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1.  Assessment of genome and proteome profiles in cocaine abuse 
Progress in brain research  2006;158:173-195.
Until recently, knowledge of the impact of abuse drugs on gene and protein expression in the brain was limited to less than 100 targets. With the advent of high-throughput genomic and proteomic techniques investigators are now able to evaluate changes across the entire genome and across thousands of proteins in defined brain regions and generate expression profiles of vulnerable neuroanatomical substrates in rodent and non-human primate drug abuse models and in human post-mortem brain tissue from drug abuse victims. The availability of gene and protein expression profiles will continue to expand our understanding of the short- and long-term consequences of drug addiction and other addictive disorders and may provide new approaches or new targets for pharmacotherapeutic intervention. This chapter will review gene expression data from rodent, non-human primate and human post-mortem studies of cocaine abuse and will provide a preliminary proteomic profile of human cocaine abuse and explore how these studies have advanced our understanding of addiction.
PMCID: PMC4048548  PMID: 17027697
microarray; RNA amplification; gene expression; molecular fingerprint; qPCR; transcriptome; proteome; brain; post-mortem; monkey
2.  Saccades, salience and attention: the role of the lateral intraparietal area in visual behavior 
Progress in brain research  2006;155:157-175.
Neural activity in the lateral intraparietal area (LIP) has been associated with attention to a location in visual space, and with the intention to make saccadic eye movement. In this study we show that neurons in LIP respond to recently flashed task-irrelevant stimuli and saccade targets brought into the receptive field by a saccade, although they respond much to the same stimuli when they are stable in the environment. LIP neurons respond to the appearance of a flashed distractor even when a monkey is planning a memory-guided delayed saccade elsewhere. We then show that a monkey’s attention, as defined by an increase in contrast sensitivity, is pinned to the goal of a memory-guided saccade throughout the delay period, unless a distractor appears, in which case attention transiently moves to the site of the distractor and then returns to the goal of the saccade. LIP neurons respond to both the saccade goal and the distractor, and this activity correlates with the monkey’s locus of attention. In particular, the activity of LIP neurons predicts when attention migrates from the distractor back to the saccade goal. We suggest that the activity in LIP provides a salience map that is interpreted by the oculomotor system as a saccade goal when a saccade is appropriate, and simultaneously is used by the visual system to determine the locus of attention.
PMCID: PMC3615538  PMID: 17027387
lateral intraparietal area; saccade; attention; contrast sensitivity; monkey
3.  Segmental organization of spinal reflexes mediating autonomic dysreflexia after spinal cord injury 
Progress in brain research  2006;152:265-274.
Spinal cord injuries above mid-thoracic levels can lead to a potentially life-threatening hypertensive condition termed autonomic dysreflexia that is often triggered by distension of pelvic viscera (bladder or bowel). This syndrome is characterized by episodic hypertension due to sudden, massive discharge of sympathetic preganglionic neurons in the thoracolumbar spinal cord. This hypertension is usually accompanied by bradycardia, particularly if the injury is caudal to the 2nd to 4th thoracic spinal segments. The development of autonomic dysreflexia is correlated with aberrant sprouting of peptidergic afferent fibers into the spinal cord below the injury. In particular, sprouting of nerve growth factor-responsive afferent fibers has been shown to have a major influence on dysreflexia, perhaps by amplifying the activation of disinhibited sympathetic neurons. Using a model of noxious bowel distension after complete thoracic spinal transection at the 4th thoracic segment in rats, we selectively altered C-fiber sprouting, at specified spinal levels caudal to the injury, with microinjections of adenovirus encoding the growth-promoting nerve growth factor or the growth-inhibitory semaphorin 3A. This was followed by assessment of physiological responses to colorectal distension and subsequent histology. Additionally, anterograde tract tracers were injected into the lumbosacral region to compare the extent of labeled propriospinal rostral projections in uninjured cords to those incords after complete 4th thoracic transection. In summary, over-expression of chemorepulsive semaphorin 3A impeded C-fiber sprouting in lumbosacral segments and mitigated hypertensive autonomic dysreflexia, whereas the opposite results were obtained with nerve growth factor over-expression. Furthermore, compared to naïve rats there were significantly more labeled lumbosacral propriospinal projections rostrally after thoracic injury. Collectively, our findings suggest that distension of pelvic viscera increases the excitation of expanded afferent terminals in the disinhibited lumbosacral spinal cord. This, in turn, triggers excitation and sprouting of local propriospinal neurons to relay visceral sensory stimuli and amplify the activation of sympathetic preganglionic neurons in the thoracolumbar cord, to enhance transmission in the spinal viscero-sympathetic reflex pathway. These responses are manifested as autonomic dysreflexia.
