Differential Contributions of Thalamic Nuclei in the Generation of AntisaccadesCameron, Ian G. M.; Watanabe, Masayuki
doi: 10.1152/jn.00603.2010pmid: 20739592
Abstract Our knowledge of thalamus function comes largely from anatomical studies showing, for example, that the ventroanterior (VA) and ventrolateral (VL) nuclei are connected to “motor” regions, whereas the mediodorsal (MD) nucleus is connected to prefrontal “executive” regions. Interestingly, Kunimatsu and Tanaka recently showed that preparatory signals for antisaccades (a motor response requiring executive control) were enhanced compared with prosaccades in the VA/VL but not in the MD, which is surprising given MD's connection to executive regions. Copyright © 2010 The American Physiological Society
Auditory Nerve Fibers Excite Targets Through Synapses That Vary in Convergence, Strength, and Short-Term PlasticityCao, Xiao-Jie; Oertel, Donata
doi: 10.1152/jn.00451.2010pmid: 20739600
Abstract Auditory nerve fibers are the major source of excitation to the three groups of principal cells of the ventral cochlear nucleus (VCN), bushy, T stellate, and octopus cells. Shock-evoked excitatory postsynaptic currents (eEPSCs) in slices from mice showed systematic differences between groups of principal cells, indicating that target cells contribute to determining pre- and postsynaptic properties of synapses from spiral ganglion cells. Bushy cells likely to be small spherical bushy cells receive no more than three, most often two, excitatory inputs; those likely to be globular bushy cells receive at least four, most likely five, inputs. T stellate cells receive 6.5 inputs. Octopus cells receive >60 inputs. The N -methyl- d -aspartate (NMDA) components of eEPSCs were largest in T stellate, smaller in bushy, and smallest in octopus cells, and they were larger in neurons from younger than older mice. The average AMPA conductance of a unitary input is 22 ± 15 nS in both groups of bushy cells, <1.5 nS in octopus cells, and 4.6 ± 3 nS in T stellate cells. Sensitivity to philanthotoxin (PhTX) and rectification in the intracellular presence of spermine indicate that AMPA receptors that mediate eEPSCs in T stellate cells contain more GluR2 subunits than those in bushy and octopus cells. The AMPA components of eEPSCs were briefer in bushy (0.5 ms half-width) than in T stellate and octopus cells (0.8–0.9 ms half-width). Widening of eEPSCs in the presence of cyclothiazide (CTZ) indicates that desensitization shortens eEPSCs. CTZ-insensitive synaptic depression of the AMPA components was greater in bushy and octopus than in T stellate cells. Copyright © 2010 The American Physiological Society
Loss of Leptin Receptors on Hypothalamic POMC Neurons Alters Synaptic InhibitionChun, Sung Kun; Jo, Young-Hawn
doi: 10.1152/jn.00371.2010pmid: 20844117
Abstract Adaptive changes in hypothalamic neural circuitry occur in response to alterations in nutritional status. This plasticity at hypothalamic synapses contributes to the control of food intake and body weight. Here we show that genetic ablation of leptin receptor gene expression in pro-opiomelanocortin (POMC) neurons (POMC: Lepr −/− GFP) induces alterations at synapses on POMC neurons in the arcuate nucleus of the hypothalamus. Our studies reveal that POMC: Lepr −/− GFP mice have decreased frequency of spontaneous GABAergic, but not glutamatergic, postsynaptic currents at synapses on POMC neurons. The decay time course of GABAergic spontaneous inhibitory postsynaptic currents (sIPSCs) onto POMC neurons in POMC: Lepr −/− GFP mice is significantly slower than that of sIPSCs in control animals. While analysis of individual miniature IPSCs shows lowered baseline activity, this tonic decrease is associated with an increased amplitude and slow decay of mini-IPSCs onto POMC neurons in POMC: Lepr −/− GFP mice. Moreover, POMC neurons receive greater total ionic flux per GABAergic event in the absence of leptin receptor signaling. In addition, treatment with the alpha 3 subunit-containing GABA A receptor modulator SB-205384 enhances GABAergic transmission only onto POMC neurons in POMC: Lepr −/− GFP mice. Single-cell RT-PCR analysis further supports the expression of the alpha 3 subunit of the GABA A receptor on POMC neurons in POMC: Lepr −/− GFP mice. Finally, the responses to the GABA A receptor agonist isoguvacine of POMC neurons are significantly smaller in POMC: Lepr −/− GFP than in control animals. Therefore our present work demonstrates that loss of leptin signaling in POMC neurons induces synaptic alterations at POMC synapses that may play an essential role in energy homeostasis. Copyright © 2010 The American Physiological Society
Hypertension Induced by Angiotensin II and a High Salt Diet Involves Reduced SK Current and Increased Excitability of RVLM Projecting PVN NeuronsChen, Qing-Hui; Andrade, Mary Ann; Calderon, Alfredo S.; Toney, Glenn M.
