Journal of Neurophysiology

Lajoie, Kim; Andujar, Jacques-Étienne; Pearson, Keir; Drew, Trevor

doi: 10.1152/jn.01100.2009pmid: 20164391

Abstract We tested the hypothesis that area 5 of the posterior parietal cortex (PPC) contributes to interlimb coordination in locomotor tasks requiring visual guidance by recording neuronal activity in this area in three cats in two locomotor paradigms. In the first paradigm, cats were required to step over obstacles attached to a moving treadmill belt. We recorded 47 neurons that discharged in relationship to the hindlimbs. Of these, 31/47 discharged between the passage of the fore- and hindlimbs (FL-HL cells) over the obstacle. The activity of most of these neurons (25/31) was related to the fore- and hindlimb contralateral to the recording site when the contralateral forelimb was the first to pass over the obstacle. In many cells, discharge activity was limb-independent in that it was better related to the ipsilateral limbs when they were the first to step over the obstacle. The other 16/47 neurons discharged only when the hindlimbs stepped over the obstacle with the majority of these (12/16) discharging between the passage of the two hindlimbs over the obstacle. We tested 15/47 cells, including 11/47 FL-HL cells, in a second paradigm in which cats stepped over an obstacle on a walkway. Discharge activity in all of these cells was significantly modulated when the cat stepped over the obstacle and remained modified for periods of ≤1 min when forward progress of the cat was delayed with either the fore- and hindlimbs, or the two hindlimbs, straddling the obstacle. We suggest that neurons in area 5 of the PPC contribute to interlimb coordination during locomotion by estimating the spatial and temporal attributes of the obstacle with respect to the body. We further suggest that the discharge observed both during the steps over the obstacle and in the delayed locomotor paradigm is a neuronal correlate of working memory. Copyright © 2010 the American Physiological Society

Linden, David J.

doi: 10.1152/jn.00168.2010pmid: 20164406

Schnupp, Jan W. H.; Bizley, Jennifer K.

doi: 10.1152/jn.00182.2010pmid: 20164385

Dai, Yue; Jordan, Larry M.

doi: 10.1152/jn.01111.2009pmid: 20164390

Abstract Using CFos-EGFP transgenic mice (P6–P12), we targeted persistent inward current (PIC) in the spinal interneurons activated by locomotion. Following a locomotor task, whole cell patch-clamp recordings were obtained from ventral EGFP + neurons in spinal cord slices (200–250 μm from T 13 –L 4 ). PIC was recorded by a family of 10 s voltage bi-ramps starting from −70 mV with 30 mV steps. PIC could be classified as ascending and descending forms based on the rising and falling phases of the bi-ramps. Multiple patterns of PIC with various hystereses were found in EGFP + neurons. A novel form of PIC, single PIC crossing both phases of the bi-ramps, was described in this study. PIC was found in 82% of EGFP + neurons ( n = 129) with no significant difference in laminar distribution. PIC activated at −56.7 ± 8 mV with an amplitude of 85.3 ± 59 pA and time constant of 657.0 ± 272 ms ( n = 63). PIC in lamina VIII neurons activated significantly lower (−60.2 ± 7 mV) than in lamina VII (−54.8 ± 6 mV) and lamina X (−55.8 ± 9 mV) neurons. PIC could be differentiated as calcium dependent (Ca-PIC) by bath application of 1–5 μM TTX or sodium dependent (Na-PIC) by administration of 20–30 μM dihydropyridine. Ca-PIC activated at −40.2 ± 19 mV ( n = 49), whereas Na-PIC activated at −46.8 ± 16 mV ( n = 17). Composite-, Ca-, and Na-PICs were significantly different in activation but not amplitude and time constant. Bath application of 5-HT (10–30 μM) enhanced PIC ( n = 32) by hyperpolarizing onset (4.2 ± 6 mV) and increasing amplitude (16%). 5-HT–increased amplitude seemed to be significantly larger in lamina VII neurons (32%) than VIII (6%) and X (14%) neurons. 5-HT enhancement of Ca-PIC ( n = 6) and Na-PICs ( n = 4) was also observed in EGFP + neurons. This study unveiled unique properties of PICs in EGFP + neurons. The lamina-related PIC activation and variable effects of 5-HT on PIC amplitude provides insight into the ionic basis on which locomotion could be generated. Copyright © 2010 the American Physiological Society

Lee, Sang-Hun; Govindaiah, G.; Cox, Charles L.

