1,036 research outputs found
Nicotine exposure during adolescence leads to short- and long-term changes in spike timing-dependent plasticity in rat prefrontal cortex
Adolescence is a critical period of brain development during which maturation of areas involved in cognitive functioning, such as the medial prefrontal cortex (mPFC), is still ongoing. Tobacco smoking during this age can compromise the normal course of prefrontal development and lead to cognitive impairments in later life. Recently, were ported that nicotine exposure during adolescence results in a short-term increase and lasting reduction in synaptic mGluR2 levels in the rat mPFC, causing attention deficits during adulthood. It is unknown how changed synaptic mGluR2 levels after adolescent nicotine exposure affect the ability of mPFC synapses to undergo long-term synaptic plasticity. Here, we addressed this question. To model nicotine exposure, adolescent (P34-P43) or adult (P60-P69) rats were treated with nicotine injections three times per day for 10 d. We found that, both during acute activation of nicotinic receptors in the adolescent mPFC as well as immediately following nicotine treatment during adolescence, long-term plasticity in response to timed presynaptic and postsynaptic activity (tLTP) was strongly reduced. In contrast, in the mPFC of adult rats 5 weeks after they received nicotine treatment during adolescence, but not during adulthood, tLTP was increased. Short-andlong-term adaptation of mPFC synaptic plasticity after adolescent nicotine exposure could be explained by changed mGluR2 signaling. Blocking mGluR2s augmented tLTP, where as activating mGluR2s reduced tLTP. Our findings suggest neuronal mechanisms by which exposure to nicotine during adolescence alters the rules for spike timing-dependent plasticity in prefrontal networks that may explain the observed deficits in cognitive performance in later life. © 2012 the authors
Nicotine exposure during adolescence alters the rules for prefrontal cortical synaptic plasticity during adulthood
The majority of adolescents report to have smoked a cigarette at least once. Adolescence is a critical period of brain development during which maturation of areas involved in cognitive functioning, such as the medial prefrontal cortex (mPFC), is still ongoing. Tobacco smoking during this age may compromise the normal course of prefrontal development and lead to cognitive impairments in later life. In addition, adolescent smokers suffer from attention deficits, which progress with the years of smoking. Recent studies in rodents reveal the molecular changes induced by adolescent nicotine exposure that alter the functioning of synapses in the PFC and underlie the lasting effects on cognitive function. In particular, the expression and function of metabotropic glutamate receptors (mGluRs) are changed and this has an impact on short- and long-term plasticity of glutamatergic synapses in the PFC and ultimately on the attention performance. Here, we review and discuss these recent findings
STDP and Mental Retardation: Dysregulation of Dendritic Excitability in Fragile X Syndrome
Development of cognitive function requires the formation and refinement of synaptic networks of neurons in the brain. Morphological abnormalities of synaptic spines occur throughout the brain in a wide variety of syndromic and non-syndromic disorders of mental retardation (MR). In both neurons from human post-mortem tissue and mouse models of retardation, the changes observed in synaptic spine and dendritic morphology can be subtle, in the range of 10–20% alterations for spine protrusion length and density. Functionally, synapses in hippocampus and cortex show deficits in long-term potentiation (LTP) and long-term depression (LTD) in an array of neurodevelopmental disorders including Down's, Angelman, Fragile X and Rett syndrome. Recent studies have shown that in principle the machinery for synaptic plasticity is in place in these synapses, but that significant alterations in spike-timing-dependent plasticity (STDP) induction rules exist in cortical synaptic pathways of Fragile X MR syndrome. In this model, the threshold for inducing timing-dependent long-term potentiation (tLTP) is increased in these synapses. Increased postsynaptic activity can overcome this threshold and induce normal levels of tLTP. In this review, we bring together recent studies investigating STDP in neurodevelopmental learning disorders using Fragile X syndrome as a model and we argue that alterations in dendritic excitability underlie deficits seen in STDP. Known and candidate dendritic mechanisms that may underlie the plasticity deficits are discussed. Studying STDP in monogenic MR syndromes with clear deficits in information processing at the cognitive level also provides the field with an opportunity to make direct links between cognition and processing rules at the synapse during development
Presynaptic Ionotropic Receptors Controlling and Modulating the Rules for Spike Timing-Dependent Plasticity
