bluuebunny/crossref_metadata_2025 huggingface dataset:
Developmental Changes in Hyperpolarization-Activated CurrentsI h and I K(IR) in Isolated Rat Intracardiac Neurons
Authors: Hogg R. C. , Harper A. A. , Adams D. J.
Published: December 2017

The hyperpolarization-activated nonselective cation current, I h, was investigated in neonatal and adult rat intracardiac neurons. I h was observed in all neurons studied and displayed slow time-dependent rectification. I h was isolated by blockade with external Cs+ (2 mM) and was inhibited irreversibly by the bradycardic agent, ZD 7288. Current density of I h was approximately twofold greater in neurons from neonatal (−4.1 pA/pF at −130 mV) as compared with adult (−2.3 pA/pF) rats; however, the reversal potential and activation parameters were unchanged. The reversal potential and amplitude of I h was sensitive to changes in external Na+ and K+ concentrations. An inwardly rectifying K+ current, I K(IR), was also present in intracardiac neurons from adult but not neonatal rats and was blocked by extracellular Ba2+. I K(IR) was present in approximately one-third of the adult intracardiac neurons studied, with a current density of −0.6 pA/pF at −130 mV. I K(IR) displayed rapid activation kinetics and no time-dependent rectification consistent with the rapidly activating, inward K+ rectifier described in other mammalian autonomic neurons. I K(IR) was sensitive to changes in external K+, whereby raising the external K+ concentration from 3 to 15 mM shifted the reversal potential by approximately +36 mV. Substitution of external Na+ had no effect on the reversal potential or amplitude of I K(IR). I K(IR) density increases as a function of postnatal development in a population of rat intracardiac neurons, which together with a concomitant decrease in I h may contribute to changes in the modulation of neuronal excitability in adult versus neonatal rat intracardiac ganglia.
Distinct Patterns of Brain Oscillations Underlie Two Basic Parameters of Human Maze Learning
Authors: Caplan Jeremy B. , Madsen Joseph R. , Raghavachari Sridhar , Kahana Michael J.
Published: December 2017

We examine how oscillations in the intracranial electroencephalogram (iEEG) relate to human maze learning. Theta- band activity (4–12 Hz in rodents; 4–8 Hz in humans) plays a significant role in memory function in rodents and in humans. Recording intracranially in humans, we have reported task-related, theta-band rhythmic activity in the raw trace during virtual maze learning and during a nonspatial working memory task. Here we analyze oscillations during virtual maze learning across a much broader range of frequencies and analyze their relationship to two task variables relevant to learning. We describe a new algorithm for detecting oscillatory episodes that takes advantage of the high signal-to-noise ratio and high temporal resolution of the iEEG. Accounting for the background power spectrum of the iEEG, the algorithm allows us to directly compare levels of oscillatory activity across frequencies within the 2- to 45-Hz band. We report that while episodes of oscillatory activity are found at various frequencies, most of the rhythmic activity during virtual maze learning occurs within the theta band. Theta oscillations are more prevalent when the task is made more difficult (manipulation of maze length). However, these oscillations do not tend to covary significantly with decision time, a good index of encoding and retrieval operations. In contrast, lower- and higher-frequency oscillations do covary with this variable. These results suggest that while human cortically recorded theta might play a role in encoding, the overall levels of theta oscillations tell us little about the immediate demands on encoding or retrieval. Finally, different patterns of oscillations may reflect distinct underlying aspects of memory function.
Pre-Bötzinger Neurons With Preinspiratory Discharges “In Vivo” Express NK1 Receptors in the Rat
Authors: Guyenet Patrice G. , Wang Hong
Published: December 2017

Substance P stimulates respiration, in part by a direct action on the pre-Bötzinger complex (preBötC). This region of the medulla oblongata contains neurons that are strongly immunoreactive for the neurokinin-1 receptor (NK1R-ir), and a recent theory has postulated that these cells might be the adult form of excitatory interneurons that are essential for respiratory rhythmogenesis in neonates. Here we sought to determine whether preBötC respiratory neurons are indeed NK1R-ir in the adult rat. Preinspiratory (pre-I) neurons were recorded in the preBötC region of halothane-anesthetized rats. Most pre-I cells could be antidromically activated from the contralateral side of the medulla (7 of 10; latency 1.3 ± 0.2 ms), suggesting that most of them were propriomedullary neurons rather than respiratory motoneurons or bulbospinal cells. Thirty-two pre-I neurons including seven cells with contralateral projection were labeled with biotinamide using the juxtacellular method. Eleven cells (34.4%) were NK1R-ir, including three of the seven pre-I cells that were antidromically activated from the contralateral side. In 3 control rats we labeled 20 preBötC neurons with patterns of discharge other than pre-I and found that none were detectably NK1R-ir. In conclusion, some of the intensely NK1R-ir neurons of the adult preBötC region are indeed respiratory interneurons as suggested by Gray et al. The subtype of NK1R identified by the antibody is detectable only in a small minority of preBötC respiratory cells, most notably in pre-I interneurons. Given prior anatomical evidence, these NK1R-ir pre-I interneurons are most likely glutamatergic. The data are consistent with the possibility that the NK1R-ir pre-I interneurons of the adult preBötC could be the adult form of a class of inspiratory neurons that are rhythmogenic in the neonate (either the pacemakers and/or an excitatory subtype of follower neurons).
Initiation and Propagation of Regenerative Ca2+-Dependent Potentials in Dendrites of Layer 5 Pyramidal Neurons
Authors: Oakley J. C. , Schwindt P. C. , Crill W. E.
Published: December 2017

