Faculty Bibliography

Efficient coding provides a powerful principle for explaining early sensory coding. Most attempts to test this principle have been limited to linear, noiseless models, and when applied to natural images, have yielded oriented filters consistent with responses in primary visual cortex. Here we show that an efficient coding model that incorporates biologically realistic ingredients - input and output noise, nonlinear response functions, and a metabolic cost on the firing rate - predicts receptive fields and response nonlinearities similar to those observed in the retina. Specifically, we develop numerical methods for simultaneously learning the linear filters and response nonlinearities of a population of model neurons, so as to maximize information transmission subject to metabolic costs. When applied to an ensemble of natural images, the method yields filters that are center-surround and nonlinearities that are rectifying. The filters are organized into two populations, with On- and Off-centers, which independently tile the visual space. As observed in the primate retina, the Off-center neurons are more numerous and have filters with smaller spatial extent. In the absence of noise, our method reduces to a generalized version of independent components analysis, with an adapted nonlinear "contrast" function; in this case, the optimal filters are localized and oriented.

Several lines of research have now suggested the controversial hypothesis that the central noradrenergic system acts to exacerbate depression as opposed to having an antidepressant function. If correct, lesions of this system should increase resistance to depression, which has been partially but weakly supported by previous studies. The present study reexamined this question using two more recent methods to lesion noradrenergic neurons in mice: intraventricular (ivt) administration of either the noradrenergic neurotoxin, DSP4, or of a dopamine-beta-hydroxylase-saporin immunotoxin (DBH-SAP ITX) prepared for mice. Both agents given 2weeks prior were found to significantly increase resistance to depressive behavior in several tests including acute and repeated forced swims, tail suspension and endotoxin-induced anhedonia. Both agents also increased locomotor activity in the open field. Cell counts of brainstem monoaminergic neurons, however, showed that both methods produced only partial lesions of the locus coeruleus and also affected the dorsal raphe or ventral tegmental area. Both the cell damage and the antidepressant and hyperactive effects of ivt DSP4 were prevented by a prior i.p. injection of the NE uptake blocker, reboxetine. The results are seen to be consistent with recent pharmacological experiments showing that noradrenergic and serotonergic systems function to inhibit active behavior. Comparison with previous studies utilizing more complete and selective LC lesions suggest that mouse strain, lesion size or involvement of multiple neuronal systems are critical variables in the behavioral and affective effects of monoaminergic lesions and that antidepressant effects and hyperactivity may be more likely to occur if lesions are partial and/or involve multiple monoaminergic systems

Background- The specialized cardiac conduction system (CCS) expresses a unique complement of ion channels that confer a specific electrophysiological profile. ATP-sensitive potassium (K(ATP)) channels in these myocytes have not been systemically investigated. Methods and Results- We recorded K(ATP) channels in isolated CCS myocytes using Cntn2-EGFP reporter mice. The CCS K(ATP) channels were less sensitive to inhibitory cytosolic ATP compared with ventricular channels and more strongly activated by MgADP. They also had a smaller slope conductance. The 2 types of channels had similar intraburst open and closed times, but the CCS K(ATP) channel had a prolonged interburst closed time. CCS K(ATP) channels were strongly activated by diazoxide and less by levcromakalim, whereas the ventricular K(ATP) channel had a reverse pharmacological profile. CCS myocytes express elevated levels of Kir6.1 but reduced Kir6.2 and SUR2A mRNA compared with ventricular myocytes (SUR1 expression was negligible). SUR2B mRNA expression was higher in CCS myocytes relative to SUR2A. Canine Purkinje fibers expressed higher levels of Kir6.1 and SUR2B protein relative to the ventricle. Numeric simulation predicts a high sensitivity of the Purkinje action potential to changes in ATP:ADP ratio. Cardiac conduction time was prolonged by low-flow ischemia in isolated, perfused mouse hearts, which was prevented by glibenclamide. Conclusions- These data imply a differential electrophysiological response (and possible contribution to arrhythmias) of the ventricular CCS to K(ATP) channel opening during periods of ischemia

