The Neuroscientist

A prevailing view in neuroscience is that the mature CNS has relatively little capacity to respond adaptively to injury. Recent data indicating a high degree of structural plasticity in the adult brain provides an impetus to reexamine how central neurons react to trauma. An analysis of both in vivo and in vitro experimental studies demonstrates that certain brain neurons may have an intrinsic ability to respond to structural injury by an attempt at regenerative sprouting. Indeed, aberrant sprouting following neuronal injury may be the cause of epilepsy following brain trauma and may underlie the neuronal changes stimulated by plaque formation in Alzheimer’s disease. An understanding of the stereotypical reaction to injury of different CNS neurons, as well as the role of nonneuronal cells, may provide new avenues for therapeutic intervention for a range of neurodegenerative diseases and “acquired” forms of CNS injury.

In mammals, alertness and foraging are linked to the light-dark cycle and body energy levels. This link is crucially dependent on the novel peptide transmitters orexins/hypocretins. The firing of orexin neurons encodes the overall internal (body energy levels) and external (time of day) environment. In turn, orexins modulate arousal and appetite by innervating and electrically exciting wakeand appetitepromoting neurons. Electrical signaling in orexin circuits thereby couples arousal to the environment and synchronizes foraging with states of high alertness.

Identifying and defining the characteristic features of the inhibitory neurons in the nervous system has become essential for achieving a cellular understanding of complex brain activities. For this, the olfactory bulb is ideally suited because it is readily accessible, it is a laminated structure where local interneurons can be easily distinguished from projecting neurons, and, more important, GABAergic interneurons are continuously replaced. How the newly generated neurons integrate into a preexisting neural network and how basic network functions are maintained when a large percentage of neurons are subjected to continuous renewal are important questions that have recently received new insights. Here, it is seen that the production of bulbar interneurons is specifically adapted to experience-dependent regulation of adult neural networks. In particular, the authors report the degree of sensitivity of the bulbar neurogenesis to the activity level of sensory inputs and, in turn, how the adult neurogenesis adjusts the neural network functioning to optimize information processing. By maintaining a constitutive neurogenesis sensitive to environmental cues, this neuronal recruitment leads to improving sensory abilities. This review brings together recently described properties and emerging principles of interneuron functions that may convey, into bulbar neuronal networks, a degree of circuit adaptation unmatched by synaptic plasticity alone.

Compelling new findings have revealed that receptor tyrosine kinases of the Eph family, along with their ephrin ligands, play an essential role in regulating the properties of developing mature excitatory synapses in the central nervous system. The cell surface localization of both the Eph receptors and the ephrins enables these proteins to signal bidirectionally at sites of cell-to-cell contact, such as synapses. Eph receptors and ephrins have indeed been implicated in multiple aspects of synaptic function, including clustering and modulating N-methyl-D-aspartate receptors, modifying the geometry of postsynaptic terminals, and influencing long-term synaptic plasticity and memory. In this review, we discuss how Eph receptors and ephrins are integrated into the molecular machinery that supports synaptic function.

The hypothalamic suprachiasmatic nucleus (SCN) has a pivotal role in the mammalian circadian clock. SCN neurons generate circadian rhythms in action potential firing frequencies and neurotransmitter release, and the core oscillation is thought to be driven by “clock gene” transcription-translation feedback loops. Cytosolic Ca²⁺ mobilization followed by stimulation of various receptors has been shown to reset the gene transcription cycles in SCN neurons, whereas contribution of steady-state cytosolic Ca²⁺ levels to the rhythm generation is unclear. Recently, circadian rhythms in cytosolic Ca²⁺ levels have been demonstrated in cultured SCN neurons. The circadian Ca²⁺ rhythms are driven by the release of Ca²⁺ from ryanodine-sensitive internal stores and resistant to the blockade of action potentials. These results raise the possibility that gene translation/transcription loops may interact with autonomous Ca²⁺ oscillations in the production of circadian rhythms in SCN neurons.

One of the major targets for ethanol (alcohol) in the brain is the N-methyl-D-aspartate (NMDA) receptor, a glutamate-gated ion channel. Intriguingly, the effects of ethanol on the NMDA receptor are not homogeneous throughout the brain. This review focuses on recent studies revealing molecular mechanisms that mediate the actions of ethanol on the NMDA receptor in different brain regions via changes in NMDA receptor phosphorylation and compartmentalization. Specifically, the role of the scaffolding protein RACK1 and the regulatory protein DARPP-32 in mediating the distinct effects of ethanol is presented.

One of the fundamental features of the visual system is the segregation of neural circuits that process increments and decrements of luminance into ON and OFF pathways. In mature retina, the dendrites of retinal ganglion cells (RGCs) in the inner plexiform layer (IPL) of retina are separated into ON or OFF sublaminaspecific stratification. At an early developmental stage, however, the dendrites of most RGCs are ramified throughout the IPL. The maturation of RGC ON/OFF dendritic stratification requires neural activities mediated by afferent inputs from bipolar and amacrine cells. The synchronized spontaneous burst activities in early postnatal developing retina regulate RGC dendritic filopodial movements and the maintenance or elimination of dendritic processes. After eye opening, visual experience further remodels and consolidates the retinal neural circuit into mature forms. Several neurotransmitter systems, including glutamatergic, acetylcholinergic, GAB Aergic, and glycinergic systems, might act together to modulate the RGC dendritic refinement. In addition, both the bipolar cells and cholinergic amacrine cells may provide laminar cues for the maturation of RGC dendritic stratification.

Walking can be a very automated process, and it is likely that central pattern generators (CPGs) play a role in the coordination of the limbs. Recent evidence suggests that both the arms and legs are regulated by CPGs and that sensory feedback also regulates the CPG activity and assists in mediating interlimb coordination. Although the strength of coupling between the legs is stronger than that between the arms, arm and leg movements are similarly regulated by CPG activity and sensory feedback (e.g., reflex control) during locomotion.

A neuroanatomical description of dyslexia has been elusive, due in part to the complex cognitive nature of dyslexia. People with dyslexia have varying degrees of impairment in reading skills that engage oral and written language (reading) neural networks. Although findings for the inferior parietal lobule, inferior frontal gyrus, and cerebellum have been relatively consistent across studies, these studies also demonstrate that anatomical patterns of results vary according to the reading skills that characterize dyslexia. The number and likelihood of atypical anatomical findings in oral and/or written language systems appears to be related to the pattern of impairments in measures of phonology, orthography, and fluency. A comprehensive neurobiological understanding of dyslexia will depend on studies of dyslexic individuals with homogeneous perceptual, cognitive, and genetic backgrounds.

In this review, the authors summarize the literature on brain morphological changes that occur throughout the human life span from childhood into old age. They examine changes observed postmortem and in vivo where various brain MRI analytic methods have been applied. They evaluate brain changes observed with volumetric image analytic methods and voxel-based morphometric methods that may be used to better localize where changes occur. The primary focus of the review is on recent studies using state-of-the-art cortical pattern-matching techniques to assess age-related changes in cortical asymmetries, gray matter distribution, and brain growth across various age spans. The authors attempt to integrate findings from the in vivo studies with results from postmortem studies and analyze the complicated question of when brain maturation stops and brain aging begins. Analyzing the regional patterns of change initiated at various ages may help elucidate relationships between changing brain morphology and changing cognitive functions that occur throughout life. Long-range longitudinal studies, correlations between imaging and postmortem data, and more advanced image acquisition and analysis technologies will be needed to fully interpret brain morphological changes observed in vivo in relation to development and aging.