Journal of Neurophysiology

Mayo, J. Patrick

doi: 10.1152/jn.91369.2008pmid: 19144737

Abstract The classical model of visual processing emphasizes the lateral geniculate nucleus (LGN) as the major intermediary between the retina and visual cortex. Yet, anatomical findings inspired Francis Crick to suggest an alternative model in which the thalamic reticular nucleus, which envelops the LGN, acts as the “guardian” of visual cortex by modulating LGN activity. Recent work by McAlonan and colleagues supports Crick's hypothesis, thereby enhancing our understanding of the early stages of visual processing. 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

Grün, Sonja

doi: 10.1152/jn.00093.2008pmid: 19129298

Abstract The mechanisms underlying neuronal coding and, in particular, the role of temporal spike coordination are hotly debated. However, this debate is often confounded by an implicit discussion about the use of appropriate analysis methods. To avoid incorrect interpretation of data, the analysis of simultaneous spike trains for precise spike correlation needs to be properly adjusted to the features of the experimental spike trains. In particular, nonstationarity of the firing of individual neurons in time or across trials, a spike train structure deviating from Poisson, or a co-occurrence of such features in parallel spike trains are potent generators of false positives. Problems can be avoided by including these features in the null hypothesis of the significance test. In this context, the use of surrogate data becomes increasingly important, because the complexity of the data typically prevents analytical solutions. This review provides an overview of the potential obstacles in the correlation analysis of parallel spike data and possible routes to overcome them. The discussion is illustrated at every stage of the argument by referring to a specific analysis tool (the Unitary Events method). The conclusions, however, are of a general nature and hold for other analysis techniques. Thorough testing and calibration of analysis tools and the impact of potentially erroneous preprocessing stages are emphasized. 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

Kamendi, H. W.; Cheng, Q.; Dergacheva, O.; Gorini, C.; Jameson, H. S.; Wang, X.; McIntosh, J. M.; Mendelowitz, D.

doi: 10.1152/jn.90680.2008pmid: 19091927

Abstract Cardioinhibitory cardiac vagal neurons (CVNs) do not receive inspiratory-related excitatory inputs under normal conditions. However, excitatory purinergic and serotonergic pathways are recruited during inspiratory activity after episodes of hypoxia and hypercapnia (H/H). Prenatal nicotine (PNN) exposure is known to dramatically change cardiorespiratory responses and decrease the ability to resuscitate from H/H. This study tested whether PNN exposure alters excitatory neurotransmission to CVNs in the nucleus ambiguus during and after H/H. Spontaneous and inspiratory evoked excitatory postsynaptic currents were recorded in CVNs from rats that were exposed to nicotine (6 mg·kg −1 ·d −1 ) throughout the prenatal period. In contrast to unexposed animals, in PNN animals H/H recruited excitatory neurotransmission to CVNs during inspiratory-related activity that was blocked by the α3β4 nicotinic acetylcholine receptor (nAChR) blocker α-conotoxin AuIB (α-CTX AuIB, 100 μM) and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 50 μM) and d (−)-2-amino-5-phosphonopentanoic acid (AP5, 50 μM), selective AMPA/kainate and N -methyl- d -aspartate receptor blockers, respectively. Following H/H, there was a significant increase in inspiratory-related excitatory postsynaptic currents that were unaltered by α-CTX AuIB or ondansetron, a 5-HT3 receptor blocker, but were subsequently inhibited by pyridoxalphosphate-6-azophenyl-2′, 4′-disulphonic acid (100 μM), a purinergic receptor blocker and CNQX and AP5. The results from this study demonstrate that with PNN exposure, an excitatory neurotransmission to CVNs is recruited during H/H that is glutamatergic and dependent on activation of α3β4-containing nAChRs. Furthermore, exposure to PNN abolishes a serotonergic long-lasting inspiratory-related excitation of CVNs that is replaced by recruitment of a glutamatergic pathway to CVNs post H/H. 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

Pezier, A.; Bobkov, Y. V.; Ache, B. W.

doi: 10.1152/jn.90903.2008pmid: 19118110

Abstract The mechanism(s) of olfactory transduction in invertebrates remains to be fully understood. In lobster olfactory receptor neurons (ORNs), a nonselective sodium-gated cation (SGC) channel, a presumptive transient receptor potential (TRP)C channel homolog, plays a crucial role in olfactory transduction, at least in part by amplifying the primary transduction current. To better determine the functional role of the channel, it is important to selectively block the channel independently of other elements of the transduction cascade, causing us to search for specific pharmacological blockers of the SGC channel. Given evidence that the Na + /Ca 2+ exchange inhibitor, KB-R7943, blocks mammalian TRPC channels, we studied this probe as a potential blocker of the lobster SGC channel. KB-R7943 reversibly blocked the SGC current in both inside- and outside-out patch recordings in a dose- and voltage-dependent manner. KB-R7943 decreased the channel open probability without changing single channel amplitude. KB-R7943 also reversibly and in a dose-dependent manner inhibited both the odorant-evoked discharge of lobster ORNs and the odorant-evoked whole cell current. Our findings strongly imply that KB-R7943 potently blocks the lobster SGC channel and likely does so directly and not through its ability to block the Na + /Ca 2+ exchanger. 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