doi: 10.1152/jn.01013.2009pmid: 20719931
Abstract Although evidence indicates that activation of presympathetic paraventricular nucleus (PVN) neurons contributes to the pathogenesis of salt-sensitive hypertension, the underlying cellular mechanisms are not fully understood. Recent evidence indicates that small conductance Ca 2+ -activated K + (SK) channels play a significant role in regulating the excitability of a key group of sympathetic regulatory PVN neurons, those with axonal projections to the rostral ventrolateral medulla (RVLM; i.e., PVN-RVLM neurons). In the present study, rats consuming a high salt (2% NaCl) diet were made hypertensive by systemic infusion of angiotensin II (AngII), and whole cell patch-clamp recordings were made in brain slice from retrogradely labeled PVN-RVLM neurons. To determine if the amplitude of SK current was altered in neurons from hypertensive rats, voltage-clamp recordings were performed to isolate SK current. Results indicate that SK current amplitude ( P < 0.05) and density ( P < 0.01) were significantly smaller in the hypertensive group. To investigate the impact of this on intrinsic excitability, current-clamp recordings were performed in separate groups of PVN-RVLM neurons. Results indicate that the frequency of spikes evoked by current injection was significantly higher in the hypertensive group ( P < 0.05–0.01). Whereas bath application of the SK channel blocker apamin significantly increased discharge of neurons from normotensive rats ( P < 0.05–0.01), no effect was observed in the hypertensive group. In response to ramp current injections, subthreshold depolarizing input resistance was greater in the hypertensive group compared with the normotensive group ( P < 0.05). Blockade of SK channels increased depolarizing input resistance in normotensive controls ( P < 0.05) but had no effect in the hypertensive group. On termination of current pulses, a medium afterhyperpolarization potential (mAHP) was observed in most neurons of the normotensive group. In the hypertensive group, the mAHP was either small or absent. In the latter case, an afterdepolarization potential (ADP) was observed that was unaffected by apamin. Apamin treatment in the normotensive group blocked the mAHP and revealed an ADP resembling that seen in the hypertensive group. We conclude that diminished SK current likely underlies the absence of mAHPs in PVN-RVLM neurons from hypertensive rats. Both the ADP and greater depolarizing input resistance likely contribute to increased excitability of PVN-RVLM neurons from rats with AngII-Salt hypertension. Copyright © 2010 The American Physiological Society
Evoked Potentials in Motor Cortical Local Field Potentials Reflect Task Timing and Behavioral PerformanceKilavik, Bjørg Elisabeth; Confais, Joachim; Ponce-Alvarez, Adrián; Diesmann, Markus; Riehle, Alexa
doi: 10.1152/jn.00250.2010pmid: 20884766
Abstract Evoked potentials (EPs) are observed in motor cortical local field potentials (LFPs) during movement execution (movement-related potentials MRPs) and in response to relevant visual cues (visual evoked potentials VEPs). Motor cortical EPs may be directionally selective, but little is known concerning their relation to other aspects of motor behavior, such as task timing and performance. We recorded LFPs in motor cortex of two monkeys during performance of a precued arm-reaching task. A time cue at the start of each trial signaled delay duration and thereby the pace of the task and the available time for movement preparation. VEPs and MRPs were strongly modulated by the delay duration, VEPs being systematically larger in short-delay trials and MRPs larger in long-delay trials. Despite these systematic modulations related to the task timing, directional selectivity was similar in short and long trials. The behavioral reaction time was positively correlated with MRP size and negatively correlated with VEP size, within sessions. In addition, the behavioral performance improved across sessions, in parallel with a slow decrease in the size of VEPs and MRPs. Our results clearly show the strong influence of the behavioral context and performance on motor cortical population activity during movement preparation and execution. Copyright © 2010 The American Physiological Society
Activity-Dependent Regulation of the Binomial Parameters p and n at the Mouse Neuromuscular Junction In VivoWang, Xueyong; Wang, Qingbo; Engisch, Kathrin L.; Rich, Mark M.
