bluuebunny/crossref_metadata_2025 huggingface dataset:
Cannabinoid agonists inhibit the activation of 5-HT3 receptors in rat nodose ganglion neurons
Authors: Fan P.
Published: December 2017

1. Effects of cannabinoid agonists on the serotonin (5-HT)3 receptor-mediated current were investigated in rat nodose ganglion neurons. Anandamide, Win 55212-2, and CP55940 inhibited the 5-HT-induced current in a concentration dependent manner. IC50 values were 190, 310, and 94 nM for anandamide, Win 55212-2, and CP55940, respectively, and 1.6 microM for the nonpsychoactive enantiomer CP56667. This inhibition was slowly developing, noncompetitive, not dependent on membrane potential, and not affected by adenosine 3',5'-cyclic monophosphate (cAMP) analogues, guanosine-5'-O-(2-thiodiphosphate) (GDP-beta-S), and opioid receptor antagonist naltrexone. These data suggest that 5-HT3 receptor ion-channel is a site acted upon by cannabinoid agonists in the nervous system, and the action of cannabinoid agonists on 5-HT3 receptors may be a possible mechanism for some of the behavioral effects of cannabinoids, such as antiemesis and analgesia.
Organizing principles for voluntary movement: extending single-joint rules
Authors: Almeida G. L. , Hong D. A. , Corcos D. , Gottlieb G. L.
Published: December 2017

1. Four subjects performed fast flexions of the elbow or shoulder over three different distances. Elbow flexions were performed both in a horizontal, single-degree-of-freedom manipulandum and in a sagittal plane with the limb unconstrained. Shoulder flexions were only performed in the sagittal plane by the unconstrained limb. We simultaneously recorded kinematic and electromyographic (EMG) patterns at the “focal” joint, that which the subject intentionally flexed, and at the other, “nonfocal” joint that the subject had been instructed to not flex. 2. Comparisons of the elbow EMG patterns across tasks show that agonist and antagonist muscles were similar in pattern but not size, reflecting the net muscle torque patterns. Comparisons at the shoulder also revealed similar EMG patterns across tasks that reflected net muscle torques. 3. Comparisons of EMG patterns across joints show that elbow and shoulder flexors behaved similarly. This was not true of the extensors. The triceps EMG burst was delayed for longer distances but the posterior deltoid had an early, distance-invariant onset. 4. Similarities in EMG reflect torque demands required at the focal joint to produce flexion and at the nonfocal joint to reduce extension induced by dynamic interactions with the focal, flexing joint. These similarities appear despite very different kinematic intentions and outcomes. This argues against a strong role for length-sensitive reflexes in their generation. 5. These results support the hypothesis that movements are controlled by muscle activation patterns that are planned for the expected torque requirements of the task. This general rule is true whether we are performing single-joint or multiple-joint movements, with or without external constraints. The similarities between single-joint and multijoint movement control may be a consequence of ontogenetic development of multijoint movement strategies that prove useful and are therefore also expressed under the constrained conditions of specialized tasks such as those performed in single-joint manipulanda.
Mechanisms underlying direction selectivity of neurons in the primary visual cortex of the macaque
Authors: Sato H. , Katsuyama N. , Tamura H. , Hata Y. , Tsumoto T.
Published: December 2017

1. We studied the effects of blocking intracortical inhibition by microiontophoretic administration of bicuculline methiodide (BMI), a selective antagonist for gamma-aminobutyric acid-A receptors, on direction sensitivity of 103 neurons in the primary visual cortex (VI) of anesthetized and paralyzed monkeys. 2. The direction selectivity index (DSI) of each cell was calculated for the control response and response during the BMI administration at the optimal stimulus orientation to assess the directionality of an individual cell. 3. The averaged direction tuning of visual responses of cells was sharp in layers IVa and IVb, moderate in both interblob and blob regions of layer II/III and layers V and VI, and poor in layers IVc alpha and IVc beta. 4. Iontophoretic administration of BMI uncovered or facilitated responses to stimuli moving in the nonpreferred direction, and reduced DSIs of cells to a varying extent in all the layers except layer VI. Responses to stimuli moving in the preferred direction were also facilitated so that a slight bias of response toward the originally preferred direction remained during BMI administration in most cells. 5. Most of the cells in layers II/III (both blobs and interblobs) and IVb that receive inputs from layers IVc alpha and IVc beta showed a clear reduction of direction selectivity during BMI administration. This result suggests that intracortical inhibition plays an important role in the elaboration of direction selectivity at the second stage of information processing in VI. 6. The direction selectivity of cells in layer VI was most resistant to the effects of BMI, suggesting that it is dependent on excitatory inputs that are already direction selective, even though the sample size of this layer was small. 7. In direction-selective cells outside layer VI, responses to a stimulus moving in the preferred direction were enhanced in a way that was linearly related with those in the nonpreferred direction as the BMI dose was increased. This suggests that various amounts of inhibition interact linearly with directionally biased excitatory inputs to raise the firing threshold to various levels so as to produce various degrees of directionality. 8. These results suggest that, in most of the directionally sensitive cells except for those in layer VI, there are excitatory inputs which are bidirectional but slightly biased to one direction, and that the intracortical inhibition raises a threshold level of responses to excitatory inputs so that the response become direction selective.
Electrophysiological responses of single olfactory bulb neurons to binary mixtures of amino acids in the channel catfish, Ictalurus punctatus
Authors: Kang J. , Caprio J.
Published: December 2017

