Journal of Neurophysiology

Ghatpande, Ambarish S.

doi: 10.1152/jn.91146.2008pmid: 19004990

Abstract The computational role of the olfactory bulb remains a mystery after 60 yr of physiological research. Recently, Fantana and colleagues proposed a new model of bulb function based on sparse inhibitory connections between glomeruli, the functional units of the bulb, rather than the existing lateral inhibition model. I present a summary of their model here and its implications along with comparison to recent work in the very similar Drosophila olfactory system. Footnotes 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 © 2009 the American Physiological Society

Connelly, William M.; Baggott, Matthew J.

doi: 10.1152/jn.91054.2008pmid: 19004992

Abstract Endocannabinoids are lipid retrograde messengers that can be released by postsynaptic depolarization and/or activation of certain metabotropic receptors. We review a recent report that activation of metabotropic 5-HT2 receptors by endogenous serotonin induces the release of endocannabinoids in the olivary nucleus and suppresses glutamatergic input through a presynaptic action. This serotonin–endocannabinoid interaction has implications in the pathophysiology of pain and mental illness and raises the possibility that drugs targeting the 5-HT2 receptor may act by modulating endocannabinoid release. Footnotes 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 © 2009 the American Physiological Society

Karayannidou, A.; Zelenin, P. V.; Orlovsky, G. N.; Sirota, M. G.; Beloozerova, I. N.; Deliagina, T. G.

doi: 10.1152/jn.90934.2008pmid: 19004997

Abstract During free behaviors animals often experience lateral forces, such as collisions with obstacles or interactions with other animals. We studied postural reactions to lateral pulses of force (pushes) in the cat during standing and walking. During standing, a push applied to the hip region caused a lateral deviation of the caudal trunk, followed by a return to the initial position. The corrective hindlimb electromyographic (EMG) pattern included an initial wave of excitation in most extensors of the hindlimb contralateral to push and inhibition of those in the ipsilateral limb. In cats walking on a treadmill with only hindlimbs, application of force also caused lateral deviation of the caudal trunk, with subsequent return to the initial position. The type of corrective movement depended on the pulse timing relative to the step cycle. If the force was applied at the end of the stance phase of one of the limbs or during its swing phase, a lateral component appeared in the swing trajectory of this limb. The corrective step was directed either inward (when the corrective limb was ipsilateral to force application) or outward (when it was contralateral). The EMG pattern in the corrective limb was characterized by considerable modification of the hip abductor and adductor activity in the perturbed step. Thus the basic mechanisms for balance control in these two forms of behavior are different. They perform a redistribution of muscle activity between symmetrical limbs (in standing) and a reconfiguration of the base of support during a corrective lateral step (in walking). Footnotes 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 © 2009 the American Physiological Society

Hermann, Joachim; Grothe, Benedikt; Klug, Achim

doi: 10.1152/jn.90243.2008pmid: 18971300

Abstract We measured synaptic responses to complex stimulus trains in the calyx of Held and used the data to test how well several vesicle-release models could capture the observed dynamics. We tested stimulation protocols consisting of Poisson-distributed activity with periodically changing mean frequencies, trains with constant inter spike intervals, and stimulus trains derived from in vivo responses to natural sounds. All stimuli were embedded in chronic background activity attempting to imitate the naturally occurring spontaneous activity in the auditory brain stem. We found that already the most basic model variant produced very good results, exhibiting very high correlation coefficients between the experimental data and the model predictions. None of the more complex model variants, which incorporated receptor desensitization, synaptic facilitation, and double-exponential recovery from depression, showed improved data-prediction matching accuracy. These findings are in contrast to previous modeling work performed in nonchronically active synapses, where the inclusion of additional physiological parameters into the modeling process tended to result in models with higher accuracy. Our findings suggest that the functional state of chronically active calyces may differ from the functional state of silent calyces and that this functional state of chronically active synapses can be described in relatively simple terms. Footnotes 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 © 2009 the American Physiological Society

Williams, Elizabeth R.; Baker, Stuart N.