Throughout life, activity-dependent changes in neuronal connection strength enable the brain to refine neural circuits and learn based on experience. In line with predictions made by Hebb, synapse strength can be modified depending on the millisecond timing of action potential firing (STDP). The sign of synaptic plasticity depends on the spike order of presynaptic and postsynaptic neurons. Ionotropic neurotransmitter receptors, such as NMDA receptors and nicotinic acetylcholine receptors, are intimately involved in setting the rules for synaptic strengthening and weakening. In addition, timing rules for STDP within synapses are not fixed. They can be altered by activation of ionotropic receptors located at, or close to, synapses. Here, we will highlight studies that uncovered how network actions control and modulate timing rules for STDP by activating presynaptic ionotropic receptors. Furthermore, we will discuss how interaction between different types of ionotropic receptors may create “timing” windows during which particular timing rules lead to synaptic changes
The learning portfolio as a tool for stimulating reflection by student teachers
The topic of this study is the portfolio that is being used in a teacher education institute as an instrument for stimulating reflection on their development as teachers by student teachers. This reflection can be seen in the themes student teachers have written in their portfolios. The nature of reflection has been described by means of content analysis. The student teachers in this study mainly used their portfolios for examing what they had done and learned and much less for learning from these experiences. The results show that teacher education institutes must be very clear about what they aim at with reflection. Subsequently portfolio supervision and the use of the portfolio should be much better geared to this. Whether the portfolio is a suitable instrument for using in educating teachers should also be discussed.UBL - phd migration 201
Lack of nAChR Activity Depresses Cochlear Maturation and Up-Regulates GABA System Components: Temporal Profiling of Gene Expression in α9 Null Mice
It has previously been shown that deletion of chrna9, the gene encoding the alpha9 nicotinic acetylcholine receptor (nAChR) subunit, results in abnormal synaptic terminal structure. Additionally, all nAChR-mediated cochlear activity is lost, as characterized by a failure of the descending efferent system to suppress cochlear responses to sound. In an effort to characterize the molecular mechanisms underlying the structural and functional consequences following loss of alpha9 subunit expression, we performed whole-transcriptome gene expression analyses on cochleae of wild type and alpha9 knockout (alpha9(-/-)) mice during postnatal days spanning critical periods of synapse formation and maturation.Data revealed that loss of alpha9 receptor subunit expression leads to an up-regulation of genes involved in synaptic transmission and ion channel activity. Unexpectedly, loss of alpha9 receptor subunit expression also resulted in an increased expression of genes encoding GABA receptor subunits and the GABA synthetic enzyme, glutamic acid decarboxylase. These data suggest the existence of a previously unrecognized association between the nicotinic cholinergic and GABAergic systems in the cochlea. Computational analyses have highlighted differential expression of several gene sets upon loss of nicotinic cholinergic activity in the cochlea. Time-series analysis of whole transcriptome patterns, represented as self-organizing maps, revealed a disparate pattern of gene expression between alpha9(-/-) and wild type cochleae at the onset of hearing (P13), with knockout samples resembling immature postnatal ages.We have taken a systems biology approach to provide insight into molecular programs influenced by the loss of nicotinic receptor-based cholinergic activity in the cochlea and to identify candidate genes that may be involved in nicotinic cholinergic synapse formation, stabilization or function within the inner ear. Additionally, our data indicate a change in the GABAergic system upon loss of alpha9 nicotinic receptor subunit within the cochlea
Long-Range Amplitude Coupling Is Optimized for Brain Networks That Function at Criticality
