Journal of Neurophysiology

Pasupathy, Anitha; Connor, Charles E.

doi: N/Apmid: 10561421

Abstract The ventral pathway in visual cortex is responsible for the perception of shape. Area V4 is an important intermediate stage in this pathway, and provides the major input to the final stages in inferotemporal cortex. The role of V4 in processing shape information is not yet clear. We studied V4 responses to contour features (angles and curves), which many theorists have proposed as intermediate shape primitives. We used a large parametric set of contour features to test the responses of 152 V4 cells in two awake macaque monkeys. Most cells responded better to contour features than to edges or bars, and about one-third exhibited systematic tuning for contour features. In particular, many cells were selective for contour feature orientation, responding to angles and curves pointing in a particular direction. There was a strong bias toward convex (as opposed to concave) features, implying a neural basis for the well-known perceptual dominance of convexity. Our results suggest that V4 processes information about contour features as a step toward complex shape recognition. Footnotes Address for reprint requests: C. E. Connor, Zanvyl Krieger Mind/Brain Institute, Johns Hopkins University, 338 Krieger Hall, 3400 N. Charles St., Baltimore, MD 21218. The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “ advertisement ” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. Copyright © 1999 The American Physiological Society

Chiang, Chen Yu; Kwan, Chun L.; Hu, James W.; Sessle, Barry J.

doi: N/Apmid: 10561395

Abstract We have recently demonstrated that significant increases in cutaneous mechanoreceptive field (RF) size and spontaneous activity occur in nociceptive neurons of trigeminal subnucleus caudalis (Vc, the medullary dorsal horn) of adult rats depleted of C-fiber afferents by neonatal treatment with capsaicin. These neuronal changes in capsaicin-treated (CAP) rats are suggestive of central neuroplasticity and involve N -methyl- d -aspartic acid (NMDA) receptor mechanisms. The present study examined whether the GABA A receptor antagonist bicuculline (BIC) or the GABA B receptor antagonist 2-hydroxysaclofen (SAC) can influence the RF properties and activity of Vc nociceptive neurons classified as either nociceptive-specific or wide-dynamic range in CAP adult rats or in neonatally vehicle-treated (CON) rats. C-fiber depletion was confirmed in the CAP rats by a significant decrease in plasma extravasation of Evans blue dye in a skin area receiving topical application of mustard oil, a small-fiber excitant and inflammatory irritant. As previously reported, marked increases in cutaneous RF size and spontaneous activity occurred in Vc nociceptive neurons of adult CAP rats, compared with CON rats. GABA A receptor blockade by BIC (i.t.) in CON rats produced a significant increase in spontaneous activity and in pinch RF size and tactile RF size (or appearance of a tactile area in the RF of nociceptive-specific neurons), as well as a significant lowering of the mechanical threshold and a significant enhancement of responses to pinch stimuli applied to the RF. In CAP rats, GABA A receptor blockade also produced significant changes similar to those documented in CON rats, except for a paradoxical and significant decrease in pinch RF size and no noticeable changes in responses to pinch stimuli. GABA B receptor blockade by SAC (i.t.) did not produce any significant changes in Vc nociceptive neurons in either CON or CAP rats. These results suggest that GABA A receptor–mediated inhibition may be involved in maintaining the functional expression of Vc nociceptive neuronal properties in normal conditions, and that in animals depleted of their C-fiber afferents, some features of this GABA A receptor–mediated modulation may be disrupted such that a GABA A receptor–mediated excitation is manifested. Footnotes Address for reprint requests: B. J. Sessle, Faculty of Dentistry, University of Toronto, 124 Edward St., Toronto, Ontario M5G 1G6, Canada. The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “ advertisement ” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. Copyright © 1999 The American Physiological Society

Morishita, Wade; Alger, Bradley E.