1. For the first time in any vertebrate, responses of single olfactory bulb neurons to odorant mixtures were studied quantitatively in the channel catfish, Ictalurus punctatus. 2. Extracellular electrophysiological responses of 61 single olfactory bulb neurons from 36 channel catfish to binary mixtures of amino acids and to their components were recorded simultaneously with the electro-olfactogram (EOG). Tested were a total of 297 mixture trials consisting of 18 different stimulus pairs formed from 8 amino acids. 3. For 42% (126 of the 297) of the tests, no significant change (N) from spontaneous activity occurred. Responses to the remaining 171 tests of binary mixtures were excitatory (E; 29%) or suppressive (S; 29%). No response type was associated with any specific mixture across the neurons sampled. 4. Mixture interactions that changed response types (E or S) from those observed to the individual components were rare, because 89% of the responses of single olfactory bulb neurons to the tested binary mixtures were classified similarly as the responses to at least one of the components. 5. Responses of single olfactory bulb neurons were generally predictable for binary mixtures whose component responses were classified as both E, both S, and both N. For binary mixtures whose component responses were classified differently (e.g., one component evoked excitatory responses and the other evoked suppressive responses), the predictability of the response was dependent on the specific mixture type.
Cutaneous responsiveness of lumbar spinal neurons in awake and halothane-anesthetized sheep
Authors: Herrero J. F. , Headley P. M.
Published: December 2017

1. To compare the responsiveness of lumbar spinal neurons to peripheral sensory stimuli under normal physiological conditions and under halothane anesthesia, we performed a study in sheep that were prepared chronically. This permitted recordings to be made in the same animals either when they were awake and free from recent surgery, drugs, and training and only partially restrained or when they were anesthetized with halothane. 2. We recorded 261 units in dorsal and ventral horns under conscious conditions. Of these, 19% had no detectable receptive field (RF) and 44% had responses dominated by proprioceptive inputs; these units were not investigated in detail. The remaining 96 neurons (37%) had clearly defined cutaneous RFs. Of these, most (72%) had wide-dynamic-range (WDR; convergent, multireceptive) properties, 19% were low-threshold mechanoreceptive (LTMR), and 9% were high-threshold mechanoreceptive (HTMR). These units with cutaneous RFs were investigated in greater detail. 3. The spontaneous activity under these awake conditions was low (< 4 spikes/s) for nearly all units in all three categories. The mechanical threshold of the most sensitive (central) part of the cutaneous RF was assessed with von Frey bristles. Thresholds were < 5 mN for all LTMR neurons, < 1-30 mN for WDR neurons, and > 80 mN for HTMR neurons. The size of the low-threshold cutaneous RFs was significantly larger for WDR neurons (mean 46 cm2) and HTMR neurons (45 cm2) than for LTMR neurons (24 cm2). The RFs were distributed all over the ipsilateral hindlimb. Large RFs were mostly proximal, whereas small RFs were distributed relatively evenly over the limb. 4. Recordings were made from a further 165 units while the animals were under halothane anesthesia. With 86 neurons having cutaneous peripheral RFs, the proportions having LTMR, HTMR, or WDR characteristics were very similar to those in awake animals. Under halothane the ongoing activity of WDR units was slightly (but significantly) less. The threshold to von Frey bristle stimulation was significantly higher only for WDR units, in both dorsal and ventral horns. The mean size of cutaneous RFs was significantly larger in all classes of units recorded under halothane anesthesia. For WDR units this was true for cells in both dorsal and ventral horns. This effect on mean values was due to a larger proportion of units with very large fields under anesthesia, particularly in the dorsal horn. 5. Comparison of the data from conscious animals with published results of acute experiments indicates that acute recording conditions do not distort the relative distribution and resting characteristics of these three functional categories of lumbar spinal neurons as much as might have been expected. 6. Halothane does not have major effects on the resting sensory responsiveness of spinal neurons with cutaneous RFs. The increase in RF area, which contrasts with most results from acute studies, is likely to be due to a dampening of descending inhibitory control mechanisms.
Muscarine inhibits omega-conotoxin-sensitive calcium channels in a voltage- and time-dependent mode in the human neuroblastoma cell line SH-SY5Y
Authors: Toselli M. , Perin P. , Taglietti V.
Published: December 2017

