Journal of Neurophysiology

Fuchs, Paul

doi: 10.1152/jn.90838.2008pmid: 18684898

Roussin, Andre T.; Di Lorenzo, Patricia M.

doi: 10.1152/jn.90823.2008pmid: 18684899

Pastor, M. A.; Vidaurre, C.; Fernández-Seara, M. A.; Villanueva, A.; Friston, K. J.

doi: 10.1152/jn.01156.2007pmid: 18684912

Induced oscillatory activity in the auditory cortex peaks at around 40 Hz in humans. Using regional cerebral blood flow and positron emission tomography we previously confirmed frequency-selective cortical responses to 40-Hz tones in auditory primary cortices and concomitant bilateral activation of the cerebellar hemispheres. In this study, using functional magnetic resonance imaging (fMRI) we estimated the influence of 40-Hz auditory stimulation on the coupling between auditory cortex and superior temporal sulcus (STS) and Crus II, using a dynamic causal model of the interactions between medial geniculate nuclei, auditory superior temporal gyrus (STG)/STS, and the cerebellar Crus II auditory region. Specifically, we tested the hypothesis that 40-Hz-selective responses in the cerebellar Crus II auditory region could be explained by frequency-specific enabling of interactions in the auditory cortico–cerebellar–thalamic loop. Our model comparison results suggest that input from auditory STG/STS to cerebellum is enhanced selectively at gamma-band frequencies around 40 Hz. Address for reprint requests and other correspondence: M. A. Pastor, Centre for Applied Medical Research, Department of the Neurosciences, University of Navarra School of Medicine, CUN, 31080 Pamplona, Spain (E-mail: [email protected] )

Hashmi, Javeria A.; Davis, Karen D.

doi: 10.1152/jn.90500.2008pmid: 18701756

Acute and chronic pains are characterized by a particular constellation of pain qualities, such as burning, aching, stinging, or sharp feelings. However, the temporal pattern of specific pain qualities and their relationship with pain and affect is not well understood. In addition, little is known about how the temperature time course of the stimulus impacts the temporal dynamics of pain qualities and the relationship between pain qualities. Therefore we applied two types of stimuli to the feet of 16 healthy subjects, each calibrated to evoke a similar pain magnitude (50/100): static stimulus held at constant intensity and dynamic stimulus increased in intensity in small steps. Stimulus runs consisted of three 30-s stimuli (either static or dynamic) with an interstimulus interval of 60 s. Continuous on-line ratings of pain, burning, sharp, stinging, cutting, and annoyance were obtained in separate runs, and the evoked responses were characterized by within-stimulus adaptation (early: 0- to 15-s peak vs. late: 25- to 40-s peak) and by their temporal properties (time to onset, peak, and end). The temporal profile of the burning sensation was similar to the pain and annoyance evoked by the static and dynamic stimuli. However, the sharp, stinging and cutting sensations attenuated in response to the static stimuli ( P < 0.01) but intensified along with pain and affect in response to the dynamic stimuli ( P < 0.05), whereas there was no attenuation in the evoked profiles of pain ( P = 0.61), annoyance ( P = 0.27), or burning quality ( P = 0.27). These data demonstrate that specific pain qualities with known differences in underlying mechanisms have distinct temporal dynamics that depend on the stimulus intensity dynamics. Address for reprint requests and other correspondence: K. D. Davis, Div. of Brain, Imaging and Behaviour—Systems Neuroscience, Toronto Western Research Institute, Toronto Western Hospital, University Health Network, Room MP14-306, 399 Bathurst St., Toronto, Ontario, Canada M5T 2S8 (E-mail: [email protected] )

Mongeon, Rebecca; Gleason, Michelle R.; Masino, Mark A.; Fetcho, Joseph R.; Mandel, Gail; Brehm, Paul; Dallman, Julia E.

doi: 10.1152/jn.90596.2008pmid: 18715895

Truncated escape responses characteristic of the zebrafish shocked mutant result from a defective glial glycine transporter (GlyT1). In homozygous GlyT1 mutants, irrigating brain ventricles with glycine-free solution rescues normal swimming. Conversely, elevating brain glycine levels restores motility defects. These experiments are consistent with previous studies that demonstrate regulation of global glycine levels in the CNS as a primary function of GlyT1. As GlyT1 mutants mature, their ability to mount an escape response naturally recovers. To understand the basis of this recovery, we assay synaptic transmission in primary spinal motor neurons by measuring stimulus-evoked postsynaptic potentials. At the peak of the motility defect, inhibitory synaptic potentials are both significantly larger and more prolonged indicating a prominent role for GlyT1 in shaping fast synaptic transmission. However, as GlyT1 mutants naturally regain their ability to swim, the amplitude of inhibitory potentials decreases to below wild-type levels. In parallel with diminishing synaptic potentials, the glycine concentration required to evoke the mutant motility defect increases 61-fold during behavioral recovery. Behavioral recovery is also mirrored by a reduction in the levels of both glycine receptor protein and transcript. These results suggest that increased CNS glycine tolerance and reduced glycine receptor expression in GlyT1 mutants reflect compensatory mechanisms for functional recovery from excess nervous system inhibition. Present address and address for reprint requests and other correspondence: J. E. Dallman, Dept. of Biology, 1301 Memorial Dr., University of Miami, Coral Gables, FL, 33124 (E-mail: [email protected] )