doi: 10.1152/jn.90362.2008pmid: 19019981

Abstract Recordings of motor cortical activity typically show oscillations around 10 and 20 Hz; only those at 20 Hz are coherent with electromyograms (EMGs) of contralateral muscles. Experimental measurements of the phase difference between approximately 20-Hz oscillations in cortex and muscle are often difficult to reconcile with the known corticomuscular conduction delays. We investigated the generation of corticomuscular coherence further using a biophysically based computational model, which included a pool of motoneurons connected to motor units that generated EMGs. Delays estimated from the coherence phase–frequency relationship were sensitive to the width of the motor unit action potentials. In addition, the nonlinear properties of the motoneurons could produce complex, oscillatory phase–frequency relationships. This was due to the interaction of cortical inputs to the motoneuron pool with the intrinsic rhythmicity of the motoneurons; the response appeared more linear if the firing rate of motoneurons varied widely across the pool, such as during a strong contraction. The model was able to reproduce the smaller than expected delays between cortex and muscles seen in experiments. However, the model could not reproduce the constant phase over a frequency band sometimes seen in experiments, nor the lack of around 10-Hz coherence. Simple propagation of oscillations from cortex to muscle thus cannot completely explain the observed corticomuscular coherence. Footnotes 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 © 2009 the American Physiological Society

Gu, Huaiyu; Jiang, Shaojuan Amy; Campusano, Jorge M.; Iniguez, Jorge; Su, Hailing; Hoang, Andy An; Lavian, Monica; Sun, Xicui; O'Dowd, Diane K.

doi: 10.1152/jn.91103.2008pmid: 19004991

Abstract Voltage-gated calcium channels containing α1 subunits encoded by Ca v 2 family genes are critical in regulating release of neurotransmitter at chemical synapses. In Drosophila , cac is the only Ca v 2-type gene. Cacophony (CAC) channels are localized in motor neuron terminals where they have been shown to mediate evoked, but not AP-independent, release of glutamate at the larval neuromuscular junction (NMJ). Cultured embryonic neurons also express CAC channels, but there is no information about the properties of CAC-mediated currents in adult brain nor how these channels regulate transmission in central neural circuits where fast excitatory synaptic transmission is predominantly cholinergic. Here we report that wild-type neurons cultured from late stage pupal brains and antennal lobe projection neurons (PNs) examined in adult brains, express calcium currents with two components: a slow-inactivating current sensitive to the spider toxin Plectreurys toxin II (PLTXII) and a fast-inactivating PLTXII-resistant component. CAC channels are the major contributors to the slow-inactivating PLTXII-sensitive current based on selective reduction of this component in hypomorphic cac mutants ( NT27 and TS3 ). Another characteristic of cac mutant neurons both in culture and in whole brain recordings is a reduced cholinergic miniature excitatory postsynaptic current frequency that is mimicked in wild-type neurons by acute application of PLTXII. These data demonstrate that cac encoded Ca v 2-type calcium channels regulate action potential (AP)-independent release of neurotransmitter at excitatory cholinergic synapses in the adult brain, a function not predicted from studies at the larval NMJ. Footnotes ↵ * H. Gu, S. A. Jiang, J. M. Campusano, and J. Iniguez contributed equally to this work. 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 © 2009 the American Physiological Society

Pfeiffer, Keram; Panek, Izabela; Höger, Ulli; French, Andrew S.; Torkkeli, Päivi H.

doi: 10.1152/jn.91020.2008pmid: 19004993

Abstract γ-Aminobutyric acid type A (GABA A ) receptor activation inhibits many primary afferent neurons by depolarization and increased membrane conductance. Deterministic (step and sinusoidal) functions are commonly used as stimuli to test such inhibition. We found that when the VS-3 mechanosensory neurons innervating the spider lyriform slit-sense organ were stimulated by randomly varying white-noise mechanical or electrical signals, their responses to GABA A receptor agonists were more complex than the inhibition observed during deterministic stimulation. Instead, there was rapid excitation, then brief inhibition, followed by long-lasting excitation. During the final excitatory phase, VS-3 neuron sensitivity to high-frequency signals increased selectively and their linear information capacity also increased. Using experimental and simulation approaches we found that the excitatory effect could also be achieved by depolarizing the neurons without GABA application and that excitation could override the inhibitory effect produced by increased membrane conductance (shunting). When the VS-3 neurons were exposed to bumetanide, an antagonist of the Cl − transporter NKCC1, the GABA-induced depolarization decreased without any change in firing rate, suggesting that the effects of GABA can be maintained for a long time without additional Cl − influx. Our results show that the VS-3 neuron's response to GABA depends profoundly on the type of signals the neuron is conveying while the transmitter binds to its receptors. Footnotes 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 © 2009 the American Physiological Society