1. Calcium channel modulation by muscarine was investigated in cultured human neuroblastoma SH-SY5Y cells using the whole cell variant of the patch-clamp technique. 2. In SH-SY5Y cells, omega-conotoxin (omega-CgTx)-sensitive, high-voltage-activated Ca2+ current density gradually increased from approximately 1 microA/cm2 in undifferentiated cells to 4 microA/cm2 after approximately 20 days of application of the differentiating agent retinoic acid. 3. In differentiated SH-SY5Y cells, muscarine reversibly decreased high-voltage-activated omega-CgTx-sensitive Ba2+ currents in a concentration-dependent way. Maximum inhibition (approximately 65%) measured at 0 mV was obtained with 30 microM muscarine and the IC50 was 1 microM. 4. Current inhibition obtained with 30 microM muscarine was suppressed by the specific M2 and M3 antagonists AFDX-116 and 4-diphenylacetoxy-N-methyl-piperidine methiodide (0.3 microM; 87% suppression), but not by the M1 antagonist pirenzepine. 5. Muscarine-induced current suppression was prevented by pretreatment of the cells with pertussis toxin and mimicked by intracellular application of guanosine 5'-[gamma-thio]triphosphate. 6. In several cells, muscarinic inhibition was characterized by a clear slowdown of Ba2+ current activation at low test potentials. Both inhibition and slowdown of activation were attenuated at more positive potentials and could be partially relieved by strong conditioning depolarizations. 7. These results indicate that muscarinic inhibition of omega-CgTx-sensitive Ca2+ channel current occurs through activation of specific muscarinic receptors and the modulatory mechanism operates through activation of a guanosine 5'-triphosphate-binding protein sensitive to pertussis toxin. Our results suggest that a blocking molecule interacts in a voltage-dependent manner with the Ca2+ channel without involvement of intracellular Ca2+ mobilization or activation of protein kinase C or cyclic nucleotide protein kinases. A simple model describing the reactions involved is proposed.
Addition of carbonic anhydrase augments extracellular pH buffering in rat cerebral cortex
Authors: Huang W. , Smith S. E. , Chesler M.
Published: December 2017

1. The ability of the extracellular space to buffer rapid alkaline shifts was studied in rat cortex in vitro and in vivo. Alkaline shifts were generated by iontophoresis of OH- or were evoked by pressure ejection of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA). 2. In cortical slices, alkaline shifts induced by OH- were enhanced by the carbonic anhydrase (CA) inhibitor benzolamide (83 +/- 16%, mean +/- SE), and were decreased by superfusion of 10 mg/l CA (-59 +/- 4%). CA had no effect at 1 mg/l, and no additional effect at 100 mg/l. 3. In slices, and in vivo, alkaline shifts induced by AMPA were similarly enhanced by benzolamide and decreased by superfusion of CA. 4. These data indicate that extracellular CA activity is less than that required for maximum buffering. This suggests that equilibrium between CO2 and bicarbonate may not be attained during rapid extracellular pH shifts.
Inhibitory control of excitable dendrites in neocortex
Authors: Kim H. G. , Beierlein M. , Connors B. W.
Published: December 2017

1. Many dendrites of pyramidal cells in mature neocortex express active Na+ and Ca2+ conductances. Dendrites are also the target of numerous inhibitory synapses. We examined the interactions between the intrinsic excitability of dendrites and synaptic inhibition using whole cell recordings from the apical dendrites of layer 5 pyramidal cells. Experiments were performed on slices of somatosensory cortex from mature rats. Slices were bathed in the glutamate receptor antagonists 2-amino-5-phosphonopentanoic acid and 6,7-dinitroquinoxaline-2,3-dione, and maintained at 32-36 degrees C. 2. In agreement with previous findings, intradendritic current injection evoked two distinct types of dendritic firing. Type I dendrites generated monophasic fast spikes, whereas type II dendrites showed more complex firing patterns, consisting of fast and slow spike components. 3. Stimulation of cortical layers 2/3 evoked fast inhibitory postsynaptic potentials (IPSPs) in all dendrites tested. IPSP reversal potentials were bimodally distributed, with means of about -53 and -85 mV when recorded with high-Cl(-)-concentration-filled electrodes. Interestingly, IPSP reversal potentials were correlated with the type of dendritic spiking pattern. 4. IPSPs were able to delay, completely block, or partially block spiking in dendrites, depending on the relative timing between inhibition and dendritic spiking. Slow, Ca(2+)-dependent spike components could be blocked selectively by IPSPs. Furthermore, inhibition could either phase advance or phase delay repetitive patterns of dendritic spiking, depending on the timing of the IPSP.
Neuronal elements that mediate escape swimming and suppress feeding behavior in the predatory sea slug Pleurobranchaea
Authors: Jing J. , Gillette R.
Published: December 2017

1. The white, bilaterally paired A1 interneurons of the cerebropleural ganglion of Pleurobranchaea californica fire rhythmic bursts of action potentials during escape swimming behavior. We studied the role of the A1s in swimming behavior and pattern generation in whole animal and isolated CNS preparations. 2. The escape swim is a cyclic sequence of dorsal and ventral flexions of the body. During the swim, A1 bursts precede and accompany the dorsal flexion phase of the cycle. Hyperpolarization of A1 to prevent spike activity interrupts swimming behavior in the whole animal and fictive swimming in the isolated CNS. Stimulated A1 activity was not observed to cause swimming in whole animals, and was only occasionally sufficient to trigger fictive swimming activity in the isolated CNS. 3. In quiescent whole animal preparations, stimulation of a single A1 normally causes a single dorsal flexion followed by body flexion to the side contralateral to the stimulated cell; characteristically, A1 spike activity stimulates feedback inhibition coinciding with the end of dorsal flexion and the onset of contralateral flexion. 4. A1 spike activity suppresses feeding behavior and causes proboscis retraction in whole animal preparations induced to feed. A1 activity also suppresses fictive feeding driven by stimulation of the critical phasic paracerebral neurons (PCps) of the motor network of feeding in the isolated CNS. Concomitantly, A1 spikes cause potent inhibition of the PCp interneurons. 5. The A1s are specifically excited by noxious mechanical and chemical stimuli, but are not affected by feeding stimuli or the occurrence of feeding behavior. 6. We conclude that the A1 neurons are elements of an escape swimming pattern generator, and that they are probably homologous to the similar C2 neurons of the nudibranch Tritonia diomedea. One of their functions outside of generating the swim pattern may be the suppression of feeding behavior in response to noxious stimulation. These observations provide a neural mechanism for the original observations of the dominance of escape swimming behavior over feeding.
Calcium-dependent plateau potentials in a crab stomatogastric ganglion motor neuron. I. Calcium current and its modulation by serotonin
Authors: Zhang B. , Harris-Warrick R. M.
Published: December 2017