PURPOSE: To investigate arterial flow characteristics in the setting of vascular disease, and examine their effect on the performance of fast spin-echo (FSE)-based noncontrast MR angiography (NC-MRA). MATERIALS AND METHODS: Seventeen patients were recruited from among those scheduled for routine contrast-enhanced MR angiography (CE-MRA) of the lower extremities at 1.5 Tesla. The research portion of the exam was performed before the clinically-indicated protocol and included phase-contrast imaging at multiple levels in the legs and FSE-based NC-MRA in the calf and thigh, using a three-dimensional ECG-gated technique that exploits differences in arterial flow velocity between diastole and systole. RESULTS: Vascular occlusions were associated with reduced systolic velocity, a delayed systolic peak, and, in two middle-aged patients, an increase in diastolic velocity. Elevated systolic and diastolic velocities were observed in a subject with a nonhealing ulcer. NC-MRA allowed visualization of arteries with systolic velocities as low as 3 cm/s, and exhibited comparable depiction to CE-MRA for diastolic velocities as high as 6 cm/s. At the highest diastolic velocities observed (15 cm/s) arterial depiction was severely degraded. CONCLUSION: FSE-based NC-MRA as presently implemented performs successfully over a wide range of flow patterns, but does not accommodate extremely low systolic velocities or very high diastolic velocities. J. Magn. Reson. Imaging 2011;. (c) 2011 Wiley Periodicals, Inc

Experience shapes both central olfactory system function and odor perception. In piriform cortex, odor experience appears critical for synthetic processing of odor mixtures which contributes to perceptual learning and perceptual acuity, as well as contributing to memory for events and/or rewards associated with odors. Here, we examined the effect of odor fear conditioning on piriform cortical single-unit responses to the learned aversive odor, as well as its effects on similar (overlapping mixtures) in freely moving rats. We found that odor-evoked fear responses were training paradigm-dependent. Simple association of a CS+ odor with foot-shock (US) led to generalized fear (cue-evoked freezing) to similar odors. However, after differential conditioning, which included trials where a CS- odor (a mixture overlapping with the CS+) was not paired with shock, freezing responses were CS+ odor-specific and less generalized. Pseudo-conditioning led to no odor-evoked freezing. These differential levels of stimulus control over freezing were associated with different training-induced changes in single-unit odor responses in anterior piriform cortex (aPCX). Both simple and differential conditioning induced a significant decrease in aPCX single-unit spontaneous activity compared to pre-training levels while pseudo-conditioning did not. Simple conditioning enhanced mean receptive field size (breadth of tuning) of the aPCX units, while differential conditioning reduced mean receptive field size. These results suggest that generalized fear is associated with an impairment of olfactory cortical discrimination. Furthermore, changes in sensory processing are dependent on the nature of training, and can predict the stimulus controlled behavioral outcome of the training

The question of what modulates the firing of the cerebellar nuclei (CN) is one to which we presently have a surprisingly incomplete answer. Because most synaptic input to the CN originates from Purkinje cells (PCs), and simple spikes (SSs) are far more numerous than complex spikes (CSs), SSs are generally thought to be the dominant influence on the CN. However, evidence, reviewed here, suggests that this appears not to be the case in some physiologically important situations. As an alternative, we propose that CS activity may have at least as significant an effect on CN firing as do SSs. In particular, we suggest that CS activity has a role in controlling the bursts CN neurons show during various movements, during sleep states, and under ketamine-xylazine anesthesia. The ability to perform this role rests on the fact that CSs can be highly synchronized among PCs that project to the same CN neuron. Specifically, we suggest that synchronized CSs help determine the temporal course of the CN bursts, most often their offset, and that SSs and activity from cerebellar afferents may modulate the specific firing pattern within each burst. This joint control of CN activity may help explain anomalies present in the standard model for synaptic control of CN activity in which determination of CN firing patterns is attributed primarily to SSs