavioural rhythmicity in vivo and concomitant cellular desynchrony in vitro. These findings suggest that intercellular GABA signalling is essential for behavioural rhythmicity and cellular synchrony of the suprachiasmatic nucleus neural network.

Concentric and eccentric contractions show different patterns of neural activity at both peripheral and cortical levels, which are thought to influence the perception of action properties such as the weight of objects moved by others. The aim of this study was to investigate how the type of muscle contraction influences weight estimation during action observation. Forty-eight volunteers completed the Main experiment and the Control experiment. In the Main experiment, they performed a weight discrimination video task in which they watched videos of an actor moving two objects, a comparison, and a reference box, executing concentric or eccentric contractions and they had to indicate which box was the heaviest. Sensitivity analysis and psychometric functions were used to analyse the data. In the Control experiment, observers judged the actor's effort in moving the boxes. The results of the Main experiment showed that the weight discrimination sensitivity was higher in the eccentric condition for the light boxes. Conversely, for the heaviest boxes, discrimination sensitivity was higher in the concentric condition. These results were confirmed by the psychometric function analysis. The control experiment showed that the perceived difference in effort between the comparison and reference stimuli was greater in the eccentric than in the concentric condition for light stimuli. These results showed that the ability to evaluate the weight of the object involved in the observed action was influenced by the type of contraction and the amount of weight. The effort attributed to the actor influenced the observer's perception.

Individual neurons of the hypothalamic suprachiasmatic nuclei (SCN) contain an intracellular molecular clock that drives these neurons to exhibit day-night variation in excitability. The neuropeptide vasoactive intestinal polypeptide (VIP) and its cognate receptor, VPAC₂, are synthesized by SCN neurons and this intercellular VIP-VPAC₂ receptor signal facilitates coordination of SCN neuronal activity and timekeeping. How the loss of VPAC₂ receptor signalling affects the electrophysiological properties and states of SCN neurons as well as their responses to excitatory inputs is unclear. Here we used patch-clamp electrophysiology and made recordings of SCN neurons in brain slices prepared from transgenic animals that do not express VPAC₂ receptors (Vipr2^-/- mice) as well as animals that do (Vipr2^+/+ mice). We report that while Vipr2^+/+ neurons exhibit coordinated day-night variation in their electrical state, Vipr2^-/- neurons lack this and instead manifest a range of states during both day and night. Further, at the population level, Vipr2^+/+ neurons vary the membrane threshold potential at which they start to fire action potentials from day to night, while Vipr2^-/- neurons do not. We provide evidence that Vipr2^-/- neurons lack a component of voltage-gated sodium currents that contribute to SCN neuronal excitability. Moreover, we determine that this aberrant temporal control of neuronal state and excitability alters neuronal responses to a neurochemical mimic of the light-input pathway to the SCN. These results highlight the critical role VIP-VPAC₂ receptor signalling plays in the temporal expression of individual neuronal states as well as appropriate ensemble activity and input gating of the SCN neural network.

Reduced hippocampal volumes are a feature of many mental disorders. Childhood maltreatment is a known risk factor for the development of psychopathology and has consistently been linked to hippocampal volume reductions in adults, but not in children and adolescents. We propose that maltreatment-related difficulties in coping with developmental tasks in adolescence and young adulthood might underlie the delayed emergence of hippocampal volume reductions in maltreated individuals. In a study with 196 healthy young adults (mean age [years]: 24.0 ± 3.2, 50% female, 20.6% living with a partner (missings: n = 2)), we investigated the interaction between childhood maltreatment (Childhood Trauma Screener) and the breakup of a steady romantic relationship (List of Threatening Experiences Questionnaire) on hippocampal magnetic resonance imaging grey matter volumes. The experience of a romantic relationship breakup moderated the association between childhood maltreatment and bilateral hippocampal volumes, revealing more negative associations with hippocampal volumes in participants with at least one breakup compared to those with no breakup experience (right hippocampus: β = - 0.05 ± 0.02, p = 0.031, p (FDR) = 0.031; left hippocampus: β = -0.06 ± 0.02, p = 0.005, p (FDR) = 0.009). Moreover, our findings provide some evidence that childhood maltreatment is related to smaller bilateral hippocampal volumes only in those adults who suffered from a relationship breakup (right hippocampus: β = -0.23 ± 0.10, p = 0.018, p (FDR) = 0.018; left hippocampus: β = -0.24 ± 0.10, p = 0.016, p (FDR) = 0.018;). Our study highlights the interaction of adult social bonds with early adversity on vulnerability to psychopathology.