1. Using current- and voltage-clamp techniques, we examined the biophysical properties of a voltage-dependent Ca2+ current and its physiological role in plateau potential generation in the dorsal gastric (DG) motor neuron of the stomatogastric ganglion in the crab, Cancer borealis. 2. Stimulation of one of a set of identified serotonergic/cholinergic mechanosensory cells, the gastropyloric receptor (GPR) cells, induced plateau potentials in DG. A brief pressure application of serotonin (5-HT) closely mimicked the effect of the GPR cells. The 5-HT-evoked plateau in DG was not blocked by the sodium channel blocker, tetrodotoxin (TTX), or a combination of TTX with potassium channel blockers, including tetraethylammonium (TEA) and 4-aminopyridine (4-AP), and the Ih blocker, CsCl. The 5-HT-evoked plateau was eliminated by the Ca2+ channel blockers Co2+ and Cd2+, suggesting that Ca2+ entry is essential for plateau potentials in DG. During the plateau, we observed a 30% decrease in input resistance. 3. When sodium and potassium currents were blocked pharmacologically, injection of suprathreshold depolarizing current evoked all-or-none plateau-like responses lasting several seconds, even in the absence of 5-HT. This response was blocked by Ca2+ channel blockers, further supporting a role for Ca2+ in plateau generation. 5-HT significantly prolonged the duration of this plateau. 4. We isolated a voltage-dependent Ca2+ current in voltage-clamped DG neurons. This current was analyzed with the use of either Ca2+ or Ba2+ as the charge carrier after other currents had been maximally blocked with extracellular TTX, TEA, 4-AP, and CsCl and intracellular loading with Cs+ and ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA). The Ca2+ current was detectable at -45 mV, peaked at -15 mV, and was estimated to reverse at +45 mV. Co2+ and Cd2+ effectively blocked the Ca2+ current. 5. The voltage dependence of activation of the Ca2+ current was quantantitively analyzed by fitting the voltage-conductance relation with a third power Boltzmann relation. The maximum conductance (gA), half-activation voltage (VA) for individual gating steps, and the slope steepness (k) were 0.19 +/- 0.02 (SE) microS, -36.5 +/- 2.0 mV, and 4.4 +/- 1.4 mV/e-fold, respectively. 6. 5-HT significantly potentiated the gA by approximately 42% without affecting VA and k. 7. We conclude from our current- and voltage-clamp results that a voltage-dependent Ca2+ current plays an important role in generating plateau potentials in the DG neuron. Enhancement of the voltage-dependent Ca2+ current by 5-HT is one of the mechanisms for 5-HT-evoked plateau potentials.
Relationship between synaptic activity and prolonged field bursts in the dentate gyrus of the rat hippocampal slice
Authors: Schweitzer J. S. , Williamson A.
Published: December 2017

1. Previous studies in the dentate granule cell layer of the rat hippocampal slice have demonstrated that nonsynaptic, seizurelike prolonged field bursts occur in conditions of low extracellular Ca2+ concentration ([Ca2+]o) and elevated [K+]o. We hypothesize that the extracellular ion concentration changes induced by synaptic activation of dentate granule cells would be sufficient to initiate these nonsynaptic bursts. 2. Using ion-selective electrode recording, we observed large changes in [Ca2+]o (from 1.3 mM baseline to approximately 0.7 mM) and [K+]o (from 3.5 to approximately 12 mM) in the dentate granule cell layer during repetitive electrical stimulation of the perforant path in rat hippocampal slices. Concomitant with these changes, bursts of population spikes similar to those seen during spontaneous prolonged field bursts appeared between the individual stimulus-evoked responses in the dentate gyrus in many of the slices studied (19 of 27). 3. Blockade of N-methyl-D-aspartate (NMDA), non-NMDA, and gamma-aminobutyric acid-A (GABAA)-mediated synaptic transmission during perforant path stimulation resulted in a marked reduction of the ion concentration changes and a loss of both stimulus-evoked and stimulus-independent population spikes in the dentate gyrus. 4. When slices were perfused with solutions containing [Ca2+]o and [K+]o equivalent to those measured during perforant path stimulation (i.e., 0.7 and 12 mM, respectively), spontaneous prolonged field bursts appeared in the dentate gyrus. Addition of NMDA, non-NMDA, and GABAA receptor antagonists did not prevent the occurrence of these spontaneous bursts. 5. We conclude that changes in [Ca2+]o and [K+]o sufficient to produce prolonged field bursts may be created in the dentate granule cell layer by perforant path stimulation. These effects are dependent on synaptic transmission. Once these ionic conditions occur, they are sufficient to trigger prolonged field bursts independent of fast amino-acid-mediated synaptic transmission. A similar mechanism could be important during the interictal-ictal transition in vivo.
Organization of striate cortex of alert, trained monkeys (Macaca fascicularis): ongoing activity, stimulus selectivity, and widths of receptive field activating regions
Authors: Snodderly D. M. , Gur M.
Published: December 2017