doi: 10.1152/jn.00540.2009pmid: 20107128

Abstract The thalamic reticular nucleus (TRN) consists of GABA-containing neurons that form reciprocal synaptic connections with thalamic relay nuclei. Excitatory synaptic innervation of TRN neurons arises from glutamatergic afferents from thalamocortical relay neurons and deep layer corticothalamic neurons, and they produce excitation via both N -methyl- d -aspartate (NMDA) and non-NMDA receptors. Quinoxaline derivatives e.g., 6,7-dinitroquinoxaline-2,3-dione (DNQX), 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) have routinely been used as non-NMDA receptor antagonists over the last two decades. In this study, we examined whether quinoxaline derivatives alter the intrinsic properties of thalamic neurons in light of recent findings indicating that these compounds can alter neuronal excitability in hippocampal and cerebellar neurons via transmembrane AMPA receptor (AMPAR) regulatory proteins (TARPs). Whole cell recordings were obtained from TRN and ventrobasal (VB) thalamic relay neurons in vitro. DNQX and CNQX produced a consistent depolarization in all TRN neurons tested. The depolarization persisted in tetrodotoxin and low Ca 2+ /high Mg 2+ conditions, suggesting a postsynaptic site of action. In contrast, DNQX and CNQX produced little or no change in VB thalamocortical relay neurons. The nonspecific ionotropic glutamate receptor antagonist, kynurenic acid, and the selective AMPAR antagonist, 4-(8-methyl-9H-1,3-dioxolo4,5-h2,3benzodiazepin-5-y l)-benzenamine hydrochloride, blocked the DNQX-mediated depolarizations. Our results indicate that the DNQX- and CNQX-mediated depolarizations are mediated by AMPAR but not kainate receptors in TRN neurons. The AMPAR-positive allosteric modulator, trichloromethiazide, potentiated the DNQX-mediated depolarization in TRN neurons but did not unmask any excitatory actions of DNQX/CNQX in relay neurons. This selective action may not only reveal a differential TARP distribution among thalamic neurons but also may provide insight into distinct characteristics of AMPA receptors of thalamic neurons that could be exploited by future pharmacological development. Furthermore, these data suggest that quinoxaline derivatives could modulate synaptic transmission and alter neuronal excitability. Footnotes Copyright © 2010 The American Physiological Society

Monte-Silva, Katia; Kuo, Min-Fang; Liebetanz, David; Paulus, Walter; Nitsche, Michael A.

doi: 10.1152/jn.00924.2009pmid: 20107115

Abstract Transcranial DC stimulation (tDCS) is a plasticity-inducing noninvasive brain stimulation tool with various potential therapeutic applications in neurological and psychiatric diseases. Currently, the duration of the aftereffects of stimulation is restricted. For future clinical applications, stimulation protocols are required that produce aftereffects lasting for days or weeks. Options to prolong the effects of tDCS are further prolongation or repetition of tDCS. Nothing is known thus far about optimal protocols in this behalf, although repetitive stimulation is already performed in clinical applications. Thus we explored the effects of different break durations on cathodal tDCS-induced cortical excitability alterations. In 12 subjects, two identical periods of cathodal tDCS (9-min duration; 1 mA) with an interstimulation interval of 0 (no break), 3, or 20 min or 3 or 24 h were performed. The results indicate that doubling stimulation duration without a break prolongs the aftereffects from 60 to 90 min after tDCS. When the second stimulation was performed during the aftereffects of the first, a prolongation and enhancement of tDCS-induced effects for ≤120 min after stimulation was observed. In contrast, when the second stimulation followed the first one after 3 or 24 h, the aftereffects were initially attenuated, or abolished, but afterwards re-established for up to 120 min after tDCS in the 24-h condition. These results suggest that, for prolonging the aftereffects of cathodal tDCS, stimulation interval might be important. Footnotes Copyright © 2010 the American Physiological Society

Trulsson, M.; Essick, G. K.

doi: 10.1152/jn.01146.2009pmid: 20130037

Abstract Intraneural microneurography and microstimulation were performed on single afferent axons in the inferior alveolar and lingual nerves innervating the face, teeth, labial, or oral mucosa. Using natural mechanical stimuli, 35 single mechanoreceptive afferents were characterized with respect to unit type fast adapting type I (FA I), FA hair, slowly adapting type I and II (SA I and SA II), periodontal, and deep tongue units as well as size and shape of the receptive field. All afferents were subsequently microstimulated with pulse trains at 30 Hz lasting 1.0 s. Afferents recordings whose were stable thereafter were also tested with single pulses and pulse trains at 5 and 60 Hz. The results revealed that electrical stimulation of single FA I, FA hair, and SA I afferents from the orofacial region can evoke a percept that is spatially matched to the afferent's receptive field and consistent with the afferent's response properties as observed on natural mechanical stimulation. Stimulation of FA afferents typically evoked sensations that were vibratory in nature; whereas those of SA I afferents were felt as constant pressure. These afferents terminate superficially in the orofacial tissues and seem to have a particularly powerful access to perceptual levels. In contrast, microstimulation of single periodontal, SA II, and deep tongue afferents failed to evoke a sensation that matched the receptive field of the afferent. These afferents terminate more deeply in the tissues, are often active in the absence of external stimulation, and probably access perceptual levels only when multiple afferents are stimulated. It is suggested that the spontaneously active afferents that monitor tension in collagen fibers (SA II and periodontal afferents) may have the role to register the mechanical state of the soft tissues, which has been hypothesized to help maintain the body's representation in the central somatosensory system. Copyright © 2010 the American Physiological Society