The low-density lipoprotein receptor (LDLr) is the first member of a closely related transmembrane protein family. It is known for its involvement in various physiological processes, mainly in the regulation of lipid metabolism, especially in the brains of mammals and zebrafish. In zebrafish, two ldlr genes (ldlra and b) have been identified and their distribution in the brain is not well documented. Recently, the roles of ldlr and its inhibitor pcsk9 in regenerative process after telencephalic brain injury have been discussed. In this study, we explored the expression patterns of these genes during zebrafish development. We found that ldlra expression was detected at the end of the pharyngula period (48 hpf) and increased during the larval stage. Conversely, ldlrb expression was observed from zygotic to larval stages. Using techniques like in situ hybridization and taking advantage of transgenic fish, we demonstrated the widespread distribution of ldlra, ldlrb and pcsk9 in the brain of adult zebrafish. Specifically, these genes were expressed in neurons and neural stem cells and also at lower levels in endothelial cells. As expected, intraperitoneal injection of fluorescent-labelled LDLs resulted in their uptake by cerebral endothelial cells in a homeostatic context, whereas they diffused within the brain parenchyma after telencephalic injury. However, after intracerebroventricular injections into animals, LDL particles were not taken up by neural stem cells. In conclusion, our results provide additional evidence for LDLr expression in the brain of adult zebrafish. These results raise the question of the role of LDLr in the cholesterol/lipid imbalance in cerebral complications.

The suprachiasmatic nucleus (SCN) is the master clock that directly dictates behavioural rhythms to anticipate the earth's light/dark cycles. Although post-transcriptional regulators called microRNAs have been implicated in physiological SCN function, how the absence of the entire mature miRNome impacts SCN output has not yet been explored. To study the behavioural consequences of miRNA depletion in the SCN, we first generated a mouse model in which Dicer is inactivated in the SCN by crossing Syt10^Cre mice with Dicer^flox mice to study behavioural consequences of miRNA depletion in the SCN. Loss of all mature miRNAs in the SCN shortened the circadian period length by ~37 minutes at the tissue level and by ~45 minutes at the locomotor activity level. Moreover, knockout animals exhibited a reduction in the precision of the circadian rhythm with more variable activity onsets under both LD 12:12 and DD conditions. We also observed that knockouts with higher onset variations were inclined to develop ultradian rhythms under constant light. In a second mouse model, recombination of Dicer^flox via Cre delivery specifically in the SCN resulted in loss of behavioural rhythms in some animals depending on the injection efficiency. Together, our observations highlight the importance of microRNAs for a physiological SCN function and their pivotal role in robust circadian oscillations.

Parkinson's disease (PD) is primarily characterized by three histological hallmarks: dopaminergic neuronal degeneration, α-synuclein accumulation and iron deposition. Over the last years, neuroimaging, particularly magnetic resonance imaging (MRI) has provided invaluable insights into the mechanisms underlying the disease. However, no imaging method has yet been able to translate α-synuclein protein accumulation and spreading. Amongst the animal models mimicking the disease, the α-synuclein rat, generated through the injection of human α-synuclein, has been characterized in terms of behavioural and histological aspects but not thoroughly explored in MRI. The aim of this study is, therefore, to identify the radiological signature from several MRI sequences, while controlling for histological and behavioural characteristics. Rats were assessed for motor and cognitive functions over a 4-month period. During this time, three MRI sessions, including both morphological and functional sequences, were conducted. Histological studies evaluated the three main hallmarks of PD. The progressive dopaminergic neurodegeneration and the spread of human α-synuclein corresponded to the level of sensorimotor, attentional and learning deficits observed in this PD model. MRI analyses showed progressive structural abnormalities in the midbrain, diencephalon and several cortical structures, as well as a pattern of hyperconnectivity in the basal ganglia and cortical networks. The regions affected in imaging demonstrated the highest load of human α-synuclein. This model's structural and functional MRI changes could serve as indirect indicators of α-synuclein accumulation and its association with impaired non-motor functions.