1. In alert macaque monkeys, multiunit activity is encountered in an alternating sequence of silent and spontaneously active zones as an electrode is lowered through the striate cortex (V1). 2. Individual neurons that are spontaneously active in the dark usually have a maintained discharge in the light. Because both types of discharge occur in the absence of deliberate stimulation, we call them the "ongoing" activity. The zones with ongoing activity correspond to the cytochrome oxidase (CytOx)-rich geniculorecipient layers 4A, 4C, and 6, whereas the adjacent layers 2/3, 4B, and 5 have little ongoing activity. 3. The widths of receptive field activating regions (ARs) are positively correlated with the cells' ongoing activity. Cells with larger ARs are preferentially located in the CytOx-rich (input) layers, and many are unselective for stimulus orientation. However, approximately 90% of the cells in the silent layers are orientation selective, and they often have small ARs. 4. The laminar distribution of selectivity for orientation and direction of movement in alert animals is consistent with earlier results from anesthetized animals, but the laminar distribution of AR widths differs. In alert macaques, the ARs of direction-selective cells in layer 4B and of orientation-selective cells in layer 5 are among the smallest in V1. 5. Our findings indicate that the input layers of V1 (4A, 4C, and 6) have a diversity of AR widths, including large ones. Cortical processing produces receptive fields in some of the output layers (4B and 5) that are restricted to small ARs with high resolution of spatial position. These results imply potent lateral and/or interlaminar interactions in alert animals in early cortical processing. The diversity of AR widths generated in V1 may contribute to detection of fine detail in the presence of contrasting backgrounds--the early stages of figure-ground discrimination.
Trajectory adaptation to a nonlinear visuomotor transformation: evidence of motion planning in visually perceived space
Authors: Flanagan J. R. , Rao A. K.
Published: December 2017

1. Although reaching movements are characterized by hand paths that tend to follow roughly straight lines in Cartesian space, a fundamental issue is whether this reflects constraints associated with perception or movement production. 2. To address this issue, we examined two-joint planar reaching movements in which we manipulated the mapping between actual and visually perceived motion. In particular, we used a nonlinear transformation such that straight line hand paths in Cartesian space would result in curved paths in perceived space and vice versa. 3. Under these conditions, subjects learned to make straight line paths in perceived space even though the paths of the hand in Cartesian space were markedly curved. In contrast, when the motion was perceived in Cartesian space (i.e., in the absence of a nonlinear distortion), straight line hand paths were observed. 4. These findings suggest that visually guided reaching movements are planned in a perceptual frame of reference. Reaching movements in the horizontal plane are adapted so as to produce straight lines in visually perceived space.
Extraretinal modulation of cerebral blood flow in the human visual cortex: implications for saccadic suppression
Authors: Paus T. , Marrett S. , Worsley K. J. , Evans A. C.
Published: December 2017

1. Extraretinal modulation of neuronal activity in the human brain was assessed indirectly by measuring changes in regional cerebral blood flow (rCBF) during the execution of large horizontal saccades in complete darkness. With the use of positron emission tomography, rCBF was measured in 9 volunteers as they made 40, 60, 80, 100, 110, 120, or 140 saccades during 60-s scans. 2. With increasing numbers of saccades, rCBF increased in the following oculomotor structures: the frontal eye field, the superior colliculus, and the cerebellar vermis. In parallel to these rCBF increases, rCBF decreased in the striate cortex, adjacent extrastriate cortex, and the parietal cortex. 3. The observed rCBF decreases most likely indicate a decline in the net amount of excitatory neurotransmission in the visual cortex and, as such, may represent a neural substrate of saccadic suppression.
Medial amygdala enhances synaptic transmission and synaptic plasticity in the dentate gyrus of rats in vivo
Authors: Ikegaya Y. , Abe K. , Saito H. , Nishiyama N.
Published: December 2017

1. The present experiment was designed to test whether synaptic transmission and synaptic plasticity in the dentate gyrus were modulated by the medial amygdala (MeA). Field potentials in the dentate gyrus (DG) evoked by stimulations of the medial perforant path (PP) were extracellularly recorded in anesthetized rats. 2. Although single-pulse stimulation of the MeA augmented PP stimulation-evoked population spike amplitude in the DG transiently, high-frequency stimulation (100 Hz for 1 s) of the MeA induced long-lasting enhancement of synaptic transmission that was not occluded by PP tetanus-induced long-term potentiation (LTP). 3. When high-frequency stimulation of the MeA was applied concurrently with weak tetanus of the PP, which alone induced only marginal LTP, the magnitude of LTP increased considerably. 4. These results demonstrate that neuron activities in the MeA induce short- and long-lasting changes in the excitability of the PP-DG synapses and thereby enhance their synaptic plasticity.
Mechanism of block by ZD 7288 of the hyperpolarization-activated inward rectifying current in guinea pig substantia nigra neurons in vitro
Authors: Harris N. C. , Constanti A.
Published: December 2017

