Journal of Neurophysiology

Lafourcade, Carlos A.

doi: 10.1152/jn.00441.2009pmid: 19553483

Abstract Endogenous cannabinoids (eCBs) mobilized from postsynaptic cells activate presynaptic cannabinoid receptors and thereby inhibit synaptic transmitter release. The inhibition can be either brief (seconds) or long-lasting (minutes to hours). Recent studies provide insight into the presynaptic mechanisms responsible for long-lasting, eCB-mediated long-term depression. Among these, the proteins PKA and RIM1α appear to be crucial, although other possibilities are emerging. Copyright © 2009 The American Physiological Society

Osborne, Leslie C.; Lisberger, Stephen G.

doi: 10.1152/jn.00611.2009pmid: 19657083

Abstract To probe how the brain integrates visual motion signals to guide behavior, we analyzed the smooth pursuit eye movements evoked by target motion with a stochastic component. When each dot of a texture executed an independent random walk such that speed or direction varied across the spatial extent of the target, pursuit variance increased as a function of the variance of visual pattern motion. Noise in either target direction or speed increased the variance of both eye speed and direction, implying a common neural noise source for estimating target speed and direction. Spatial averaging was inefficient for targets with >20 dots. Together these data suggest that pursuit performance is limited by the properties of spatial averaging across a noisy population of sensory neurons rather than across the physical stimulus. When targets executed a spatially uniform random walk in time around a central direction of motion, an optimized linear filter that describes the transformation of target motion into eye motion accounted for ∼50% of the variance in pursuit. Filters had widths of ∼25 ms, much longer than the impulse response of the eye, and filter shape depended on both the range and correlation time of motion signals, suggesting that filters were products of sensory processing. By quantifying the effects of different levels of stimulus noise on pursuit, we have provided rigorous constraints for understanding sensory population decoding. We have shown how temporal and spatial integration of sensory signals converts noisy population responses into precise motor responses. Copyright © 2009 The American Physiological Society

Mottram, Carol J.; Suresh, Nina L.; Heckman, C. J.; Gorassini, Monica A.; Rymer, William Z.

doi: 10.1152/jn.00151.2009pmid: 19587321

Abstract Stroke survivors often exhibit abnormal motoneuron excitability, manifested clinically as spasticity with exaggerated stretch reflexes in resting muscles. We examined whether this abnormal excitability is a result of increased activation of intrinsic voltage-dependent persistent inward currents (PICs) or whether it is a result of enhanced synaptic inputs to the motoneuron. This distinction was made by recording firing rate profiles of pairs of motor units during isometric contractions of elbow flexor muscles. To estimate PIC amplitude, the discharge of the lower-threshold (reporter) motor unit of the pair was used to estimate the synaptic input to the higher-threshold (test) motor unit. The estimated synaptic input required to recruit the test unit was compared with the synaptic input when the test unit was derecruited (Δ F ) and this served as an estimate of the intrinsic (PIC) contribution to motoneuron firing. We found that PIC estimates were not larger in spastic-paretic motoneurons (Δ F = 4.0 ± 1.6 pps) compared with contralateral (4.6 ± 1.4 pps) and age-matched healthy control motoneurons (3.8 ± 1.7, all P > 0.1). Instead, following the voluntary contractions, the majority of lower-threshold motor units in spastic-paretic muscles (83%) exhibited spontaneous discharge, compared with 14% of contralateral and 0% of control motor units. Furthermore, there was strong co-modulation of simultaneously active units in spastic muscle. The presence of ongoing, correlated unit activity at “rest,” coupled with firing behavior at recruitment unique to lower-threshold motor units in spastic muscles, suggested that firing changes are likely a result of a low-level depolarizing synaptic drive to the resting motoneuron pool. Copyright © 2009 The American Physiological Society

Medina, Javier F.; Lisberger, Stephen G.

doi: 10.1152/jn.00075.2009pmid: 19625543

Abstract We recorded the simple-spike (SS) firing of Purkinje cells (PCs) in the floccular complex both during normal pursuit caused by step-ramp target motions and after learning induced by a consistently timed change in the direction of target motion. The encoding of eye movement by the SS firing rate of individual PCs was described by a linear regression model, in which the firing rate is a sum of weighted components related to eye acceleration, velocity, and position. Although the model fit the data well for individual conditions, the regression coefficients for the learned component of firing often differed substantially from those for normal pursuit of step-ramp target motion. We suggest that the different encoding of learned versus normal pursuit responses in individual PCs reflects different amounts of learning in their inputs. The decoded output from the floccular complex, estimated by averaging responses across the population of PCs, also was fitted by the regression model. Regression coefficients were equal for the two conditions for on-direction pursuit, but differed for off-direction target motion. We conclude that the average output from the population of floccular PCs provides some, but not all, of the neural signals that drive the learned component of pursuit and that plasticity outside of the flocculus makes an important contribution. Copyright © 2009 The American Physiological Society