PMCID: PMC3529572  PMID: 16198706
nerve growth factor; semaphorin3A; sprouting; sympathetic; neurotrophin; propriospinal; gene therapy
4.  Retinogeniculate connections: a balancing act between connection specificity and receptive field diversity 
Progress in brain research  2006;154:3-13.
Retinogeniculate connections are one of the most striking examples of connection specificity within the visual pathway. In almost every connection there is one dominant afferent per geniculate cell, and both afferent and geniculate cell have very similar receptive fields. The remarkable specificity and strength of retinogeniculate connections have inspired comparisons of the lateral geniculate nucleus (LGN) with a simple relay that connects the retina with visual cortex. However, because each retinal ganglion cell diverges to innervate multiple cells in LGN, most geniculate cells must receive additional inputs from other retinal afferents that are not the dominant one. These additional afferents make weaker connections and their receptive fields are not as perfectly matched with the geniculate target as the dominant afferent. We argue that these ‘match imperfections’ are important to create receptive field diversity among the cells that represent each point of visual space in LGN. We propose that the convergence of dominant and weak retinal afferents in LGN multiplexes the array of retinal ganglion cells by creating receptive fields that have a richer range of positions, sizes and response time-courses than those available at the ganglion cell layer of the retina.
PMCID: PMC2547345  PMID: 17010700
Thalamus; thalamocortical; visual cortex; V1; Y cell; X cell; response latency; simultaneous recording
5.  Source analysis of EEG oscillations using high-resolution EEG and MEG 
Progress in brain research  2006;159:29-42.
We investigated spatial properties of the source distributions that generate scalp electroencephalographic (EEG) oscillations. The inherent complexity of the spatiotemporal dynamics of EEG oscillations indicates that conceptual models that view source activity as consisting of only of a few “equivalent dipoles” are inadequate. We present an approach that uses volume conduction models to characterize the distinct spatial filtering of cortical source activity by average-reference EEG, high-resolution EEG, and magnetoencephalography (MEG). By comparing these three measures, we can make inferences about the sources of EEG oscillations without having to make prior assumptions about the sources. We apply this approach to spontaneous EEG oscillations observed with eyes closed at rest. Both EEG and MEG recordings show robust alpha rhythms over posterior regions of the cortex; however, the dominant frequency of these rhythms varies between EEG and MEG recordings. Frontal alpha and theta rhythms are generated almost exclusively by superficial radial dipole layers that generate robust EEG signals but very little MEG signals; these sources are presumably mainly in the gyral crowns of frontal cortex. MEG and high-resolution EEG estimates of alpha rhythms provide evidence of local tangential and radial sources in the posterior cortex, lying mainly on sulcal and gyral surfaces. Despite the detailed information about local radial and tangential sources potentially afforded by high-resolution EEG and MEG, it is also evident that the alpha and theta rhythms receive contributions from non-local source activity, for instance large dipole layers distributed over lobeal or (potentially) even larger spatial scales.
PMCID: PMC1995013  PMID: 17071222
high-resolution; electroencephalography (EEG); magnetoencephalography (MEG); source localization; alpha rhythms; theta rhythms

Results 1-5 (5)