Wittig, John H.; Parsons, Thomas D.

doi: 10.1152/jn.90322.2008pmid: 18667546

Synaptic ribbons are classically associated with mediating indefatigable neurotransmitter release by sensory neurons that encode persistent stimuli. Yet when hair cells lack anchored ribbons, the temporal precision of vesicle fusion and auditory nerve discharges are degraded. A rarified statistical model predicted increasing precision of first-exocytosis latency with the number of readily releasable vesicles. We developed an experimentally constrained biophysical model to test the hypothesis that ribbons enable temporally precise exocytosis by increasing the readily releasable pool size. Simulations of calcium influx, buffered calcium diffusion, and synaptic vesicle exocytosis were stochastic (Monte Carlo) and yielded spatiotemporal distributions of vesicle fusion consistent with experimental measurements of exocytosis magnitude and first-spike latency of nerve fibers. No single vesicle could drive the auditory nerve with requisite precision, indicating a requirement for multiple readily releasable vesicles. However, plasmalemma-docked vesicles alone did not account for the nerve's precision—the synaptic ribbon was required to retain a pool of readily releasable vesicles sufficiently large to statistically ensure first-exocytosis latency was both short and reproducible. The model predicted that at least 16 readily releasable vesicles were necessary to match the nerve's precision and provided insight into interspecies differences in synaptic anatomy and physiology. We confirmed that ribbon-associated vesicles were required in disparate calcium buffer conditions, irrespective of the number of vesicles required to trigger an action potential. We conclude that one of the simplest functions ascribable to the ribbon—the ability to hold docked vesicles at an active zone—accounts for the synapse's temporal precision. Address for reprint requests and other correspondence: T. D. Parsons, University of Pennsylvania, School of Veterinary Medicine, 382 West Street Road, Kennett Square, PA 19348 (E-mail: [email protected] )

Zhang, Dongyang; Snyder, Abraham Z.; Fox, Michael D.; Sansbury, Mark W.; Shimony, Joshua S.; Raichle, Marcus E.

doi: 10.1152/jn.90463.2008pmid: 18701759

The brain is active even in the absence of explicit stimuli or overt responses. This activity is highly correlated within specific networks of the cerebral cortex when assessed with resting-state functional magnetic resonance imaging (fMRI) blood oxygen level–dependent (BOLD) imaging. The role of the thalamus in this intrinsic activity is unknown despite its critical role in the function of the cerebral cortex. Here we mapped correlations in resting-state activity between the human thalamus and the cerebral cortex in adult humans using fMRI BOLD imaging. Based on this functional measure of intrinsic brain activity we partitioned the thalamus into nuclear groups that correspond well with postmortem human histology and connectional anatomy inferred from nonhuman primates. This structure/function correspondence in resting-state activity was strongest between each cerebral hemisphere and its ipsilateral thalamus. However, each hemisphere was also strongly correlated with the contralateral thalamus, a pattern that is not attributable to known thalamocortical monosynaptic connections. These results extend our understanding of the intrinsic network organization of the human brain to the thalamus and highlight the potential of resting-state fMRI BOLD imaging to elucidate thalamocortical relationships. Address for reprint requests and other correspondence: D. Zhang, Washington University, Department of Radiology, Campus Box 8225, 510 South Kingshighway Blvd., St. Louis, MO 63110 (E-mail: [email protected] )

Segers, Lauren S.; Nuding, Sarah C.; Dick, Thomas E.; Shannon, Roger; Baekey, David M.; Solomon, Irene C.; Morris, Kendall F.; Lindsey, Bruce G.