doi: N/Apmid: 10561426

Abstract Depolarization-induced suppression of inhibition (DSI) is a process whereby brief ∼1-s depolarization to the postsynaptic membrane of hippocampal CA1 pyramidal cells results in a transient suppression of GABA A ergic synaptic transmission. DSI is triggered by a postsynaptic rise in Ca 2+ in and yet is expressed presynaptically, which implies that a retrograde signal is involved. Recent evidence based on synthetic metabotropic glutamate receptor (mGluR) agonists and antagonists suggested that group I mGluRs take part in the expression of DSI and raised the possibility that glutamate or a glutamate-like substance is the retrograde messenger in hippocampal CA1. This hypothesis was tested, and it was found that the endogenous amino acids l -glutamate ( l -Glu) and l- cysteine sulfinic acid ( l- CSA) suppressed GABA A -receptor–mediated inhibitory postsynaptic currents (IPSCs) and occluded DSI, whereas l- homocysteic acid ( l- HCA) and l- homocysteine sulfinic acid ( l- HCSA) did not. Activation of metabotropic kainate receptors with kainic acid (KA) reduced IPSCs; however, DSI was not occluded. When iontophoretically applied, both l- Glu and l- CSA produced a transient IPSC suppression similar in magnitude and time course to that observed during DSI. Both DSI and the actions of the amino acids were antagonized by (S)-α-methyl-4-carboxyphenylglycine (S-MCPG), indicating that the effects of the endogenous agonists were produced through activation of mGluRs. Blocking excitatory amino acid transport significantly increased DSI and the suppression produced by l- Glu or l- CSA without affecting the time constant of recovery from the suppression. Similar to DSI, IPSC suppression by l- Glu or l- CSA was blocked by N -ethylmaleimide (NEM). Moreover, paired-pulse depression (PPD), which is unaltered during DSI, is also not significantly affected by the amino acids. Taken together, these results support the glutamate hypothesis of DSI and argue that l- Glu or l- CSA are potential retrograde messengers in CA1. Footnotes Address for reprint requests: B. E. Alger, Dept. of Physiology, University of Maryland School of Medicine, 655 W. Baltimore St., Baltimore, MD 21201. The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “ advertisement ” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. Copyright © 1999 The American Physiological Society

Medendorp, W. P.; van Gisbergen, J.A.M.; Horstink, M.W.I.M.; Gielen, C.C.A.M.

doi: N/Apmid: 10561451

Abstract We investigated head movements of patients with spasmodic torticollis toward targets in various directions. These patients, whose severe dystonia was reflected in an abnormal resting head position, appeared to retain a Donders'-type strategy for the control of the rotational degrees of freedom of the head. As in normals, rotation vectors, representing head orientation, were confined to a curved surface, which specifies how head torsion depends on gaze direction. The orientation of the surface in body coordinates, which was very stereotyped in normals, was different for patients. The same Donders surface was found for head movements and for stationary head postures, indicating that the same neural mechanism governs its implementation in both tasks. To interpret our results, we propose a conceptual scheme incorporating the basal ganglia, which are thought to be involved in the etiology of torticollis, and an implementation stage for Donders' law. Footnotes Address for reprint requests: W. P. Medendorp, Dept. of Medical Physics and Biophysics, University of Nijmegen, Geert Grooteplein 21, NL 6525 EZ Nijmegen, The Netherlands. The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “ advertisement ” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. Copyright © 1999 The American Physiological Society

Sylvestre, Pierre A.; Cullen, Kathleen E.

doi: N/Apmid: 10561431

Abstract The mechanics of the eyeball and its surrounding tissues, which together form the oculomotor plant, have been shown to be the same for smooth pursuit and saccadic eye movements. Hence it was postulated that similar signals would be carried by motoneurons during slow and rapid eye movements. In the present study, we directly addressed this proposal by determining which eye movement–based models best describe the discharge dynamics of primate abducens neurons during a variety of eye movement behaviors. We first characterized abducens neuron spike trains, as has been classically done, during fixation and sinusoidal smooth pursuit. We then systematically analyzed the discharge dynamics of abducens neurons during and following saccades, during step-ramp pursuit and during high velocity slow-phase vestibular nystagmus. We found that the commonly utilized first-order description of abducens neuron firing rates (FR = b + k E + r E˙, where FR is firing rate, E and E˙ are eye position and velocity, respectively, and b , k, and r are constants) provided an adequate model of neuronal activity during saccades, smooth pursuit, and slow phase vestibular nystagmus. However, the use of a second-order model, which included an exponentially decaying term or “slide” (FR = b + k E + r E˙ + u Ë − c ), notably improved our ability to describe neuronal activity when the eye was moving and also enabled us to model abducens neuron discharges during the postsaccadic interval. We also found that, for a given model, a single set of parameters could not be used to describe neuronal firing rates during both slow and rapid eye movements. Specifically, the eye velocity and position coefficients ( r and k in the above models, respectively) consistently decreased as a function of the mean (and peak) eye velocity that was generated. In contrast, the bias ( b , firing rate when looking straight ahead) invariably increased with eye velocity. Although these trends are likely to reflect, in part, nonlinearities that are intrinsic to the extraocular muscles, we propose that these results can also be explained by considering the time-varying resistance to movement that is generated by the antagonist muscle. We conclude that to create realistic and meaningful models of the neural control of horizontal eye movements, it is essential to consider the activation of the antagonist, as well as agonist motoneuron pools. Footnotes Address for reprint requests: K. E. Cullen, 3655 Drummond St., Rm. 1220, Montreal, Quebec, Canada. The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “ advertisement ” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. Copyright © 1999 The American Physiological Society