The initiation and propagation of dendritic Ca2+-dependent regenerative potentials (CDRPs) were investigated by imaging the Ca2+-sensitive dye Fluo-4 during whole cell recording from the soma of layer 5 pyramidal neurons visualized in a slice preparation of rat neocortex by the use of infrared-differential interference contrast microscopy. CDRPs were evoked by focal iontophoresis of glutamate at visually identified sites 178–648 μm from the soma on the apical dendrite and at sites on the basal dendrites. Increases in [Ca2+]i were maximal near the site of iontophoresis and were graded with iontophoretic current that was subthreshold for evoking CDRPs. CDRP initiation was associated with a [Ca2+]i rise that differed from a just-subthreshold response in both magnitude and spatial extent but whose amplitude declined both proximal and distal to the iontophoretic site. These [Ca2+]i rises, whether associated with subthreshold or regenerative voltage responses, were minimally affected by blockade of N-methyl-d-aspartate receptors but were abolished by Cd2+, suggesting that Ca2+ influx through voltage-gated channels caused the rise of [Ca2+]i. On the assumption that the rise of [Ca2+]i during a CDRP marks the spatial extent of regenerative Ca2+influx, we conclude that CDRPs can be evoked at any point on the main apical or basal trunk where membrane potential reaches CDRP threshold rather than at discrete “hot spots,” the CDRP is initiated at a spatially restricted site, and it propagates decrementally both distal and proximal to its initiation site. These results raise the possibility that synaptic integration may occur first in the dendrites to evoke a CDRP. Because these responses propagate decrementally to the soma, they are able to sum with input from other regions of the cell so that the cell as a whole remains integrative.
Dendritic Mechanisms of Phase Precession in Hippocampal CA1 Pyramidal Neurons
Authors: Magee Jeffrey C.
Published: December 2017

Dual whole-cell patch clamp recordings from the soma and dendrites of CA1 pyramidal neurons located in hippocampal slices of adult rats were used to examine the potential mechanisms of phase precession. To mimic phasic synaptic input, 5-Hz sine wave current injections were simultaneously delivered both to the soma and apical dendrites (dendritic current was 180° out-of-phase with soma). Increasing the amplitude of the dendritic current injection caused somatic action potential initiation to advance in time (move forward up to 180°). The exact pattern of phase advancement is dependent on the dendritic location of input, with more distal input causing a more gradual temporal shift in spike initiation and a smaller increase in spike number. Patterned stimulation of Schaffer collateral/perforant path synaptic input can produce phase precession that is very similar to that observed with sine wave current injections. Finally, the exact amount of synaptic input required to produce phase advancement was found to be regulated by dendritic voltage-gated ion channels. Together, these data demonstrate that the summation of primarily proximal inhibition with an increasing amount of out-of-phase, primarily distal excitation can result in a form of phase advancement similar to that seen during theta activity in the intact hippocampus.
Broadly Tuned Spinal Neurons for Each Form of Fictive Scratching in Spinal Turtles
Authors: Berkowitz Ari
Published: December 2017

Behavioral choice can be mediated either by a small number of sharply tuned neurons or by large populations of broadly tuned neurons. This issue can be conveniently examined in the turtle spinal cord, which generates each of three forms of scratching—rostral, pocket, and caudal—in response to mechanical stimulation in each of three adjacent regions of the body surface. Previous research showed that many propriospinal neurons are broadly tuned to either the rostral scratch region or the pocket scratch region, but responses to caudal scratch stimulation could not be examined in that reduced preparation. In the current study, individual spinal neurons were recorded extracellularly from the gray matter of the turtle spinal cord hindlimb enlargement, while sites in the rostral, pocket, and caudal scratch regions were mechanically stimulated. Many neurons were broadly tuned to the caudal scratch region; other neurons were broadly tuned to either the pocket scratch or rostral scratch region. All three types were typically found within a single animal. These data are consistent with the hypothesis that the turtle spinal cord relies on large populations of broadly tuned neurons to select each of the three forms of scratching. In addition, neurons that were broadly tuned to each of the scratch regions were typically found in each spinal cord segment and within the same range of mediolateral and dorsoventral locations. Providing that these neurons are related to the selection and generation of the three forms of scratching, this would indicate that cells of this type are not segregated into distinct regions of the spinal cord gray matter.
Neurosteroids Mediate Habituation and Tonic Inhibition in the Auditory Midbrain
Authors: Disney Anita , Calford Mike B.
Published: December 2017