1. The effects of the novel bradycardic agent 4-(N-ethyl-N-phenylamino)-1,2-dimethyl-6-(methylamino) pyrimidinium chloride (ZD 7288) (Zeneca) were investigated on the hyperpolarization-activated cationic current (Ih) in guinea pig substantia nigra pars compacta neurons in vitro, using a single-microelectrode current-clamp/voltage-clamp technique. 2. Under current-clamp conditions, injection of large negative current pulses (0.1-0.5 nA, 400 ms) evoked a slow depolarizing "sag" in the electrotonic potential due to activation of the slow inward (anomalous) rectifier. In voltage-clamp recordings, hyperpolarizing voltage steps from a holding potential of -60 mV (close to resting potential) elicited slow inward current relaxations with kinetic properties similar to those seen for other neuronal Ihs. 3. ZD 7288 (10-100 microM) produced a consistent abolition of the electrotonic potential sag with no effect on membrane potential or spike properties. Under voltage clamp, Ih amplitude was clearly reduced in a time- and concentration-dependent manner (apparent half-maximum blocking concentration = 2 microM); full block of Ih was typically achieved after 10-15 min of exposure to 50 microM ZD 7288, with no significant recovery observed after 1 h of washing. 4. A similar (although more rapid) block of Ih was seen after application of 3-5 mM Cs+ (partially reversible after 30 min of washing). 5. Partial block of Ih by 10 microM ZD 7288 was accompanied by a reduction in the maximum amplitude of the Ih activation curve, a small negative shift in its position on the voltage axis, and a linearization of the steady-state current-voltage relationship. The estimated Ih reversal potential, however, remained unaffected. 6. In 10 microM ZD 7288, the time course of Ih activation and deactivation was significantly slowed (within the range of -70 to -120 mV for the activation time constant and -70 to -90 mV for the inactivation time constant). 7. Blockade of Ih by ZD 7288 or Cs+ was independent of prior Ih activation (i.e., non-use dependent). 8. Intracellular loading with ZD 7288 also abolished the sag in the electrotonic voltage response and Ih relaxations, suggesting an intracellular site of action. By contrast, intracellular Cs+ had no effect on Ih properties. 9. Block of Ih by ZD 7288 (but not Cs+) was relieved by prolonged cell hyperpolarization, manifested as a slowly developing (half-time approximately 20 s) inward current at a holding potential of -100 mV. 10. We propose that ZD 7288, when applied externally, may behave as a "lipophilic" quaternary cation, capable of passing into the cell interior to block Ih channels in their closed state; this compound may thus prove a useful research tool, in place of Cs+, for studying the properties and significance of Ih currents in controlling neuronal function.
Outward currents in heart motor neurons of the medicinal leech
Authors: Opdyke C. A. , Calabrese R. L.
Published: December 2017

1. Outward currents were studied in isolation in heart motor neurons in the medicinal leech, using the single-electrode voltage-clamp technique. The currents were divided into four distinct types on the basis of their time and voltage characteristics and sensitivity to external Ca2+ concentration. 2. The four types were a fast transient current, IKA; a slow transient current. IK1; a noninactivating current, IK2, all measured in a bathing solution in which Co2+ was substituted for Ca2+; and a calcium-sensitive current. IK1Cal which was revealed in a bathing solution containing normal levels of Ca2+. 3. The outward currents in heart motor neurons studied in different ganglia possessed differences of quality. For example, heart motor neurons from ganglia 3 or 4 had significantly less IK2 and IK1 than neurons recorded from more posterior ganglia. Heart motor neurons from ganglion 3 often had little or no IK1. Soma input resistance, electrotonic length, and soma capacitance measured in heart motor neurons from both anterior and posterior ganglia exhibited no significant differences. 4. IKA started to activate near -45 mV with half-maximal activation at about -20 mV and was fully inactivated by 0 mV: IK1 started to activate near -45 mV with half-maximal activation at about -10 mV and was not fully inactivated by 0 mV; IK2 started to activate near -50 mV; IK1Cal started to activate near -35 mV. The time constant of removal of inactivation for IKA was 25 ms, measured at -80 mV, and that for IK1 was 380 ms, measured at -40 mV. 5. Tetraethylammonium acetate (TEA) allowed to diffuse from the inside of the recording microelectrode effectively blocked IKA, IK1, and IK2. Bath-applied TEA (25 mM) acted similarly but was less effective, particularly at blocking Ik2. Bath-applied 4-aminopyridine effectively blocked the transient currents IKA and IK1. A reversal potential of -65 mV was found for the outward currents, corresponding to a mix of IK1 and IK2.
Transfer characteristics of lateral geniculate nucleus X neurons in the cat: effects of spatial frequency and contrast
Authors: Cheng H. , Chino Y. M. , Smith E. L. , Hamamoto J. , Yoshida K.
Published: December 2017