Ahlfors, S. P.; Simpson, G. V.; Dale, A. M.; Belliveau, J. W.; Liu, A. K.; Korvenoja, A.; Virtanen, J.; Huotilainen, M.; Tootell, R.B.H.; Aronen, H. J.; Ilmoniemi, R. J.

doi: N/Apmid: 10561425

Abstract A sudden change in the direction of motion is a particularly salient and relevant feature of visual information. Extensive research has identified cortical areas responsive to visual motion and characterized their sensitivity to different features of motion, such as directional specificity. However, relatively little is known about responses to sudden changes in direction. Electrophysiological data from animals and functional imaging data from humans suggest a number of brain areas responsive to motion, presumably working as a network. Temporal patterns of activity allow the same network to process information in different ways. The present study in humans sought to determine which motion-sensitive areas are involved in processing changes in the direction of motion and to characterize the temporal patterns of processing within this network of brain regions. To accomplish this, we used both magnetoencephalography (MEG) and functional magnetic resonance imaging (fMRI). The fMRI data were used as supplementary information in the localization of MEG sources. The change in the direction of visual motion was found to activate a number of areas, each displaying a different temporal behavior. The fMRI revealed motion-related activity in areas MT+ (the human homologue of monkey middle temporal area and possibly also other motion sensitive areas next to MT), a region near the posterior end of the superior temporal sulcus (pSTS), V3A, and V1/V2. The MEG data suggested additional frontal sources. An equivalent dipole model for the generators of MEG signals indicated activity in MT+, starting at 130 ms and peaking at 170 ms after the reversal of the direction of motion, and then again at ∼260 ms. Frontal activity began 0–20 ms later than in MT+, and peaked ∼180 ms. Both pSTS and FEF+ showed long-duration activity continuing over the latency range of 200–400 ms. MEG responses in the region of V3A and V1/V2 were relatively small, and peaked at longer latencies than the initial peak in MT+. These data revealed characteristic patterns of activity in this cortical network for processing sudden changes in the direction of visual motion. Footnotes Address for reprint requests: S. P. Ahlfors, Rose F. Kennedy Center, Room 915, Albert Einstein College of Medicine, 1300 Morris Park Ave., Bronx, NY 10461. The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “ advertisement ” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. Copyright © 1999 The American Physiological Society

Parsons, Carl H.; Lanyon, Richard G.; Schnupp, Jan W. H.; King, Andrew J.

doi: N/Apmid: 10561407

Abstract We investigated the behavioral consequences of removing the pinna and concha of the external ear bilaterally in infancy on the sound localization ability of adult ferrets. Altering spectral cues in this manner has previously been shown to disrupt the development of the neural representation of auditory space in the superior colliculus. Using broadband noise stimuli, we tested pinnae-removed ferrets and normal ferrets in three sound localization tasks. In each case, we found that both groups of animals performed significantly better when longer duration noise bursts were used. In a relative localization task, we measured the acuity with which the ferrets could discriminate between two speakers in the horizontal plane. The speakers were placed symmetrically either around the anterior midline or around a position 45° lateral to the midline. In this task, the pinnae-removed ferrets achieved very similar scores to the normal ferrets. By contrast, in another relative localization task that measured localization ability in the midsagittal plane, pinnae-removed ferrets performed less well than normals. In an absolute localization task, 12 speakers were spaced at 30° intervals in the horizontal plane at the level of the ferrets' ears. Overall, the pinnae-removed ferrets also performed poorly in this task compared with normal ferrets: they made significantly fewer correct responses, larger localization errors and more front-back errors. Both normal and pinnae-removed animals showed an improvement in performance with practice, although the pattern of improvement differed for each group. The largest improvements in localization accuracy were achieved by the pinnae-removed ferrets, particularly at the frontal positions, and their performance eventually approached that of the normal animals. Nevertheless, some intergroup differences were still present. In particular, the pinnae-removed ferrets continued to make significantly more front-back errors than the normals. These deficits can be attributed to differences in the spectral localization cues available to the animals. Acoustical measurements showed that, compared with normal animals, the head-related transfer functions in the horizontal plane were largely ambiguous around the interaural axis and also contained fewer location-dependent features in the midsagittal plane. Footnotes Address for reprint requests: C. H. Parsons, University Laboratory of Physiology, Parks Road, Oxford OX1 3PT, UK. The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “ advertisement ” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. Copyright © 1999 The American Physiological Society