Middleton, Jason W.; Longtin, André; Benda, Jan; Maler, Leonard

doi: 10.1152/jn.90814.2008pmid: 19091925

Abstract Parallel sensory streams carrying distinct information about various stimulus properties have been observed in several sensory systems, including the visual system. What remains unclear is why some of these streams differ in the size of their receptive fields (RFs). In the electrosensory system, neurons with large RFs have short-latency responses and are tuned to high-frequency inputs. Conversely, neurons with small RFs are low-frequency tuned and exhibit longer-latency responses. What principle underlies this organization? We show experimentally that synchronous electroreceptor afferent (P-unit) spike trains selectively encode high-frequency stimulus information from broadband signals. This finding relies on a comparison of stimulus-spike output coherence using output trains obtained by either summing pairs of recorded afferent spike trains or selecting synchronous spike trains based on coincidence within a small time window. We propose a physiologically realistic decoding mechanism, based on postsynaptic RF size and postsynaptic output rate normalization that tunes target pyramidal cells in different electrosensory maps to low- or high-frequency signal components. By driving realistic neuron models with experimentally obtained P-unit spike trains, we show that a small RF is matched with a postsynaptic integration regime leading to responses over a broad range of frequencies, and a large RF with a fluctuation-driven regime that requires synchronous presynaptic input and therefore selectively encodes higher frequencies, confirming recent experimental data. Thus our work reveals that the frequency content of a broadband stimulus extracted by pyramidal cells, from P-unit afferents, depends on the amount of feedforward convergence they receive. 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

Cowley, Kristine C.; Zaporozhets, Eugene; Joundi, Raed A.; Schmidt, Brian J.

doi: 10.1152/jn.91212.2008pmid: 19118107

Abstract Commissural projections are required for left-right coordination during locomotion. However, their role, if any, in rhythm production is unknown. This study uses the neonatal rat in vitro brain stem–spinal cord model to examine the rostrocaudal distribution of locomotor-related commissural projections and study whether commissural connections are needed for the generation of hindlimb rhythmic activity in response to electrical stimulation of the brain stem. Midsagittal lesions were made at a wide range of rostrocaudal levels. Locomotor-like activity persisted in some preparations despite midsagittal lesions extending from C 1 to the mid-L 1 level or from the conus medullaris to the T 12/13 junction. In some preparations, midsagittal lesions throughout the entire spinal cord had no effect on locomotor-like activity if two or three contiguous segments remained intact. Those bridging segments had to include the T 13 and/or L 1 levels. These observations suggested that commissural projections in the thoracolumbar junction region were critical. However, locomotor-like activity was also elicited in preparations with limited midsagittal lesions focused on the thoracolumbar junction (T 12 through L 1 or L 2 inclusive). In other experiments, locomotor-like activity was evoked by bath-applied 5-hydroxytryptamine (5-HT) and N -methyl- d -aspartate (NMDA). Appropriate side-to-side coordination was observed, even when only one segment remained bilaterally intact. Commissural projections traversing the thoracolumbar junction region were most effective. In combination, these results suggest that locomotor-related commissural projections are redundantly distributed along a bi-directional gradient that centers on the thoracolumbar junction. This commissural system not only provides a robust left-right coordinating mechanism but also supports locomotor rhythm generation in response to brain stem stimulation. 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

Zarnowska, Ewa D.; Keist, Ruth; Rudolph, Uwe; Pearce, Robert A.

doi: 10.1152/jn.91203.2008pmid: 19073796

Abstract γ-Aminobutyric acid type A (GABA A ) receptor α5 subunits, which are heavily expressed in the hippocampus, are potential drug targets for improving cognitive function. They are found at synaptic and extrasynaptic sites and have been shown to mediate tonic inhibition in pyramidal neurons. We tested the hypothesis that α5 subunits also contribute to synaptic inhibition by measuring the effect of diazepam (DZ) on spontaneous and stimulus-evoked inhibitory postsynaptic currents (IPSCs) in genetically modified mice carrying a point mutation in the α5 subunit (α5-H105R) that renders those receptors insensitive to benzodiazepines. In wild type mice, DZ (1 μM) increased the amplitude of spontaneous IPSCs (sIPSCs) and stimulus-evoked GABA A,slow IPSCs (eIPSCs) and prolonged the decay of GABA A,fast sIPSCs. In α5-mutant mice, DZ increased the amplitude of a small-amplitude subset of sIPSCs (<50 pA) and eIPSCs (<300 pA) GABA A,slow and prolonged the decay of GABA A,fast sIPSCs, but failed to increase the amplitude of larger sIPSCs and eIPSCs GABA A,slow . These results indicate that α5 subunits contribute to a large-amplitude subset of GABA A,slow synapses and implicate these synapses in modulation of cognitive function by drugs that target α5 subunits. 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

Sabolek, Helen R.; Penley, Stephanie C.; Hinman, James R.; Bunce, Jamie G.; Markus, Etan J.; Escabi, Monty; Chrobak, James J.