1. The dependence of signal transfer in the lateral geniculate nucleus (LGN) on stimulus spatial frequency and contrast was investigated by comparing responses of individual X cells with their direct retinal inputs. 2. We used extracellular single-cell recording methods to isolate action potentials (LGN) and S potentials (SPs) from individual neurons in layers A and A1 of anesthetized and paralyzed cats. The stimuli were drifting sinusoidal gratings that were presented at each neuron's preferred orientation. The effects of stimulus spatial frequency and contrast on retinogeniculate signal transfer were determined by comparing the amplitude of the fundamental Fourier responses measured for a cell's action potentials (LGN) and its retinal input (SP) and calculating the transfer ratio (LGN amplitude/SP amplitude) for each stimulus condition. 3. In all units, the LGN response amplitude was lower than that of its retinal input regardless of stimulus spatial frequency. The mean transfer ratio measured at the peak spatial frequency for individual units was 0.56 +/- 0.03 (SE). For the majority of X LGN neurons, however, the efficiency of signal transfer varied considerably with stimulus spatial frequency. The average transfer ratio increased monotonically from 0.08 cycle/deg to near the high cutoff spatial frequency. 4. The effects of stimulus contrast on geniculate signal transfer were far more complex than previously reported and varied substantially between individual neurons. At low stimulus contrasts (< 10%), where all units exhibited linear response characteristics, only one third of our sample showed a monotonic decrease in transfer ratio with increasing stimulus contrast. The remaining two thirds either exhibited proportionately greater signal transfer for higher stimulus contrasts, or signal transfer remained relatively unchanged with increasing stimulus contrasts. When stimulus contrasts exceeded 10%, where response amplitude began to saturate, the transfer ratio was relatively constant in all units and independent of stimulus contrast. 5. Our results demonstrate that signal transfer from retina to visual cortex is regulated by LGN neurons in a stimulus-dependent manner, which appears to reflect the complex interactions between local membrane mechanisms and extraretinal inputs.
Widespread mechanosensory activation of the serotonergic system of the medicinal leech
Authors: Szczupak L. , Kristan W. B.
Published: December 2017

The serotonergic system of the medicinal leech comprises a small number of iterated, identified neurons, of which the Retzius (Rz) neurons are major components. Activity in pressure mechanosensory (P) cells sufficient to elicit locomotory and defensive behaviors also excites Rz neurons. We characterized the interactions between P and Rz neurons within the ganglion and at different distances along the nerve cord. 2. Within a ganglion 1) P cells excited both Rz neurons, electrically close to the site of electrical coupling between the Rz neurons; 2) each of the four P cells had similar effects on the Rz neurons; and 3) homologous contralateral P cells shared interneuronal pathways. These data show that P cells provide nearly identical bilateral information onto Rz neurons. 3. Along the nerve cord 1) every P cell excited Rz neurons in ganglia anterior and posterior to the site of stimulation; 2) the signal was carried the entire length of the nerve cord along interneuronal pathways with similar overall (but regionally different) conduction velocities in the two directions; 3) the amplitude of the Rz responses was smaller as the distance to the activated P cell increased; 4) the rate of change of the amplitude along the cord was larger when the signal traveled from front-to-back than in the opposite direction. 4. These data shows that mechanosensory input from any segment could excite Rz neurons along the cord, in proportion to the intensity of the stimulus.
Motor and somatosensory corticostriatal projection magnifications in the squirrel monkey
Authors: Flaherty A. W. , Graybiel A. M.
Published: December 2017

1. Motor and somatosensory cortex project massively to the primate striatal matrix, terminating in distributed sets of overlapping projection zones (matrisomes) within the putamen. To study this system quantitatively, we have developed a computer-assisted estimation of the changes in magnification that occur as motor and somatosensory cortical body representations are projected onto the putamen. 2. Cortical and striatal body maps were assessed in squirrel monkeys by injecting anterograde tract tracers into electrophysiologically identified body-part representations in cortical areas 4, 3a, 3b, and 1. Relative projection magnification was defined as the ratio of the cortical injection site volume to the striatal projection site volume. 3. Magnification comparisons indicate that the tracers wheat germ agglutinin-conjugated horseradish peroxidase (WGA-HRP) and 35S-methionine have similar sensitivities. 4. The relative proportions of body-part representations in the striatal maps were not significantly different from those in cortical maps. Both had large representations of hand, foot, and mouth, and smaller representations of trunk. 5. The relative magnification of the motor cortex projection to the striatum was roughly twice as large as those of projections from individual somatosensory areas. 6. These findings suggest that, in the sensorimotor striatum, motor and somatosensory inputs may undergo different proportions of local processing at the borders of their distribution zones (striosomes and matrisomes).
Simultaneous measurement of pH and membrane potential in rat dorsal vagal motoneurons during normoxia and hypoxia: a comparison in bicarbonate and HEPES buffers
Authors: Cowan A. I. , Martin R. L.
Published: December 2017