Habituation of the behavioral response to a repetitive stimulus is a well-established observation in perceptual studies and is considered a basic form of nonassociative learning. There is also a long history of physiological studies suggesting that central nervous system habituation is mediated by inhibition. At higher levels of the sensory pathways, such inhibition is mainly contributed by GABAa receptor mechanisms. Concepts of modification of synaptic efficacy that apply to excitatory amino acid synaptic transmission do not have direct parallels with these inhibitory synapses: quantal release of GABA rapidly saturates available receptors at a synapse, placing an upper limit on responsiveness to increased transmitter release. However, pharmacological modulation of GABAa-receptor efficacy with exogenous agents (e.g., benzodiazepines and β-carbolines) is known to occur through allosteric mechanisms that modulate the effectiveness (positive and negative) of GABA at this receptor. The most potent endogenous modulators are 5α-reduced steroids. Production of these steroids was attenuated in adult rats with systemic injection of Finasteride, a competitive substrate for 5α-reductase. This treatment was sufficient to block habituation of the evoked midbrain response to repetitive presentation of an acoustic click. This result confirms that simple habituation is due to an increase in active inhibition, the increase being mediated by steroid modulation of the GABAa-receptor. Finasteride treatment also brought about a 23% increase in the evoked response to a click stimulus, suggesting that 5α-reduced steroids normally contribute to tonic inhibition in the rat inferior colliculus.
Evidence for an Active Process and a Cochlear Amplifier in Nonmammals
Authors: Manley Geoffrey A.
Published: December 2017

The last two decades have produced a great deal of evidence that in the mammalian organ of Corti outer hair cells undergo active shape changes that are part of a “cochlear amplifier” mechanism that increases sensitivity and frequency selectivity of the hearing epithelium. However, many signs of active processes have also been found in nonmammals, raising the question as to the ancestry and commonality of these mechanisms. Active movements would be advantageous in all kinds of sensory hair cells because they help signal detection at levels near those of thermal noise and also help to overcome fluid viscosity. Such active mechanisms therefore presumably arose in the earliest kinds of hair cells that were part of the lateral line system of fish. These cells were embedded in a firm epithelium and responded to relative motion between the hair bundle and the hair cell, making it highly likely that the first active motor mechanism was localized in the hair-cell bundle. In terrestrial nonmammals, there are many auditory phenomena that are best explained by the presence of a cochlear amplifier, indicating that in this respect the mammalian ear is not unique. The latest evidence supports siting the active process in nonmammals in the hair-cell bundle and in intimate association with the transduction process.
Noise-Enhanced Heart Rate and Sympathetic Nerve Responses to Oscillatory Lower Body Negative Pressure in Humans
Authors: Hidaka Ichiro , Ando Shin-Ichi , Shigematsu Hideaki , Sakai Koji , Setoguchi Soko , Seto Taku , Hirooka Yoshitaka , Takeshita Akira , Yamamoto Yoshiharu
Published: December 2017

By injecting noise into the carotid sinus baroreceptors, we previously showed that heart rate (HR) responses to weak oscillatory tilt were enhanced via a mechanism known as “stochastic resonance.” It remains unclear, however, whether the same responses would be observed when using oscillatory lower body negative pressure (LBNP), which would unload the cardiopulmonary baroreceptors with physically negligible effects on the arterial system. Also, the vasomotor sympathetic activity directly controlling peripheral resistance against hypotensive stimuli was not observed. We therefore investigated the effects of weak (0 to approximately −10 mmHg) oscillatory (0.03 Hz) LBNP on HR and muscle sympathetic nerve activity (MSNA) while adding incremental noise to the carotid sinus baroreceptors via a pneumatic neck chamber. The signal-to-noise ratio of HR, cardiac interbeat interval, and total MSNA were all significantly improved by increasing noise intensity, while there was no significant change in the arterial blood pressure in synchronized with the oscillatory LBNP. We conclude that the stochastic resonance, affecting both HR and MSNA, results from the interaction of noise with the signal in the brain stem, where the neuronal inputs from the arterial and cardiopulmonary baroreceptors first come together in the nucleus tractus solitarius. Also, these results indicate that the noise could induce functional improvement in human blood pressure regulatory system in overcoming given hypotensive stimuli.
Two Virtual Fingers in the Control of the Tripod Grasp
Authors: Baud-Bovy Gabriel , Soechting John F.
Published: December 2017

To investigate the organization of multi-fingered grasping, we asked subjects to grasp an object using three digits: the thumb, the index finger, and the middle or ring finger. The object had three coarse flat contact surfaces, whose locations and orientations were varied systematically. Subjects were asked to grasp and lift the object and then to hold it statically. We analyzed the grasp forces in the horizontal plane that were recorded during the static hold period. Static equilibrium requires that the forces exerted by the three digits intersect at a common point, the force focus. The directions of the forces exerted by the two fingers opposing the thumb depended on the orientation of the contact surfaces of both fingers but not on the orientation of the contact surface of the thumb. The direction of the thumb's force did not depend on the orientation of the contact surfaces of the two fingers and depended only weakly on the orientation of the thumb's contact surface. In general, the thumb's force was directed to a point midway between the two fingers. The results are consistent with a hierarchical model of the control of a tripod grasp. At the first level, an opposition space is created between the thumb and a virtual finger located approximately midway between the two actual fingers. The directions of the forces exerted by the two fingers are constrained to be mirror symmetric about the opposition axis. The actual directions of finger force are elaborated at the next level on the basis of stability considerations.
Dependence of Saccade-Related Activity in the Primate Superior Colliculus on Visual Target Presence
Authors: Edelman Jay A. , Goldberg Michael E.
Published: December 2017