Weible, Aldis P.; Rowland, David C.; Pang, Raina; Kentros, Clifford

doi: 10.1152/jn.00214.2009pmid: 19587319

Abstract The anterior cingulate cortex (ACC) is a component of the limbic system implicated in a wide variety of functions spanning motor and sensory information processing, memory, attention, novelty detection, and comparisons of expectation versus outcome. It remains unclear how much of this functional diversity stems from differences in methodology or interpretation versus truly reflecting the range of processes in which the ACC is involved. In the present study, ACC neuronal activity was examined in freely behaving mice (C57BL6/J) under conditions allowing investigation of many of the cited functions in conditions free from externally applied rules: tests of novel object and novel location recognition memory. Behavioral activity and neuronal activity were recorded first in the open field, during the initial exposure and subsequent familiarization to two identical objects, and finally during the recognition memory tests. No discernible stable firing correlates of ACC neurons were found in the open field, but the addition of objects led to lasting changes in the firing patterns of many ACC neurons around one or both of the object locations. During the novel location test, some neurons followed the familiar object to its new location, others fired exclusively where the object had been, and yet others fired to both current and former object locations. Many of these same features were observed during tests of object recognition memory. However, the magnitude of the neuronal preference for the novel or the familiar object was markedly greater than that observed during either the tests of location recognition or novel object preferences in animals that did not exhibit the expected behavior. The present study reveals, for the first time, single-neuron correlates of object and location recognition behaviors in the rodent ACC and suggests that neurons of the ACC provide a distributed representation of all of the salient features of a task. Footnotes Copyright © 2009 The American Physiological Society

Shushruth, S.; Ichida, Jennifer M.; Levitt, Jonathan B.; Angelucci, Alessandra

doi: 10.1152/jn.00512.2009pmid: 19657084

Abstract In visual cortex, responses to stimulation of the receptive field (RF) are modulated by simultaneous stimulation of the RF surround. The mechanisms for surround modulation remain unidentified. We previously proposed that in the primary visual cortex (V1), near surround modulation is mediated by geniculocortical and horizontal connections and far surround modulation by interareal feedback connections. To understand spatial integration in the secondary visual cortex (V2) and its underlying circuitry, we have characterized spatial summation in different V2 layers and stripe compartments and compared it to that in V1. We used grating stimuli in circular and annular apertures of different sizes to estimate the extent and sensitivity of RF and surround components in V1 and V2. V2 RFs and surrounds were twice as large as those in V1. As in V1, V2 RFs doubled in size when measured at low contrast. In both V1 and V2, surrounds were about fivefold the size of the RF and the far surround could exceed 12.5° in radius, averaging 5.5° in V1 and 9.2° in V2. The strength of surround suppression was similar in both areas. Thus although differing in spatial scale, the interactions among RF components are similar in V1 and V2, suggesting similar underlying mechanisms. As in V1, the extent of V2 horizontal connections matches that of the RF center, but is much smaller than the largest far surrounds, which likely derive from interareal feedback. In V2, we found no laminar or stripe differences in size and magnitude of surround suppression, suggesting conservation across stripes of the basic circuit for surround modulation. Footnotes Copyright © 2009 The American Physiological Society

Praamstra, Peter; Kourtis, Dimitrios; Nazarpour, Kianoush

doi: 10.1152/jn.00413.2009pmid: 19657085

Abstract Neurophysiological studies in monkey have suggested that premotor and motor cortex may prepare for multiple movements simultaneously, sustained by cooperative and competitive interactions within and between the neural populations encoding different actions. Here, we investigate whether competition between alternative movement directions, manipulated in terms of number and spatial angle, is reflected in electroencephalographic (EEG) measures of (pre)motor cortical activity in humans. EEG was recorded during performance of a center-out pointing task in which response signals were preceded by cues providing prior information in the form of arrows pointing to one or more possible movement targets. Delay-period activity in (pre)motor cortex was modulated in the predicted manner by the number of possible movement directions and by the angle separating them. Response latencies, however, were determined not only by the amplitude of movement-preparatory activity, but also by differences in the duration of stimulus evaluation against the visuospatial memory of the cue, reflected in EEG potentials originating from posterior parietal cortex (PPC). Specifically, the spatial proximity of possible movement targets was processed differently by (pre)motor and posterior parietal cortex. Spatial proximity enhanced the amplitude of (pre)motor cortex preparatory activity during the delay period but delayed evaluation of the response signal in the PPC, thus producing opposite effects on response latency. The latter finding supports distributed control of movement decisions in the frontoparietal network, revealing a feature of distributed control that is of potential significance for the understanding of distracter effects in reaching and pointing. Footnotes Copyright © 2009 The American Physiological Society

