Faculty Bibliography

The purpose of this study is to assess the image quality and diagnostic accuracy of non-contrast quadruple inversion-recovery balanced-SSFP MRA (QIR MRA) for detection of aortoiliac disease in a clinical population. QIR MRA was performed in 26 patients referred for routine clinical gadolinium-enhanced MRA (Gd-MRA) for known or suspected aortoiliac disease. Non-contrast images were independently evaluated for image quality and degree of stenosis by two radiologists, using consensus Gd-MRA as the reference standard. Hemodynamically significant stenosis (>/=50%) was found in 10% (22/226) of all evaluable segments on Gd-MRA. The sensitivity and specificity for stenosis evaluation by QIR MRA for the two readers were 86%/86% and 95%/93% respectively. Negative predictive value and positive predictive value were 98%/98% and 63%/53% respectively. For stenosis evaluation of the aortoiliac region QIR MRA showed good agreement with the reference standard with high negative predictive value and a tendency to overestimate mild disease presumably due to the flow-dependence of the technique. QIR MRA could be a reasonable alternative to Gd-MRA for ruling out stenosis when contrast is contraindicated due to impaired kidney function or in patients who undergo abdominal MRA for screening purposes. Further work is necessary to improve performance and justify routine clinical use.

Tight regulation of calcium entry through the L-type calcium channel CaV1.2 ensures optimal excitation-response coupling. In this issue of Neuron, Michailidis et al. (2014) demonstrate that CaV1.2 activity triggers negative feedback regulation through proteolytic cleavage of the channel within the core of the pore-forming subunit.

Hereditary sensory and autonomic neuropathy type III (HSAN III, Riley-Day syndrome, Familial Dysautomia) is characterised by elevated thermal thresholds and an indifference to pain. Using microelectrode recordings we recently showed that these patients possess no functional stretch-sensitive mechanoreceptors in their muscles (muscle spindles), a feature that may explain their lack of stretch reflexes and ataxic gait, yet patients have apparently normal low-threshold cutaneous mechanoreceptors. The density of C-fibres in the skin is markedly reduced in patients with HSAN III, but it is not known whether the C-tactile afferents, a distinct type of low-threshold C fibre present in hairy skin that is sensitive to gentle stroking and has been implicated in the coding of pleasant touch are specifically affected in HSAN III patients. We addressed the relationship between C-tactile afferent function and pleasant touch perception in 15 patients with HSAN III and 15 age-matched control subjects. A soft make-up brush was used to apply stroking stimuli to the forearm and lateral aspect of the leg at five velocities: 0.3, 1, 3, 10 and 30cm/s. As demonstrated previously, the control subjects rated the slowest and highest velocities as less pleasant than those applied at 1-10cm/s, which fits with the optimal velocities for exciting C-tactile afferents. Conversely, for the patients, ratings of pleasantness did not fit the profile for C-tactile afferents. Patients either rated the higher velocities as more pleasant than the slow velocities, with the slowest velocities being rated unpleasant, or rated all velocities equally pleasant. We interpret this to reflect absent or reduced C-tactile afferent density in the skin of patients with HSAN III, who are likely using tactile cues (i.e. myelinated afferents) to rate pleasantness of stroking or are attributing pleasantness to this type of stimulus irrespective of velocity.

In many systems, sleep plays a vital role in memory consolidation and synaptic homeostasis. These processes together help store information of biological significance and reset synaptic circuits to facilitate acquisition of information in the future. In this review, we describe recent evidence of sleep-dependent changes in olfactory system structure and function which contribute to odor memory and perception. During slow-wave sleep, the piriform cortex becomes hypo-responsive to odor stimulation and instead displays sharp-wave activity similar to that observed within the hippocampal formation. Furthermore, the functional connectivity between the piriform cortex and other cortical and limbic regions is enhanced during slow-wave sleep compared to waking. This combination of conditions may allow odor memory consolidation to occur during a state of reduced external interference and facilitate association of odor memories with stored hedonic and contextual cues. Evidence consistent with sleep-dependent odor replay within olfactory cortical circuits is presented. These data suggest that both the strength and precision of odor memories is sleep-dependent. The work further emphasizes the critical role of synaptic plasticity and memory in not only odor memory but also basic odor perception. The work also suggests a possible link between sleep disturbances that are frequently co-morbid with a wide range of pathologies including Alzheimer's disease, schizophrenia and depression and the known olfactory impairments associated with those disorders.

Hox genes have been shown to be essential in vertebrate neural circuit formation and their depletion has resulted in homeotic transformations with neuron loss and miswiring. Here we quantifiy four eye movements in the zebrafish mutant valentino and hox3 knockdowns, and find that contrary to the classical model, oculomotor circuits in hindbrain rhombomeres 5-6 develop and function independently of hox3 genes. All subgroups of oculomotor neurons are present, as well as their input and output connections. Ectopic connections are also established, targeting two specific subsets of horizontal neurons, and the resultant novel eye movements coexists with baseline behaviours. We conclude that the high expression of hox3 genes in rhombomeres 5-6 serves to prevent aberrant neuronal identity and behaviours, but does not appear to be necessary for a comprehensive assembly of functional oculomotor circuits.

BACKGROUND: We have extended our cerebellar cortical interneuron classification algorithm that uses statistics of spontaneous activity (Ruigrok et al., 2011) to include Purkinje cells. Purkinje cells were added because they do not always show a detectable complex spike, which is the accepted identification. The statistical measures used in the present study were obtained from morphologically identified interneurons and complex spike identified Purkinje cells, recorded from ketamine-xylazine anesthetized rats and rabbits, and from awake rabbits. NEW METHOD: The new algorithm has an added decision step that classifies Purkinje cells using a combination of the median absolute difference from the median interspike interval (MAD) and the mean of the relative differences of successive interspike intervals (CV2). These measures reflect the high firing rate and intermediate regularity of Purkinje cell simple spike activity. RESULTS: Of 86 juxtacellularly labeled interneurons and 110 complex spike-identified Purkinje cells, 61 interneurons and 95 Purkinje cells were correctly classified, 22 interneurons and 13 Purkinje cells were deemed unclassifiable, and 3 interneurons and 2 Purkinje cells were incorrectly classified. COMPARISON WITH EXISTING METHODS: The new algorithm improves on our previous algorithm because it includes Purkinje cells. This algorithm is the only one for the cerebellum that does not presume anatomical knowledge of whether the cells are in the molecular layer or the granular layer. CONCLUSIONS: These results strengthen the view that the new decision algorithm is useful for identifying neurons recorded at all cerebellar depths, particularly those neurons recorded in the rabbit vestibulocerebellum.

Maternal choline supplementation (MCS) induces lifelong cognitive benefits in the Ts65Dn mouse, a trisomic mouse model of Down syndrome and Alzheimer's disease. To gain insight into the mechanisms underlying these beneficial effects, we conducted a study to test the hypothesis that MCS alters choline metabolism in adult Ts65Dn offspring. Deuterium-labeled methyl-d9-choline was administered to adult Ts65Dn and disomic (2N) female littermates born to choline-unsupplemented or choline-supplemented Ts65Dn dams. Enrichment of d9-choline metabolites (derived from intact choline) and d3 + d6-choline metabolites [produced when choline-derived methyl groups are used by phosphatidylethanolamine N-methyltransferase (PEMT)] was measured in harvested tissues. Adult offspring (both Ts65Dn and 2N) of choline-supplemented (vs. choline-unsupplemented) dams exhibited 60% greater (P