Neurons in the intermediate layers of the superior colliculus respond to visual targets and/or discharge immediately before and during saccades. These visual and motor responses have generally been considered independent, with the visual response dependent on the nature of the stimulus, and the saccade-related activity related to the attributes of the saccade, but not to how the saccade was elicited. In these experiments we asked whether saccade-related discharge in the superior colliculus depended on whether the saccade was directed to a visual target. We recorded extracellular activity of neurons in the intermediate layers of the superior colliculus of three rhesus monkeys during saccades in tasks in which we varied the presence or absence of a visual target and the temporal delays between the appearance and disappearance of a target and saccade initiation. Across our sample of neurons ( n = 64), discharge was highest when a saccade was made to a still-present visual target, regardless of whether the target had recently appeared or had been present for several hundred milliseconds. Discharge was intermediate when the target had recently disappeared and lowest when the target had never appeared during that trial. These results are consistent with the hypothesis that saccade-related discharge decreases as the time between the target disappearance and saccade initiation increases. Saccade velocity was also higher for saccades to visual targets, and correlated on a trial-by-trial basis with perisaccadic discharge for many neurons. However, discharge of many neurons was dependent on task but independent of saccade velocity, and across our sample of neurons, saccade velocity was higher for saccades made immediately after target appearance than would be predicted by discharge level. A tighter relationship was found between saccade precision and perisaccadic discharge. These findings suggest that just as the purpose of the saccadic system in primates is to drive the fovea to a visual target, presaccadic motor activity in the superior colliculus is most intense when such a target is actually present. This enhanced activity may, itself, contribute to the enhanced performance of the saccade system when the saccade is made to a real visual target.
Analysis of the Frequency Response of the Saccadic Circuit: System Behavior
Authors: Gnadt James W. , Jackson Mark E. , Litvak Oleg
Published: December 2017

To more thoroughly describe the system dynamics for the saccadic circuit in monkeys, we have determined the frequency response by applying a frequency modulated train of microstimulation pulses in the superior colliculus. The resulting eye movements reflect the transfer function of the saccadic circuit. Below input modulations of 5 cycles/s, the saccadic circuit increasingly oscillates with multiple high-frequency, low-amplitude movements reminiscent of the “staircase saccades” evoked during the sustained step response. Between 5 and 20 cycles/s, the circuit entrains well to the input, exhibiting one saccadic response to each sinusoidal input. Within this range there are systematic frequency-dependent changes in movement amplitudes, including super-normal saccades at some input frequencies. Above 20 cycles/s, the saccadic circuit increasingly exhibits periodic failures at rates of 1:2 or higher. In addition, the circuit exhibits predictable amplitude-modulated interference patterns in response to a combined step and frequency-modulated input. These experimental results provide insight into several biological mechanisms and serve as benchmark tests of viable models of the saccadic system. The data are consistent with negative feedback models of the saccadic system that operate as a displacement controller and inconsistent with theories that put the superior colliculus within the lowest-order, local feedback loop. The data support theories that the circuit feedback operates with dynamics that simulate a “leaky integrator.” In addition, the results demonstrate how the temporal output of the superior colliculus interacts with recurrent inhibition to influence the eye movement dynamics.
Mapping Pavlovian Conditioning Effects on the Brain: Blocking, Contiguity, and Excitatory Effects
Authors: Jones Dirk , Gonzalez-Lima F.
Published: December 2017

Pavlovian conditioning effects on the brain were investigated by mapping rat brain activity with fluorodeoxyglucose (FDG) autoradiography. The goal was to map the effects of the same tone after blocking or eliciting a conditioned emotional response (CER). In the tone-blocked group, previous learning about a light blocked a CER to the tone. In the tone-excitor group, the same pairings of tone with shock US resulted in a CER to the tone in the absence of previous learning about the light. A third group showed no CER after pseudorandom presentations of these stimuli. Brain systems involved in the various associative effects of Pavlovian conditioning were identified, and their functional significance was interpreted in light of previous FDG studies. Three conditioning effects were mapped: 1) blocking effects: FDG uptake was lower in medial prefrontal cortex and higher in spinal trigeminal and cuneate nuclei in the tone-blocked group relative to the tone-excitor group. 2) Contiguity effects: relative to pseudorandom controls, similar FDG uptake increases in the tone-blocked and -excitor groups were found in auditory regions (inferior colliculus and cortex), hippocampus (CA1), cerebellum, caudate putamen, and solitary nucleus. Contiguity effects may be due to tone-shock pairings common to the tone-blocked and -excitor groups rather than their different CER. And 3) excitatory effects: FDG uptake increases limited to the tone-excitor group occurred in a circuit linked to the CER, including insular and anterior cingulate cortex, vertical diagonal band nucleus, anterior hypothalamus, and caudoventral caudate putamen. This study provided the first large-scale map of brain regions underlying the Kamin blocking effect on conditioning. In particular, the results suggest that suppression of prefrontal activity and activation of unconditioned stimulus pathways are important neural substrates of the Kamin blocking effect.
Functional Analyses of the Leech Swim Oscillator
Authors: Friesen W. O. , Hocker C. G.
Published: December 2017