doi: 10.1152/jn.00460.2010pmid: 20739593
Abstract Block of neurotransmission at the mammalian neuromuscular junction triggers an increase in the number of vesicles released (quantal content). The increase occurs whether nerve and muscle activity are both blocked by placement of a tetrodotoxin (TTX) containing cuff on the nerve or whether muscle activity is selectively blocked by injection of α-bungarotoxin (BTX). We used ANOVA to examine whether the mechanism underlying the increase in quantal content differed between the two types of activity blockade. We found that TTX-induced blockade increased the probability of release ( p ), whereas BTX-induced blockade increased the number of releasable vesicles ( n ). The lack of increase in p when postsynaptic activity was blocked with BTX suggests that block of presynaptic activity triggers the increase. To determine whether n is regulated by mismatch of pre- and postsynaptic activity introduced by BTX injection we combined BTX and TTX and still found an increase in n . We conclude that block of acetylcholine binding to acetylcholine receptors during spontaneous release triggers the increase in n . Copyright © 2010 The American Physiological Society
Decision-Making, Errors, and Confidence in the BrainRolls, Edmund T.; Grabenhorst, Fabian; Deco, Gustavo
doi: 10.1152/jn.00571.2010pmid: 20810685
Abstract To provide a fundamental basis for understanding decision-making and decision confidence, we analyze a neuronal spiking attractor-based model of decision-making. The model predicts probabilistic decision-making with larger neuronal responses and larger functional magnetic resonance imaging (fMRI) blood-oxygen-level-dependent (BOLD) responses on correct than on error trials because the spiking noise-influenced decision attractor state of the network is consistent with the external evidence. Moreover, the model predicts that the neuronal activity and the BOLD response will become larger on correct trials as the discriminability Δ I increases and confidence increases and will become smaller as confidence decreases on error trials as Δ I increases. Confidence is thus an emergent property of the model. In an fMRI study of an olfactory decision-making task, we confirm these predictions for cortical areas including medial prefrontal cortex and the cingulate cortex implicated in choice decision-making, showing a linear increase in the BOLD signal with Δ I on correct trials, and a linear decrease on error trials. These effects were not found in a control area, the orbitofrontal cortex, where reward value useful for the choice is represented on a continuous scale but that is not implicated in the choice itself. This provides a unifying approach to decision-making and decision confidence and to how spiking-related noise affects choice, confidence, synaptic and neuronal activity, and fMRI signals. Footnotes Copyright © 2010 The American Physiological Society
Sensory-Spatial Transformations in the Left Posterior Parietal Cortex May Contribute to Reach TimingTorres, Elizabeth B.; Raymer, Anastasia; Gonzalez Rothi, Leslie J.; Heilman, Kenneth M.; Poizner, Howard
doi: 10.1152/jn.00089.2010pmid: 20810686
Abstract The posterior parietal cortex (PPC) contains viewer-centered spatial maps important for reaching movements. It is known that spatial reaching deficits emerge when this region is damaged, yet less is known about temporal deficits that may also emerge because of a failure in sensory-spatial transformations. This work introduces a new geometric measure to quantify multimodal sensory transformation and integration deficits affecting the tempo of reaching trajectories that are induced by injury to the left PPC. Erratic rates of positional change involving faulty maps from rotational angular displacements to translational linear displacements contributed to temporal abnormalities in the reach. Such disruptions were quantified with a time-invariant geometric measure. This measure, paired with an experimental paradigm that manipulated the source of visual guidance for reaches, was used to compare the performance of normal controls to those from a patient (T.R.) who had a lesion in his left-PPC. For controls, the source of visual guidance significantly scaled the tempo of target-directed reaches but did not change the geometric measure. This was not the case in patient T.R., who altered this measure. With continuous, extrapersonal visual feedback of the target, however, these abnormalities improved. Vision of the target rather than vision of his moving hand also improved his arm-joint rotations for posture control. These results show that the left PPC is critically important for visuo-motor transformations that specifically rely on extrapersonal cues to align rotational-arm and linear-hand displacements and to continuously integrate their rates of change. The intactness of this system contributes to the fluidity of the reach's tempo. Copyright © 2010 The American Physiological Society