Yan, Haidun; Li, Qiang; Fleming, Rebekah; Madison, Roger D.; Wilson, Wilkie A.; Swartzwelder, H. Scott

doi: 10.1152/jn.90557.2008pmid: 18971298

Abstract Ethanol (EtOH) has powerful effects on GABA A receptor-mediated neurotransmission, and we have previously shown that EtOH-induced enhancement of GABA A receptor-mediated synaptic transmission in the hippocampus is developmentally regulated. Because synaptic inhibition is determined in part by the firing properties of interneurons, we have investigated the mechanisms whereby EtOH influences the spontaneous firing characteristics and hyperpolarization-activated cation current ( I h ) of hippocampal interneurons located in the near to the border of stratum lacunosum moleculare and s. radiatum of adolescent and adult rats. EtOH did not affect current injection-induced action potentials of interneurons that do not exhibit spontaneous firing. However, in neurons that fire spontaneously, EtOH enhanced the frequency of spontaneous action potentials (sAPs) in a concentration-dependent manner, an effect that was more pronounced in interneurons from adolescent rats, compared with adult rats. EtOH also modulated the afterhyperpolarization (AHP) that follows sAPs by shortening the τ slow decay time constant, and this effect was more pronounced in slices from adolescent rats. EtOH increased I h amplitudes, accelerated I h activation kinetics, and increased the maximal I h conductance in interneurons from animals in both age groups. These effects were also more pronounced in interneurons from adolescents and persisted in the presence of glutamatergic and GABAergic blockers. However, EtOH failed to affect sAP firing in the presence of ZD7288 or cesium chloride. These results suggest that I h may be of mechanistic significance in the effect of EtOH on interneuron spontaneous firing. Footnotes 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 © 2009 the American Physiological Society

Geier, Charles F.; Garver, Krista; Terwilliger, Robert; Luna, Beatriz

doi: 10.1152/jn.90562.2008pmid: 18971297

Abstract The neural circuitry supporting mature visual spatial working memory (VSWM) has been well delineated in nonhuman primates and in human adults. However, we still have limited understanding about developmental change through adolescence in this network. We present results from a fast event-related functional MRI (fMRI) study aimed at characterizing developmental changes in brain mechanisms supporting VSWM across different delay periods. Forty-three healthy subjects (17 adults, 18–30 yr; 13 adolescents, 13–17 yr; 13 children, 8–12 yr) were scanned as they performed an oculomotor delayed response (ODR) task with short (2.5 s) and long (10 s) delay period trials. Results showed that all age groups recruited a common network of regions to support both delay trials, including frontal, parietal, and temporal regions, indicative of a core circuitry needed to perform the task. Several age-related differences were found in the recruitment of regions, supporting short delay trials, including fronto-caudal areas, which could contribute to known differences in initial memory-guided saccade precision. To support extended delay trials, adults primarily recruited additional posterior parietal cortex (PPC), whereas children and adolescents recruited a considerably more extensive distributed circuitry. Our findings indicate that brain processes supporting basic aspects of working memory across cortex are established by childhood. We also find evidence for continued immaturities in systems supporting working memory precision, reflected by differences in the circuitry recruited by children and by continued refinement of fronto-insular-temporal regions recruited by adolescents. Taken together, these results suggest distinct developmental changes in the circuitry supporting visual spatial working memory. Footnotes 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 © 2009 the American Physiological Society

Nieto-Gonzalez, Jose Luis; Carrascal, Livia; Nunez-Abades, Pedro; Torres, Blas

doi: 10.1152/jn.90239.2008pmid: 18971301

Abstract Above recruitment threshold, ocular motoneurons (Mns) show a firing rate linearly related with eye position. Current hypothesis suggests that synaptic inputs are determinant for establishing the recruitment threshold and firing rate gain in these Mns. We investigated this proposal by studying the cholinergic modulation in oculomotor nucleus Mns by intracellular recordings in rat brain slice preparation. All recorded Mns were silent at their resting membrane potential. Bath application of carbachol (10 μm) produced a depolarization and a sustained firing that was not silenced on returning membrane potential to the precarbachol value via DC injection. In response to similar membrane depolarization or equal-current steps, carbachol-exposed Mns produced a higher firing rate and a shorter spike afterhyperpolarization phase with lower amplitude. The relationship between injected current and firing rate ( I – F ) was linear in control and carbachol-exposed Mns. The slope of these relationships ( I – F gain) decreased with carbachol exposure. Bath application of agonist and antagonist of nicotinic and muscarinic acetylcholine receptors in addition to immunohistochemical studies support the notion that muscarinic receptors are primarily involved in the preceding responses. We conclude that muscarinic inputs play an important role in determining the recruitment threshold and firing rate gain observed in oculomotor Mns in vivo. Footnotes ↵ * These authors contributed equally to this work. 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 © 2009 the American Physiological Society