The oscillations that underlie swimming movements in the leech arise from a series of identified concatenated circuits within the ventral nerve cord. In the intact nerve cord, ascending and descending intersegmental interactions via axons within the lateral connectives function both to generate robust oscillations throughout the cord and to establish an anterior-to-posterior phase delay among segmental oscillators. We addressed two questions about this system. First, do the intrasegmental swim circuits in each ganglion function as a single oscillator or do they comprise a pair of coupled oscillators? Second, what are the relative strengths of the ascending and descending intersegmental interactions between the segmental oscillators? Experiments were carried out on semi-intact leeches ( Hirudo medicinalis) and on isolated leech nerve cords in which “Z-cut” ganglia were generated by cutting one lateral connective nerve anterior and the contralateral connective nerve posterior to the target ganglion. In these Z-cut ganglia, all rhythmic ascending intersegmental input is conveyed via one lateral connective while rhythmic descending input is conveyed via the contralateral connective. We found that rhythmic bursting recorded from the left and right sides of Z-cut ganglia had identical cycle periods with no phase difference, despite strong intersegmental inputs with differing periods from the two swimming ends of the preparations. We conclude that the swim circuits within individual leech ganglia act as single units. Moreover, we determined through correlation and Fourier spectral analyses, that the functional strengths of ascending and descending intersegmental inputs to Z-cut ganglia located in the middle of the nerve cord are approximately equal.
Differential Projections of Thermoreceptive and Nociceptive Lamina I Trigeminothalamic and Spinothalamic Neurons in the Cat
Authors: Craig A. D. , Dostrovsky J. O.
Published: December 2017

The projections of 40 trigeminothalamic or spinothalamic (TSTT) lamina I neurons were mapped using antidromic activation from a mobile electrode array in barbiturate anesthetized cats. Single units were identified as projection cells from the initial array position and characterized with natural cutaneous stimuli as nociceptive-specific (NS, n = 9), polymodal nociceptive (HPC, n = 8), or thermoreceptive-specific (COOL, n = 22; WARM, n = 1) cells. Thresholds for antidromic activation were measured from each electrode in the mediolateral array at vertical steps of 250 μm over a 7-mm dorsoventral extent in two to eight (median = 6.0) anteroposterior planes. Histological reconstructions showed that the maps encompassed all three of the main lamina I projection targets observed in prior anatomical work, i.e., the ventral aspect of the ventroposterior complex (vVP), the dorsomedial aspect of the ventroposterior medial nucleus (dmVPM), and the submedial nucleus (Sm). The antidromic activation foci were localized to these sites (and occasional projections to other sites were also observed, such as the parafascicular nucleus and zona incerta). The projections of thermoreceptive and nociceptive cells differed. The projections of the thermoreceptive-specific cells were 20/23 to dmVPM, 21/23 to vVP, and 17/23 to Sm, whereas the projections of the NS cells were 1/9 to dmVPM, 9/9 to vVP, and 9/9 to Sm and the projections of the HPC cells were 0/8 to dmVPM, 7/8 to vVP, and 6/8 to Sm. Thus nearly all thermoreceptive cells projected to dmVPM, but almost no nociceptive cells did. Further, thermoreceptive cells projected medially within vVP (including the basal ventral medial nucleus), while nociceptive cells projected both medially and more laterally, and the ascending axons of thermoreceptive cells were concentrated in the medial mesencephalon, while the axons of nociceptive cells ascended in the lateral mesencephalon. These findings provide evidence for anatomical differences between these physiological classes of lamina I cells, and they corroborate prior anatomical localization of the lamina I TSTT projection targets in the cat. These results support evidence indicating that the ventral aspect of the basal ventral medial nucleus is important for thermosensory behavior in cats, consistent with the view that this region is a primordial homologue of the posterior ventral medial nucleus in primates.
Transmission Security for Single, Hair Follicle–Related Tactile Afferent Fibers and Their Target Cuneate Neurons in Cat
Authors: Zachariah M. K. , Coleman G. T. , Mahns D. A. , Zhang H. Q. , Rowe M. J.
Published: December 2017