Kitama, Toshihiro; Omata, Tomohiro; Mizukoshi, Akihito; Ueno, Takehiko; Sato, Yu

doi: N/Apmid: 10561402

Abstract We investigated the relationship between eye movement and simple-spike (SS) frequency of Purkinje cells in the cerebellar flocculus middle zone during the optokinetic response (OKR) in alert cats. The OKR was elicited by a sequence of a constant-speed visual pattern movement in one direction for 1 s and then in the opposite direction for 1 s. Quick-phase-free trials were selected. Sixty-six cells had direction-selective complex spike (CS) activity that was modulated during horizontal (preferring contraversive) but not vertical stimuli. The SS activity was modulated during horizontal OKR, preferring ipsiversive stimuli. Forty-one cells had well-modulated activity and were suitable for the regression model. In these cells, an inverse dynamics approach was applied, and the time course of the SS rate was reconstructed, with mean coefficient of determination 0.76, by a linear weighted superposition of the eye acceleration (mean coefficient, 0.056 spikes/s per deg/s 2 ), velocity (5.10 spikes/s per deg/s), position (−2.40 spikes/s per deg), and constant (mean 34.3 spikes/s) terms, using a time delay (mean 11 ms) from the unit response to the eye response. The velocity and acceleration terms contributed to the increase in the reconstructed SS rates during ipsilateral movements, whereas the position term contributed during contralateral movements. The standard regression coefficient analyses revealed that the contribution of the velocity term (mean coefficient 0.81) was predominant over the acceleration (0.03) and position (−0.17) terms. Forward selection analysis revealed three cell types: Velocity-Position-Acceleration type ( n = 27): velocity, position, and acceleration terms are significant ( P < 0.05); Velocity-Position type ( n = 12): velocity and position terms are significant; and Velocity-Acceleration type ( n = 2): velocity and acceleration terms are significant. Using the set of coefficients obtained by regression of the response to a 5 deg/s stimulus velocity, the SS rates during higher (10, 20, and 40 deg/s) stimulus velocities were successfully reconstructed, suggesting generality of the model. The eye-position information encoded in the SS firing during the OKR was relative but not absolute in the sense that the magnitude of the position shift from the initial eye position (0 deg/s velocity) contributed to firing rate changes, but the initial eye position did not. It is concluded that 1 ) the SS firing frequency in the cat middle zone encodes the velocity and acceleration information for counteracting the viscosity and inertia forces respectively, during short-duration horizontal OKR and 2 ) the apparent position information encoded in the SS firing is not appropriate for counteracting the elastic force during the OKR. Footnotes Address reprint requests to Y. Sato. The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “ advertisement ” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. Copyright © 1999 The American Physiological Society

Lenz, F. A.; Jaeger, C. J.; Seike, M. S.; Lin, Y. C.; Reich, S. G.; DeLong, M. R.; Vitek, J. L.