doi: 10.1152/jn.90846.2008pmid: 19118111

Abstract Theta and gamma rhythms synchronize neurons within and across brain structures. Both rhythms are widespread within the hippocampus during exploratory behavior and rapid-eye-movement (REM) sleep. How synchronous are these rhythms throughout the hippocampus? The present study examined theta and gamma coherence along the septotemporal (long) axis of the hippocampus in rats during REM sleep, a behavioral state during which theta signals are unaffected by external sensory input or ongoing behavior. Unilateral entorhinal cortical inputs are thought to play a prominent role in the current generation of theta, whereas current generation of gamma is primarily due to local GABAergic neurons. The septal 50% (4–5 mm) of the dentate gyrus (DG) receives a highly divergent, unilateral projection from any focal point along a lateral band of entorhinal neurons near the rhinal sulcus. We hypothesized that theta coherence in the target zone (septal DG) of this divergent entorhinal input would not vary, while gamma coherence would significantly decline with distance in this zone. However, both theta and gamma coherence decreased significantly along the long axis in the septal 50% of the hippocampus across both DG and CA1 electrode sites. In contrast, theta coherence between homotypic (e.g., DG to DG) sites in the contralateral hemisphere (∼3–5 mm distant) were quite high (∼0.7–0.9), much greater than theta coherence between homotypic sites 3–5 mm distant (∼0.4–0.6) along the long axis. These findings define anatomic variation in both rhythms along the longitudinal axis of the hippocampus, indicate the bilateral CA3/mossy cell projections are the major determinant of theta coherence during REM, and demonstrate that theta coherence varies as a function of anatomical connectivity rather than physical distance. We suggest CA3 and entorhinal inputs interact dynamically to generate theta field potentials and advance the utility of theta and gamma coherence as indicators of hippocampal dynamics. 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

Kuo, Chung-Chih; Chiou, Ruei-Jen; Liang, Keng-Chen; Yen, Chen-Tung

doi: 10.1152/jn.90347.2008pmid: 19091928

Abstract The present study examined the role of neurons in different pain-related functions of the anterior cingulate cortex (ACC) and primary sensorimotor cortex (SmI) by assessing their abilities to code different levels of noxious heat and activity changes evoked by classical fear conditioning involving electric shocks. Multiple single-unit activity was recorded with microwires implanted in the SmI and ACC of each rat. In the first set of experiments, the middle segment of the tail in each rat was irradiated with laser-heat pulses of various intensities. Neuronal responses in both the SmI and ACC increased with the intensity of the laser heat, although there was a significantly higher percentage of intensity-related units in the SmI. Furthermore, the stimulus–response curve of SmI ensemble activity had a steeper slope than that of the ACC. In the second set of experiments, rats were trained and tested on a conditioned fear-potentiated startle task in which a light was paired with an electric shock and, later, the startle response was elicited by a burst of noise in the presence or absence of light. A higher percentage of ACC units changed their neuronal responses to the conditioned stimulus after the light–shock pairing and the average activity change was also significantly stronger. Our results suggest that SmI neurons are better at coding laser-heat intensity than ACC neurons, whereas more ACC neurons are involved in conditioned fear associated with an electric shock than SmI neurons. These data provide evidence for differential contributions of the SmI and ACC to sensory and affective dimensions of pain. 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

Sanchez, Antonio; Mustapic, Sanda; Zuperku, Edward J.; Stucke, Astrid G.; Hopp, Francis A.; Stuth, Eckehard A. E.

doi: 10.1152/jn.90279.2008pmid: 19091929

Abstract Hypoglossal motoneurons (HMNs) innervate all tongue muscles and are vital for maintenance of upper airway patency during inspiration. The relative contributions of the various synaptic inputs to the spontaneous discharge of HMNs in vivo are incompletely understood, especially at the cellular level. The purpose of this study was to determine the role of endogenously activated GABA A and glycine receptors in the control of the inspiratory HMN (IHMN) activity in a decerebrate dog model. Multibarrel micropipettes were used to record extracellular unit activity of individual IHMNs during local antagonism of GABA A receptors with bicuculline and picrotoxin or glycine receptors with strychnine. Only bicuculline had a significant effect on peak and average discharge frequency and on the slope of the augmenting neuronal discharge pattern. These parameters were increased by 30 ± 7% ( P < 0.001), 30 ± 8% ( P < 0.001), and 25 ± 7% ( P < 0.001), respectively. The effects of picrotoxin and strychnine on the spontaneous neuronal discharge and its pattern were negligible. Our data suggest that bicuculline-sensitive GABAergic, but not picrotoxin-sensitive GABAergic or glycinergic, inhibitory mechanisms actively attenuate the activity of IHMNs in vagotomized decerebrate dogs during hyperoxic hypercapnia. The pattern of GABAergic attenuation of IHMN discharge is characteristic of gain modulation similar to that in respiratory bulbospinal premotor neurons, but the degree of attenuation (∼25%) is less than that seen in bulbospinal premotor neurons (∼60%). The current studies only assess effects on active neuron discharge and do not resolve whether the lack of effect of picrotoxin and strychnine on IHMNs also extends to the inactive expiratory phase. 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