Transmission from single, identified hair follicle afferent (HFA) nerve fibers to their target neurons of the cuneate nucleus was examined in anesthetized cats by means of paired recording from individual cuneate neurons and from fine, intact fascicles of the lateral branch of the superficial radial nerve in which it is possible to identify and monitor the activity of each group II fiber. Selective activation of individual HFA fibers was achieved by means of focal vibrotactile skin stimulation. Forearm denervation precluded inputs from sources other than the monitored HFA sensory fiber. Transmission characteristics were analyzed for 21 HFA fiber-cuneate neuron pairs in which activity in the single HFA fiber of each pair reliably evoked spike output from the target neuron at a fixed latency. As the cuneate responses to each HFA impulse often consisted of 2 or 3 spikes, in particular at HFA input rates up to ∼20 imp/s, the synaptic linkage displayed potent amplification and high-gain transmission, characteristics that were confirmed quantitatively in measures of transmission security and cuneate spike output measures. In response to vibrotactile stimuli, the tight phase locking in the responses of single HFA fibers was well retained in the cuneate responses for vibration frequencies up to ∼200 Hz. On measures of vector strength, the phase locking declined across the synaptic linkage by no more than ∼10% at frequencies up to 100 Hz. However, limitations on the impulse rates generated in both the HFA fibers their associated cuneate neurons meant that the impulse patterns could not directly signal information about the vibration frequency above 50–100 Hz. Although single HFA fibers are also known to have secure synaptic linkages with spinocervical tract neurons, it is probable that this linkage lacks the capacity of the HFA-cuneate synapse for conveying precise temporal information, in an impulse pattern code, about the frequency parameter of vibrotactile stimuli.
Variations in Photoreceptor Response Dynamics Across the Fly Retina
Authors: Burton Brian G. , Tatler Ben W. , Laughlin Simon B.
Published: December 2017

Gradients in the spatial properties of retinal cells and their relation to image statistics are well documented. However, less is known of gradients in temporal properties, especially at the level of the photoreceptor for which no account exists. Using light flashes and white-noise-modulated light and current stimuli, we examined the spatial and temporal properties of a single class of photoreceptor (R1–6) within the compound eyes of male blowfly, Calliphora vicina. We find that there is a trend toward higher performance at the front of the eye, both in terms of spatiotemporal resolution and signal-to-noise ratio. The receptive fields of frontal photoreceptors are narrower than those of photoreceptors at the side and back of the eye and response speeds are 20% faster. The signal-to-noise ratio at high frequencies is also greatest at the front of the eye, allowing a 30–40% higher information rate. The power spectra of signals and noise indicate that this elevation of performance results both from shorter responses to individual photons and from a more reliable registration of photon arrival times. These distinctions are characteristic of adaptational changes that normally occur on increasing illumination. However, all photoreceptors were absorbing light at approximately the same mean photon rate during our recordings. We therefore suggest that frontal photoreceptors attain a higher state of light adaptation for a given photon rate. This difference may be achieved by a higher density of (Ca2+permeable) light-gated channels. Consistent with this hypothesis, membrane-impedance measurements show that frontal photoreceptors have a higher specific conductance than other photoreceptors. This higher conductance provides a better temporal performance but is metabolically expensive. Across the eye, temporal resolution is not proportional to spatial (optical) resolution. Neither is it matched obviously to optic flow. Instead we examine the consequences of an improved temporal resolution in the frontal region for the tracking of small moving targets, a behavior exhibited by male flies. We conclude that the temporal properties of a given class of retinal neuron can vary within a single retina and that this variation may be functionally related to the behavioral requirements of the animal.
Electrophysiological Evidence for Vasopressin V1Receptors on Neonatal Motoneurons, Premotor and Other Ventral Horn Neurons
Authors: Oz Murat , Kolaj Miloslav , Renaud Leo P.
Published: December 2017

Prominent arginine-vasopressin (AVP) binding and AVP V1 type receptors are expressed early in the developing rat spinal cord. We sought to characterize their influence on neural excitability by using patch-clamp techniques to record AVP-induced responses from a population of motoneurons and interneurons in neonatal (5–18 days) rat spinal cord slices. Data were obtained from 58 thoracolumbar (T7–L5) motoneurons and 166 local interneurons. A majority (>90%) of neurons responded to bath applied AVP (10 nM to 3 μM) and (Phe2, Orn8)-vasotocin, a V1receptor agonist, but not V2 or oxytocin receptor agonists. In voltage-clamp, postsynaptic responses in motoneurons were characterized by slowly rising, prolonged (7–10 min) and tetrodotoxin-resistant inward currents associated with a 25% reduction in a membrane potassium conductance that reversed near −100 mV. In interneurons, net AVP-induced inward currents displayed three patterns: decreasing membrane conductance with reversal near −100 mV, i.e., similar to that in motoneurons (24 cells); increasing conductance with reversal near −40 mV (21 cells); small reduction in conductance with no reversal within the current range tested (41 cells). A presynaptic component recorded in most neurons was evident as an increase in the frequency but not amplitude (in motoneurons) of inhibitory and excitatory postsynaptic currents (IPSCs and EPSCs), in large part due to AVP-induced firing in inhibitory (mainly glycinergic) and excitatory (glutamatergic) neurons synapsing on the recorded cells. An increase in frequency but not amplitude of miniature IPSCs and EPSCs also indicated an AVP enhancement of neurotransmitter release from axon terminals of inhibitory and excitatory interneurons. These observations provide support for a broad presynaptic and postsynaptic distribution of AVP V1 type receptors and indicate that their activation can enhance the excitability of a majority of neurons in neonatal ventral spinal cord.
Cellular Mechanisms for Amyloid β-Protein Activation of Rat Cholinergic Basal Forebrain Neurons
Authors: Jhamandas Jack H. , Cho Caroline , Jassar Balvinder , Harris Kim , MacTavish David , Easaw Jacob
Published: December 2017