1. The effects of oxygenated and hypoxic bicarbonate/CO2, 10 and 25 mM N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid (HEPES)-buffered artificial cerebrospinal fluid (ACSF) have been studied in a rat brain slice preparation. Double-barreled pH-selective microelectrodes were used to measure intracellular pH (pHi) and membrane potential in dorsal vagal motoneurons (DVMs) and to measure extracellular pH (pHe) in the dorsal vagal motonucleus. 2. In bicarbonate ACSF, pHi averaged 7.24 +/- 0.05 (mean +/- SE, n = 21) and ranged from 6.86 to 7.79 pH units. pHe averaged 7.13 +/- 0.08 (n = 10). 3. On changing from oxygenated bicarbonate ACSF to either 10 or 25 mM HEPES ACSF, pHi decreased by 0.13-0.15 units, and the membrane depolarized by 10-11 mV. pHe also decreased in 10 mM HEPES ACSF (pHe 6.89 +/- 0.02, n = 8) but not in 25 mM HEPES ACSF (pHe 7.15 +/- 0.06, n = 3). In most neurons changes in pHi preceded changes in membrane potential. 4. In bicarbonate ACSF and in 25 mM HEPES ACSF, there was a significant linear relationship between prehypoxic pHi and the direction and amplitude of the hypoxia-induced membrane potential change (either an hyperpolarization or a depolarization). 5. In 10 mM HEPES ACSF, hypoxia always induced a depolarization; there was no correlation between prehypoxic pHi and the membrane potential response. 6. In bicarbonate ACSF and in 10 and 25 mM HEPES ACSF, hypoxia resulted in intracellular and extracellular acidification. However, the extracellular acidification in hypoxic 10 mM HEPES buffer was most pronounced (pH 6.40 +/- 0.11, n = 8), reflecting a preexisting extracellular acidification in oxygenated 10 mM HEPES buffer. 7. Various hypotheses that could give rise to a relationship between changes in membrane potential and pH are discussed; arguments are presented in favor of the concept that modulation of ion channels by either pHi or pHe, or both, is responsible for the observed correlations.
Identified octopaminergic neurons provide an arousal mechanism in the locust brain
Authors: Bacon J. P. , Thompson K. S. , Stern M.
Published: December 2017

1. Habituation is the declining responsiveness of a neural circuit (or behavior) to repetitive stimulation. Dishabituation (or arousal) can be brought about by the sudden presentation of an additional, novel stimulus. A clear example of arousal in the locust is provided by the visual system: the habituated response of the descending contralateral movement detector (DCMD) interneuron to repetitive visual stimuli can be dishabituated by a variety of other visual and tactile stimuli. 2. Application of octopamine to the locust brain and optic lobes dishabituates the DCMD in a manner similar to the effect of visual and tactile stimulation. 3. The locust CNS contains two pairs of octopamine-immunoreactive cells, the protocerebral medulla 4 (PM4) neurons, that could potentially mediate this dishabituation effect; PM4 neurons arborize in the optic lobe, they contain octopamine, and they respond to the same visual and tactile stimuli that dishabituate the DCMD. 4. To investigate whether PM4 activity dishabituates the DCMD, we recorded intracellularly from one of the PM4 neurons while recording extracellularly from the DCMD. When the PM4 neuron is injected with hyperpolarizing current to render it completely inactive, the DCMD exhibits its characteristic habituation to a moving visual stimulus. However, depolarizing the PM4 neuron, to produce action potentials at approximately 20 Hz, significantly increases the number of DCMD action potentials per stimulus. 5. The PM4 neurons may therefore play an important role in dishabituating the DCMD to novel stimuli. This effect is presumably mediated by PM4 neurons releasing endogenous octopamine within the optic lobe.
Frequency extent of two-tone facilitation in onset units in the ventral cochlear nucleus
Authors: Jiang D. , Palmer A. R. , Winter I. M.
Published: December 2017

1. The frequency threshold curves (FTCs) of 91 single units in the cochlear nucleus of the anesthetized guinea pig were measured using a conventional single-tone paradigm and a two-tone paradigm designed to elucidate the frequency extent of two-tone facilitation in onset units (On). Units were classified according to existing classification schemes into primary-like (n = 3), chopper (n = 23), and three onset groups: OnI (n = 12), OnC (n = 29), and OnL (n = 24). Histological reconstructions show onset units to be widely distributed within the ventral cochlear nucleus in a manner generally consistent with its tonotopic organization. 2. The FTCs of onset units differed in their minimum thresholds, the steepness of their high- and low-frequency cutoffs, and their sharpness of tuning as quantified by the quality factor at 10 dB (Q10dB) above best frequency (BF) threshold values. There was considerable overlap in the sharpness of tuning between onset units and auditory nerve fibers, as indicated by the distribution of Q10dB values in the octave around 10 kHz: onset units had Q10dB values of 3.56 +/- 1.38 (SD), compared with 6.3 +/- 2.48 for auditory nerve fibers. The tuning of chopper units was similar to that of auditory nerve fibers (5.52 +/- 1.46). 3. Seventy-five percent of onset units showed some degree of facilitation (a threshold reduction) when their FTCs were measured in the presence of BF tones 4 dB below BF threshold. The frequency extent of such facilitation was variable, with a maximum of 6 octaves around the BF. In extreme cases facilitation could be measured when the BF tone was as low as 30 dB below BF threshold. 4. In 17% of onset units, suppressive effects were evident, as shown by noncontiguous frequency regions of facilitation. These suppressive effects might be a reflection either of suppression in the auditory nerve input or of a direct inhibitory input to the onset units. The strength of this effect suggests that inhibition is a likely explanation, consistent with the finding in previous morphological studies of profuse synapses with pleomorphic vesicles on multipolar cells. 5. FTCs of chopper and primary-like units measured in the presence of BF tones showed little facilitation. The facilitation that was observed in chopper units was confined to a narrow region around BF and disappeared when the facilitatory tone was lowered to 4 dB below BF threshold. 6. These data support the hypothesis that onset units, but not chopper or primary-like units, receive excitatory inputs from auditory nerve fibers with a wide range of BFs. However, the frequency range of facilitation and the magnitude of the threshold facilitation varied from unit to unit, suggesting that the off-BF inputs from auditory nerve fibers are not evenly distributed or equally effective in all units.