doi: N/Apmid: 10561412

Abstract Indirect evidence suggests that the thalamus contributes to abnormal movements occurring in patients with dystonia (dystonia patients). The present study tested the hypothesis that thalamic activity contributes to the dystonic movements that occur in such patients. During these movements, spectral analysis of electromyographic (EMG) signals in flexor and extensor muscles of the wrist and elbow exhibited peak EMG power in the lowest frequency band 0–0.78 Hz (mean: 0.39 Hz) dystonia frequency for 60–85% of epochs studied during a pointing task. Normal controls showed low-frequency peaks for <16% of epochs during pointing. Among dystonia patients, simultaneous contraction of antagonistic muscles (cocontraction) at dystonia frequency during pointing was observed for muscles acting about the wrist (63% of epochs) and elbow (39%), but cocontraction was not observed among normal controls during pointing. Thalamic neuronal signals were recorded during thalamotomy for treatment of dystonia and were compared with those of control patients without motor abnormality who were undergoing thalamic procedures for treatment of chronic pain. Presumed nuclear boundaries of a human thalamic cerebellar relay nucleus (ventral intermediate, Vim) and a pallidal relay nucleus (ventral oral posterior, Vop) were estimated by aligning the anterior border of the principal sensory nucleus (ventral caudal, Vc) with the region where the majority of cells have cutaneous receptive fields (RFs). The ratio of power at dystonia frequency to average spectral power was >2 ( P < 0.001) for cells in presumed Vop often for dystonia patients (81%) but never for control patients. The percentage of such cells in presumed Vim of dystonia patients (32%) was not significantly different from that of controls (31%). Many cells in presumed Vop exhibited dystonia frequency activity that was correlated with and phase-advanced on EMG activity during dystonia, suggesting that this activity was related to dystonia. Thalamic somatic sensory activity also differed between dystonia patients and controls. The percentage of cells responding to passive joint movement or to manipulation of subcutaneous structures (deep sensory cells) in presumed Vim was significantly greater in patients with dystonia than in control patients undergoing surgery for treatment of pain or tremor. Dystonia patients had a significantly higher proportion of deep sensory cells responding to movement of more than one joint (26%, 13/52) than did “control” patients (8%, 4/49). Deep sensory cells in patients with dystonia were located in thalamic maps that demonstrated increased representations of parts of the body affected by dystonia. Thus dystonia patients showed increased receptive fields and an increased thalamic representation of dystonic body parts. The motor activity of an individual sensory cell was related to the sensory activity of that cell by identification of the muscle apparently involved in the cell's receptive field. Specifically, we defined the effector muscle as the muscle that, by contraction, produced the joint movement associated with a thalamic neuronal sensory discharge, when the examiner passively moved the joint. Spike X EMG correlation functions during dystonia indicated that thalamic cellular activity less often was related to EMG in effector muscles (52%) than in other muscles (86%). Thus there is a mismatch between the effector muscle for a thalamic cell and the muscles with EMG correlated with activity of that cell during dystonia. This mismatch may result from the reorganization of sensory maps and may contribute to the simultaneous activation of multiple muscles observed in dystonia. Microstimulation in presumed Vim in dystonia patients produced simultaneous contraction of multiple forearm muscles, similar to the simultaneous muscle contractions observed in dystonia. These observations are consistent with a model in which sensory input to Vim in dystonia is transmitted through altered sensory maps to activate multiple muscles in the periphery, producing the overflow of muscle activation that is characteristic of dystonia. Footnotes Address for reprint requests: F. A. Lenz, Dept. of Neurosurgery, Meyer Bldg. 7-113, Johns Hopkins Hospital, 600 N. Wolfe St., Baltimore, MD 21287-7713. The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “ advertisement ” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. Copyright © 1999 The American Physiological Society

Telgkamp, Petra; Ramirez, Jan-Marino

doi: N/Apmid: 10561396

Abstract The response of the neonatal respiratory system to hypoxia is characterized by an initial increase in ventilation, which is followed within a few minutes by a depression of ventilation below baseline levels. We used the transverse medullary slice of newborn mice as a model system for central respiratory control to investigate the effects of short-lasting periods of anoxia. Extracellular population activity was simultaneously recorded from the ventral respiratory group (VRG) and the hypoglossus (XII) nucleus (a respiration-related motor output nucleus). During anoxia, respiratory frequency was modulated in a biphasic manner and phase-locked in both the VRG and the XII. The amplitude of phasic respiratory bursts was increased only in the XII and not in the VRG. This increase in XII burst amplitude commenced ∼1 min after the anoxic onset concomitant with a transient increase in tonic activity. The burst amplitude remained elevated throughout the entire 5 min of anoxia. Inspiratory burst amplitude in the VRG, in contrary, remained constant or even decreased during anoxia. These findings represent the first simultaneous extracellular cell population recordings of two respiratory nuclei. They provide important data indicating that rhythm generation is altered in the VRG without a concomitant alteration in the VRG burst amplitude, whereas the burst amplitude is modulated only in the XII nucleus. This has important implications because it suggests that rhythm generation and motor pattern generation are regulated separately within the respiratory network. Footnotes Address for reprint requests: J.-M. Ramirez, Dept. of Organismal Biology and Anatomy, University of Chicago, 1027 E. 57th St., Chicago, IL 60637. The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “ advertisement ” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. Copyright © 1999 The American Physiological Society