Neuroscience
-
Stressful life events, especially those that induce fear, can produce a state of anxiety that is useful for avoiding similar fearful and potentially dangerous situations in the future. However, they can also lead to exaggerated states, which over time can produce mental illness. These changing states of readiness versus illness are thought to be regulated, at least in part, by alterations in dendritic and synaptic structure within brain regions known to be involved in anxiety. ⋯ We begin by highlighting the acute and chronic effects of stress on synaptic morphology in each area and describe some of the putative mechanisms that have been implicated in these effects. We then discuss the functional consequences of stress-induced structural plasticity focusing on synaptic plasticity as well as cognitive and emotional behaviors. Finally, we consider how these structural changes may contribute to adaptive behaviors as well as maladaptive responses associated with anxiety.
-
Schizophrenia is a neurodevelopmental disorder whose clinical features include impairments in perception, cognition and motivation. These impairments reflect alterations in neuronal circuitry within and across multiple brain regions that are due, at least in part, to deficits in dendritic spines, the site of most excitatory synaptic connections. ⋯ These spine deficits appear to arise during development, and thus are likely the result of disturbances in the molecular mechanisms that underlie spine formation, pruning, and/or maintenance. Each of these mechanisms may provide insight into novel therapeutic targets for preventing or repairing the alterations in neural circuitry that mediate the debilitating symptoms of schizophrenia.
-
In the striatum, the dendritic tree of the two main populations of projection neurons, called "medium spiny neurons (MSNs)", are covered with spines that receive glutamatergic inputs from the cerebral cortex and thalamus. In Parkinson's disease (PD), striatal MSNs undergo an important loss of dendritic spines, whereas aberrant overgrowth of striatal spines occurs following chronic cocaine exposure. This review examines the possibility that opposite dopamine dysregulation is one of the key factors that underlies these structural changes. ⋯ Recent studies have suggested that opposite calcium-mediated regulation of the transcription factor myocyte enhancer factor 2 (MEF2) function induces these structural defects. In conclusion, there is strong evidence that dopamine is a major, but not the sole, regulator of striatal spine pathology in PD and addiction to psychostimulants. Further studies of the role of glutamate and other genes associated with spine plasticity in mediating these effects are warranted.
-
Dendritic spines are the principal recipients of excitatory synaptic inputs and the basic units of neural computation in the mammalian brain. Alterations in the density, size, shape, and turnover of mature spines, or defects in how spines are generated and establish synapses during brain development, could all result in neuronal dysfunction and lead to cognitive and/or behavioral impairments. ⋯ Here, we argue that the most consistent abnormality of spines in FXS may be a subtle defect in activity-dependent spine plasticity and maturation. We also propose some future directions for research into spine plasticity in FXS at the cellular and ultrastructural levels that could help solve a two-decade-long riddle about the integrity of synapses in this prototypical neurodevelopmental disorder.
-
Abnormalities in dendritic spines have commonly been observed in brain specimens from epilepsy patients and animal models of epilepsy. However, the functional implications and clinical consequences of this dendritic pathology for epilepsy are uncertain. ⋯ In other situations, seizures themselves may cause damage to dendrites and dendritic spines and this seizure-induced brain injury may then contribute to progressive epileptogenesis, memory problems and other neurological deficits in epilepsy patients. The mechanistic basis of dendritic spine abnormalities in epilepsy has begun to be elucidated and suggests novel therapeutic strategies for treating epilepsy and its complications.