The deposition of amyloid β-protein (Aβ) in the brain and the loss of cholinergic neurons in the basal forebrain are two pathological hallmarks of Alzheimer's disease (AD). Although the mechanism of Aβ neurotoxicity is unknown, these cholinergic neurons display a selective vulnerability when exposed to this peptide. In this study, application of Aβ25–35 or Aβ1–40 to acutely dissociated rat neurons from the basal forebrain nucleus diagonal band of Broca (DBB), caused a decrease in whole cell voltage-activated currents in a majority of cells. This reduction in whole cell currents occurs through a modulation of a suite of potassium conductances including calcium-activated potassium ( I C), the delayed rectifier ( I K), and transient outward potassium ( I A) conductances, but not calcium or sodium currents. Under current-clamp conditions, Aβ evoked an increase in excitability and a loss of accommodation in cholinergic DBB neurons. Using single-cell RT-PCR technique, we determined that Aβ actions were specific to cholinergic, but not GABAergic DBB neurons. Aβ effects on whole cell currents were occluded in the presence of membrane-permeable protein tyrosine kinase inhibitors, genistein and tyrphostin B-44. Our data indicate that the Aβ actions on specific potassium conductances are modulated through a protein tyrosine kinase pathway and that these effects are selective to cholinergic but not GABAergic cells. These observations provide a cellular basis for the selectivity of Aβ neurotoxicity toward cholinergic basal forebrain neurons that are at the epicenter of AD pathology.
Proprioceptive Modulation of Hip Flexor Activity During the Swing Phase of Locomotion in Decerebrate Cats
Authors: Lam Tania , Pearson Keir G.
Published: December 2017

This study examined the influence of proprioceptive input from hip flexor muscles on the activity in hip flexors during the swing phase of walking in the decerebrate cat. One hindlimb was partially denervated to remove cutaneous input and afferent input from most other hindlimb muscles. Perturbations to hip movement were applied either by 1) manual resistance or assistance to swing or by 2) resistance to hip flexion using a device that blocked hip flexion but allowed leg extension. Electromyographic recordings were made from the iliopsoas (IP), sartorius, and medial gastrocnemius muscles. When the hip was manually assisted into flexion, there was a reduction in hip flexor burst activity. Conversely, when hip flexion was manually resisted or mechanically blocked during swing, the duration and amplitude of hip flexor activity was increased. We also found some specificity in the role of afferents from individual hip flexor muscles in the modulation of flexor burst activity. If the IP muscle was detached from its insertion, little change in the response to blocking flexion was observed. Specific activation of IP afferent fibers by stretching the muscle also did not greatly affect flexor activity. On the other hand, if conduction in the sartorius nerves was blocked, there was a diminished response to blocking hip flexion. The increase in duration of the flexor bursts still occurred, but this increase was consistently lower than that observed when the sartorius nerves were intact. From these results we propose that during swing, feedback from hip flexor muscle afferents, particularly those from the sartorius muscles, enhances flexor activity. In addition, if we delayed the onset of flexor activity in the contralateral hindlimb, blocking hip flexion often resulted in the prolongation of ipsilateral flexor activity for long periods of time, further revealing the reinforcing effects of flexor afferent feedback on flexor activity. This effect was not seen if conduction in the sartorius nerves was blocked. In conclusion, we have found that hip flexor activity during locomotion can be strongly modulated by modifying proprioceptive feedback from the hip flexor muscles.
Role of NMDA, Non-NMDA, and GABA Receptors in Signal Propagation in the Amygdala Formation
Authors: Wang C. , Wilson W. A. , Moore S. D.
Published: December 2017