Brain function depends on segregation and integration of information processing in brain networks often separated by long-range anatomic connections. Neuronal oscillations orchestrate such distributed processing through transient amplitude and phase coupling, yet surprisingly, little is known about local network properties facilitating these functional connections. Here, we test whether criticality, a dynamical state characterized by scale-free oscillations, optimizes the capacity of neuronal networks to couple through amplitude or phase, and transfer information. We coupled in silico networks which exhibit oscillations in the α band (8–16 Hz), and varied excitatory and inhibitory connectivity. We found that phase coupling of oscillations emerges at criticality, and that amplitude coupling, as well as information transfer, are maximal when networks are critical. Importantly, regulating criticality through modulation of synaptic gain showed that critical dynamics, as opposed to a static ratio of excitatory and inhibitory connections, optimize network coupling and information transfer. Our data support the idea that criticality is important for local and global information processing and may help explain why brain disorders characterized by local alterations in criticality also exhibit impaired long-range synchrony, even before degeneration of axonal connections. SIGNIFICANCE STATEMENT To perform adaptively in a changing environment, our brains dynamically coordinate activity across distant areas. Empirical evidence suggests that long-range amplitude and phase coupling of oscillations are systems-level mechanisms enabling transient formation of spatially distributed functional networks on the backbone of a relatively static structural connectome. However, surprisingly little is known about the local network properties that optimize coupling and information transfer. Here, we show that criticality, a dynamical state characterized by scale-free oscillations and a hallmark of neuronal network activity, optimizes the capacity of neuronal networks to couple through amplitude or phase and transfer information
EEG-Biofeedback as a Tool to Modulate Arousal: Trends and Perspectives for Treatment of ADHD and Insomnia
GABAergic Synapse Properties May Explain Genetic Variation in Hippocampal Network Oscillations in Mice
Cognitive ability and the properties of brain oscillation are highly heritable in humans. Genetic variation underlying oscillatory activity might give rise to differences in cognition and behavior. How genetic diversity translates into altered properties of oscillations and synchronization of neuronal activity is unknown. To address this issue, we investigated cellular and synaptic mechanisms of hippocampal fast network oscillations in eight genetically distinct inbred mouse strains. The frequency of carbachol-induced oscillations differed substantially between mouse strains. Since GABAergic inhibition sets oscillation frequency, we studied the properties of inhibitory synaptic inputs (IPSCs) received by CA3 and CA1 pyramidal cells of three mouse strains that showed the highest, lowest and intermediate frequencies of oscillations. In CA3 pyramidal cells, the frequency of rhythmic IPSC input showed the same strain differences as the frequency of field oscillations. Furthermore, IPSC decay times in both CA1 and CA3 pyramidal cells were faster in mouse strains with higher oscillation frequencies than in mouse strains with lower oscillation frequency, suggesting that differences in GABAA-receptor subunit composition exist between these strains. Indeed, gene expression of GABAA-receptor β2 (Gabrb2) and β3 (Gabrb2) subunits was higher in mouse strains with faster decay kinetics compared with mouse strains with slower decay kinetics. Hippocampal pyramidal neurons in mouse strains with higher oscillation frequencies and faster decay kinetics fired action potential at higher frequencies. These data indicate that differences in genetic background may result in different GABAA-receptor subunit expression, which affects the rhythm of pyramidal neuron firing and fast network activity through GABA synapse kinetics
An Algorithm for Finding Candidate Synaptic Sites in Computer Generated Networks of Neurons with Realistic Morphologies
Neurons make synaptic connections at locations where axons and dendrites are sufficiently close in space. Typically the required proximity is based on the dimensions of dendritic spines and axonal boutons. Based on this principle one can search those locations in networks formed by reconstructed neurons or computer generated neurons. Candidate synapses are then located where axons and dendrites are within a given criterion distance from each other. Both experimentally reconstructed and model generated neurons are usually represented morphologically by piecewise-linear structures (line pieces or cylinders). Proximity tests are then performed on all pairs of line pieces from both axonal and dendritic branches. Applying just a test on the distance between line pieces may result in local clusters of synaptic sites when more than one pair of nearby line pieces from axonal and dendritic branches is sufficient close, and may introduce a dependency on the length scale of the individual line pieces. The present paper describes a new algorithm for defining locations of candidate synapses which is based on the crossing requirement of a line piece pair, while the length of the orthogonal distance between the line pieces is subjected to the distance criterion for testing 3D proximity
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