Cortical Organization in the Etruscan Shrew (Suncus etruscus)Roth-Alpermann, Claudia; Anjum, Farzana; Naumann, Robert; Brecht, Michael
doi: 10.1152/jn.00762.2009pmid: 20668271
Abstract Cortical organization in the Etruscan shrew is of comparative interest because of its small size and because the Etruscan shrew is an amazing tactile hunter. Here we investigated cortical organization in Etruscan shrews by electrophysiological mapping. We developed an anesthesia protocol for this very small mammal in which we combined massive application of local anesthesia, very slow induction of general anesthesia, and passive cooling. Under this anesthesia regime, we characterized auditory, visual, and somatosensory cortical responses. We found that large parts of shrew cortex respond to such stimuli. Of the responsive sites, a small fraction (∼14%) responded to visual stimuli in a caudally located region. Another small fraction of sites (∼11%) responded to auditory stimuli in a centrally located region. The majority of sites (∼75%) responded to tactile stimuli. We identified two topographically organized somatosensory areas with small receptive fields referred to as putative primary somatosensory cortex and putative secondary somatosensory cortex. In a posterior-lateral region that partially overlaps with piriform cortex, we observed large somatosensory receptive fields and often polysensory responses. In an anterior-lateral region that partially overlaps with piriform cortex, we observed large unimodal somatosensory receptive fields. Our findings demonstrate a remarkable degree of tactile specialization in Etruscan shrew cortex. Copyright © 2010 The American Physiological Society
Spectral Responses in Zebrafish Horizontal Cells Include a Tetraphasic Response and a Novel UV-Dominated Triphasic ResponseConnaughton, Victoria P.; Nelson, Ralph
doi: 10.1152/jn.00644.2009pmid: 20610786
Abstract Zebrafish are tetrachromats with red (R, 570 nm), green (G, 480 nm), blue (B, 415 nm), and UV (U, 362 nm) cones. Although neurons in other cyprinid retinas are rich in color processing neural circuitry, spectral responses of individual neurons in zebrafish retina, a genetic model for vertebrate color vision, are yet to be studied. Using dye-filled sharp microelectrodes, horizontal cell voltage responses to light stimuli of different wavelengths and irradiances were recorded in a superfused eyecup. Spectral properties were assessed both qualitatively and quantitatively. Six spectral classes of horizontal cell were distinguished. Two monophasic response types (L1 and L2) hyperpolarized at all wavelengths. L1 sensitivities peaked at 493 nm, near the G cone absorbance maximum. Modeled spectra suggest equally weighted inputs from both R and G cones and, in addition, a “hidden opponency” from blue cones. These were classified as R−/G−/(b+). L2 sensitivities were maximal at 563 nm near the R cone absorbance peak; modeled spectra were dominated by R cones, with lesser G cone contributions. B and UV cone signals were small or absent. These are R−/g−. Four chromatic (C-type) horizontal cells were either depolarized (+) or hyperpolarized (−) depending on stimulus wavelength. These types are biphasic (R+/G−/B−) with peak excitation at 467 nm, between G and B cone absorbance peaks, UV triphasic (r−/G+/U−) with peak excitation at 362 nm similar to UV cones, and blue triphasic (r−/G+/B−/u−) and blue tetraphasic (r−/G+/B−/u+), with peak excitation at 409 and 411 nm, respectively, similar to B cones. UV triphasic and blue tetraphasic horizontal cell spectral responses are unique and were not anticipated in previous models of distal color circuitry in cyprinids. Copyright © 2010 The American Physiological Society