doi: 10.1152/jn.90414.2008pmid: 18632881

Current models propose that a neuronal network in the ventrolateral medulla generates the basic respiratory rhythm and that this ventrolateral respiratory column (VRC) is profoundly influenced by the neurons of the pontine respiratory group (PRG). However, functional connectivity among PRG and VRC neurons is poorly understood. This study addressed four model-based hypotheses: 1 ) the respiratory modulation of PRG neuron populations reflects paucisynaptic actions of multiple VRC populations; 2 ) functional connections among PRG neurons shape and coordinate their respiratory-modulated activities; 3 ) the PRG acts on multiple VRC populations, contributing to phase-switching; and 4 ) neurons with no respiratory modulation located in close proximity to the VRC and PRG have widely distributed actions on respiratory-modulated cells. Two arrays of microelectrodes with individual depth adjustment were used to record sets of spike trains from a total of 145 PRG and 282 VRC neurons in 10 decerebrate, vagotomized, neuromuscularly blocked, ventilated cats. Data were evaluated for respiratory modulation with respect to efferent phrenic motoneuron activity and short-timescale correlations indicative of paucisynaptic functional connectivity using cross-correlation analysis and the "gravity" method. Correlogram features were found for 109 (3%) of the 3,218 pairs composed of a PRG and a VRC neuron, 126 (12%) of the 1,043 PRG–PRG pairs, and 319 (7%) of the 4,340 VRC–VRC neuron pairs evaluated. Correlation linkage maps generated for the data support our four motivating hypotheses and suggest network mechanisms for proposed modulatory functions of the PRG. Address for reprint requests and other correspondence: B. G. Lindsey, Department of Molecular Pharmacology and Physiology, School of Biomedical Sciences, University of South Florida College of Medicine, 12901 Bruce B. Downs Blvd., Tampa, FL 33612-4799 (E-mail: [email protected] )

Rybak, I. A.; O'Connor, R.; Ross, A.; Shevtsova, N. A.; Nuding, S. C.; Segers, L. S.; Shannon, R.; Dick, T. E.; Dunin-Barkowski, W. L.; Orem, J. M.; Solomon, I. C.; Morris, K. F.; Lindsey, B. G.

doi: 10.1152/jn.90416.2008pmid: 18650310

A large body of data suggests that the pontine respiratory group (PRG) is involved in respiratory phase-switching and the reconfiguration of the brain stem respiratory network. However, connectivity between the PRG and ventral respiratory column (VRC) in computational models has been largely ad hoc. We developed a network model with PRG-VRC connectivity inferred from coordinated in vivo experiments. Neurons were modeled in the "integrate-and-fire" style; some neurons had pacemaker properties derived from the model of Breen et al. We recapitulated earlier modeling results, including reproduction of activity profiles of different respiratory neurons and motor outputs, and their changes under different conditions (vagotomy, pontine lesions, etc.). The model also reproduced characteristic changes in neuronal and motor patterns observed in vivo during fictive cough and during hypoxia in non-rapid eye movement sleep. Our simulations suggested possible mechanisms for respiratory pattern reorganization during these behaviors. The model predicted that network- and pacemaker-generated rhythms could be co-expressed during the transition from gasping to eupnea, producing a combined "burst-ramp" pattern of phrenic discharges. To test this prediction, phrenic activity and multiple single neuron spike trains were monitored in vagotomized, decerebrate, immobilized, thoracotomized, and artificially ventilated cats during hypoxia and recovery. In most experiments, phrenic discharge patterns during recovery from hypoxia were similar to those predicted by the model. We conclude that under certain conditions, e.g., during recovery from severe brain hypoxia, components of a distributed network activity present during eupnea can be co-expressed with gasp patterns generated by a distinct, functionally "simplified" mechanism. Address for reprint requests and other correspondence: B. G. Lindsey, Dept. of Molecular Pharmacology and Physiology, School of Biomedical Sciences, College of Medicine, University of South Florida, 12901 Bruce B. Downs Blvd., Tampa, FL 33612 (E-mail: [email protected] )

Meier, Jeffrey D.; Aflalo, Tyson N.; Kastner, Sabine; Graziano, Michael S. A.

doi: 10.1152/jn.90531.2008pmid: 18684903

A traditional view of the human motor cortex is that it contains an overlapping sequence of body part representations from the tongue in a ventral location to the foot in a dorsal location. In this study, high-resolution functional MRI (1.5 x 1.5 x 2 mm) was used to examine the somatotopic map in the lateral motor cortex of humans, to determine whether it followed the traditional somatotopic order or whether it contained any violations of that somatotopic order. The arm and hand representation had a complex organization in which the arm was relatively emphasized in two areas: one dorsal and the other ventral to a region that emphasized the fingers. This violation of a traditional somatotopic order suggests that the motor cortex is not merely a map of the body but is topographically shaped by other influences, perhaps including correlations in the use of body parts in the motor repertoire. Address for reprint requests and other correspondence: M.S.A. Graziano, Dept. of Psychology, Green Hall, Princeton Univ., Princeton, NJ 08544 (E-mail: [email protected] )