Esser, Steve K.; Hill, Sean; Tononi, Giulio

doi: 10.1152/jn.00059.2009pmid: 19657080

Abstract Effective connectivity between cortical areas decreases during slow wave sleep. This decline can be observed in the reduced interareal propagation of activity evoked either directly in cortex by transcranial magnetic stimulation (TMS) or by sensory stimulation. We present here a large-scale model of the thalamocortical system that is capable of reproducing these experimental observations. This model was constructed according to a large number of physiological and anatomical constraints and includes over 30,000 spiking neurons interconnected by more than 5 million synaptic connections and organized into three cortical areas. By simulating the different effects of arousal promoting neuromodulators, the model can produce a waking or a slow wave sleep-like mode. In this work, we also seek to explain why intercortical signal transmission decreases in slow wave sleep. The traditional explanation for reduced brain responses during this state, a thalamic gate, cannot account for the reduced propagation between cortical areas. Therefore we propose that a cortical gate is responsible for this diminished intercortical propagation. We used our model to test three candidate mechanisms that might produce a cortical gate during slow wave sleep: a propensity to enter a local down state following perturbation, which blocks the propagation of activity to other areas, increases in potassium channel conductance that reduce neuronal responsiveness, and a shift in the balance of synaptic excitation and inhibition toward inhibition, which decreases network responses to perturbation. Of these mechanisms, we find that only a shift in the balance of synaptic excitation and inhibition can account for the observed in vivo response to direct cortical perturbation as well as many features of spontaneous sleep. Copyright © 2009 The American Physiological Society

Cothros, Nicholas; Wong, Jeremy; Gribble, Paul L.

doi: 10.1152/jn.00493.2009pmid: 19657075

Abstract Recent motor learning studies show that human subjects and nonhuman primates form neural representations of novel mechanical environments and associated forces. Whereas proficient adaptation is seen for a single force field, when faced with multiple novel force environments, movement performance and in particular the ability to switch between different force environments declines. It is difficult to reconcile these findings with the notion that primates can proficiently switch between multiple motor skills. Conceivably, particular kinds of sensory, cognitive, or perceptual contextual cues are required. This study examined the effect of visual feedback on motor learning, in particular, cues that simulated interaction with a virtual object. A robot arm was used to deliver novel patterns of forces (force fields) to the limb during reaching movements. We tested the possibility that subjects transition more easily between novel forces and their sudden absence when they are accompanied by visual cues that relate to object grasp. We used a virtual display system to present subjects with different kinds of visual feedback during reaching, including illusory feedback, indicating grasp of a virtual object during reaching in the force field, and object release in the absence of forces. Throughout the experiment, subjects in fact maintained grasp of the robot. We found that, indeed, the most effective visual cues were those associating the force field with grasp of the virtual object and the absence of the force field with release of the object. Our findings show more broadly that specific visual cues can protect motor skills from interference. Copyright © 2009 The American Physiological Society

Lapid, Hadas; Seo, Han-Seok; Schuster, Benno; Schneidman, Elad; Roth, Yehudah; Harel, David; Sobel, Noam; Hummel, Thomas

doi: 10.1152/jn.91321.2008pmid: 19657081

Abstract Electroolfactograms (EOGs) are the summated generator potentials of olfactory receptor neurons measured directly from the olfactory epithelium. To validate the sensory origin of the human EOG, we set out to ask whether EOGs measured in humans were odorant concentration dependent. Each of 22 subjects (12 women, mean age = 23.3 yr) was tested with two odorants, either valeric acid and linalool ( n = 12) or isovaleric acid and l -carvone ( n = 10), each delivered at four concentrations diluted with warm (37°C) and humidified (80%) odorless air. In behavior, increased odorant concentration was associated with increased perceived intensity (all F > 5, all P < 0.001). In EOG, increased odorant concentration was associated with increased area under the EOG curve (all F > 8, all P < 0.001). These findings substantiate EOG as a tool for probing olfactory coding directly at the level of olfactory receptor neurons in humans. Footnotes Copyright © 2009 The American Physiological Society