Kozhemyakin, Maxim; Rajasekaran, Karthik; Kapur, Jaideep

doi: 10.1152/jn.00949.2009pmid: 20107127

Abstract Central cholinergic overstimulation results in prolonged seizures of status epilepticus in humans and experimental animals. Cellular mechanisms of underlying seizures caused by cholinergic stimulation remain uncertain, but enhanced glutamatergic transmission is a potential mechanism. Paraoxon, an organophosphate cholinesterase inhibitor, enhanced glutamatergic transmission on hippocampal granule cells synapses by increasing the frequency and amplitude of spontaneous excitatory postsynaptic currents (sEPSCs) in a concentration-dependent fashion. The amplitude of mEPSCs was not increased, which suggested the possibility of enhanced action potential-dependent release. Analysis of EPSCs evoked by minimal stimulation revealed reduced failures and increased amplitude of evoked responses. The ratio of amplitudes of EPSCs evoked by paired stimuli was also altered. The effect of paraoxon on glutamatergic transmission was blocked by the muscarinic antagonist atropine and partially mimicked by carbachol. The nicotinic receptor antagonist α -bungarotoxin did not block the effects of paraoxon; however, nicotine enhanced glutamatergic transmission. These studies suggested that cholinergic overstimulation enhances glutamatergic transmission by enhancing neurotransmitter release from presynaptic terminals. Copyright © 2010 the American Physiological Society

Sepulveda, Fernando J.; Bustos, Fernando J.; Inostroza, Eveling; Zúñiga, Felipe A.; Neve, Rachael L.; Montecino, Martin; van Zundert, Brigitte

doi: 10.1152/jn.00823.2009pmid: 20107120

Abstract N -methyl- d -aspartate receptors (NMDARs) are known to regulate axonal refinement and dendritic branching. However, because NMDARs are abundantly present as tri-heteromers (e.g., NR1/NR2A/NR2B) during development, the precise role of the individual subunits NR2A and NR2B in these processes has not been elucidated. Ventral spinal cord neurons (VSCNs) provide a unique opportunity to address this problem, because the expression of both NR2A and NR2B (but not NR1) is downregulated in culture. Exogenous NR2A or NR2B were introduced into these naturally NR2-null neurons at 4 DIV, and electrophysiological recordings at 11 DIV confirmed that synaptic NR1NR2A receptors and NR1NR2B receptors were formed, respectively. Analysis of the dendritic architecture showed that introduction of NR2B, but not NR2A, dramatically increased the number of secondary and tertiary dendritic branches of VSCNs. Whole cell patch-clamp recordings further indicated that the newly formed branches in NR2B-expressing neurons were able to establish functional synapses because the frequency of miniature AMPA-receptor synaptic currents was increased. Using previously described mutants, we also found that disruption of the interaction between NR2B and RasGRF1 dramatically impaired dendritic branch formation in VSCNs. The differential role of the NR2A and NR2B subunits and the requirement for RasGRF1 in regulating branch formation was corroborated in hippocampal cultures. We conclude that the association between NR1NR2B-receptors and RasGRF1 is needed for dendritic branch formation in VSCNs and hippocampal neurons in vitro. The dominated NR2A expression and the limited interactions of this subunit with the signaling protein RasGRF1 may contribute to the restricted dendritic arbor development in the adult CNS. Footnotes Copyright © 2010 The American Physiological Society

Breza, Joseph M.; Nikonov, Alexandre A.; Contreras, Robert J.

doi: 10.1152/jn.00785.2009pmid: 20107132

Abstract The purpose of this study was to investigate the role of response latency in discrimination of chemical stimuli by geniculate ganglion neurons in the rat. Accordingly, we recorded single-cell 5-s responses from geniculate ganglion neurons ( n = 47) simultaneously with stimulus-evoked summated potentials (electrogustogram; EGG) from the anterior tongue to signal when the stimulus contacted the lingual epithelium. Artificial saliva served as the rinse solution and solvent for all stimuli (0.5 M sucrose, 0.03−0.5 M NaCl, 0.01 M citric acid, and 0.02 M quinine hydrochloride (QHCl), 0.1 M KCl as well as for 0.1 M NaCl +1 μM benzamil. Cluster analysis separated neurons into four groups (sucrose specialists, NaCl specialists, NaCl/QHCl generalists and acid generalists). Artificial saliva elevated spontaneous firing rate and response frequency of all neurons. As a rule, geniculate ganglion neurons responded with the highest frequency and shortest latency to their best stimulus with acid generalist the only exception. For specialist neurons and NaCl/QHCl generalists, the average response latency to the best stimulus was two to four times shorter than the latency to secondary stimuli. For NaCl-specialist neurons, response frequency increased and response latency decreased systematically with increasing NaCl concentration; benzamil significantly decreased NaCl response frequency and increased response latency. Acid-generalist neurons had the highest spontaneous firing rate and were the only group that responded consistently to citric acid and KCl. For many acid generalists, a citric-acid-evoked inhibition preceded robust excitation. We conclude that response latency may be an informative coding signal for peripheral chemosensory neurons. Copyright © 2010 The American Physiological Society