Although the synaptic physiology of the amygdala has been studied with single neuron recordings, the properties of the networks between the various nuclei have resisted characterization because of the limitations of field recording in a neuronally diffuse structure. We addressed this issue in the rat amygdala complex in vitro by using a photodiode array coupled with a voltage-sensitive dye. Low-intensity single pulse stimulation of the lateral amygdala nucleus produced a complex multi-phasic potential. This signal propagated to the basolateral nucleus and the amygdalostriatal transition zone but not to the central nucleus. The local potential, which depended on both synaptic responses and activation of voltage-dependent ion channels, was reduced in amplitude by the non– N-methyl-d-aspartate (non-NMDA) glutamate receptor antagonist 6,7-dinitroquinoxaline (DNQX) and reduced to a lesser extent by the NMDA glutamate receptor antagonistd-2-amino-5-phosphonovaleric acid (d-APV). We next characterized the less complex signals that propagated to more distal regions with or without the addition of the GABA receptor antagonist bicuculline (BIC). BIC alone greatly increased the signal propagation and permitted activation of previously silent areas within the amygdala. DNQX blocked signal propagation to amygdala regions outside of La, even in the presence of BIC, whereas d-APV had minimal effects on these distal signals. These data represent several novel findings: the characterization of the multi-component potential near the site of stimulation, the gating of signal propagation within the amygdala by GABAergic inhibition, the critical role of non-NMDA receptor–mediated depolarization in signal propagation, and the lack of a role for NMDA receptors in maintaining propagation.
Mechanisms That Initiate Spontaneous Network Activity in the Developing Chick Spinal Cord
Authors: Wenner Peter , O'Donovan Michael J.
Published: December 2017

Many developing networks exhibit a transient period of spontaneous activity that is believed to be important developmentally. Here we investigate the initiation of spontaneous episodes of rhythmic activity in the embryonic chick spinal cord. These episodes recur regularly and are separated by quiescent intervals of many minutes. We examined the role of motoneurons and their intraspinal synaptic targets (R-interneurons) in the initiation of these episodes. During the latter part of the inter-episode interval, we recorded spontaneous, transient ventral root depolarizations that were accompanied by small, spatially diffuse fluorescent signals from interneurons retrogradely labeled with a calcium-sensitive dye. A transient often could be resolved at episode onset and was accompanied by an intense pre-episode (∼500 ms) motoneuronal discharge (particularly in adductor and sartorius) but not by interneuronal discharge monitored from the ventrolateral funiculus (VLF). An important role for this pre-episode motoneuron discharge was suggested by the finding that electrical stimulation of motor axons, sufficient to activate R-interneurons, could trigger episodes prematurely. This effect was mediated through activation of R-interneurons because it was prevented by pharmacological blockade of either the cholinergic motoneuronal inputs to R-interneurons or the GABAergic outputs from R-interneurons to other interneurons. Whole-cell recording from R-interneurons and imaging of calcium dye-labeled interneurons established that R-interneuron cell bodies were located dorsomedial to the lateral motor column (R-interneuron region). This region became active before other labeled interneurons when an episode was triggered by motor axon stimulation. At the beginning of a spontaneous episode, whole-cell recordings revealed that R-interneurons fired a high-frequency burst of spikes and optical recordings demonstrated that the R-interneuron region became active before other labeled interneurons. In the presence of cholinergic blockade, however, episode initiation slowed and the inter-episode interval lengthened. In addition, optical activity recorded from the R-interneuron region no longer led that of other labeled interneurons. Instead the initial activity occurred bilaterally in the region medial to the motor column and encompassing the central canal. These findings are consistent with the hypothesis that transient depolarizations and firing in motoneurons, originating from random fluctuations of interneuronal synaptic activity, activate R-interneurons, which then trigger the recruitment of the rest of the spinal interneuronal network. This unusual function for R-interneurons is likely to arise because the output of these interneurons is functionally excitatory during development.
Model of Gamma Frequency Burst Discharge Generated by Conditional Backpropagation
Authors: Doiron Brent , Longtin André , Turner Ray W. , Maler Leonard
Published: December 2017

Pyramidal cells of the electrosensory lateral line lobe (ELL) of the weakly electric fish Apteronotus leptorhynchus have been shown to produce oscillatory burst discharge in the γ-frequency range (20–80 Hz) in response to constant depolarizing stimuli. Previous in vitro studies have shown that these bursts arise through a recurring spike backpropagation from soma to apical dendrites that is conditional on the frequency of action potential discharge (“conditional backpropagation”). Spike bursts are characterized by a progressive decrease in inter-spike intervals (ISIs), and an increase of dendritic spike duration and the amplitude of a somatic depolarizing afterpotential (DAP). The bursts are terminated when a high-frequency somatic spike doublet exceeds the dendritic spike refractory period, preventing spike backpropagation. We present a detailed multi-compartmental model of an ELL basilar pyramidal cell to simulate somatic and dendritic spike discharge and test the conditions necessary to produce a burst output. The model ionic channels are described by modified Hodgkin-Huxley equations and distributed over both soma and dendrites under the constraint of available immunocytochemical and electrophysiological data. The currents modeled are somatic and dendritic sodium and potassium involved in action potential generation, somatic and proximal apical dendritic persistent sodium, and KV3.3 and fast transient A-like potassium channels distributed over the entire model cell. The core model produces realistic somatic and dendritic spikes, differential spike refractory periods, and a somatic DAP. However, the core model does not produce oscillatory spike bursts with constant depolarizing stimuli. We find that a cumulative inactivation of potassium channels underlying dendritic spike repolarization is a necessary condition for the model to produce a sustained γ-frequency burst pattern matching experimental results. This cumulative inactivation accounts for a frequency-dependent broadening of dendritic spikes and results in a conditional failure of backpropagation when the intraburst ISI exceeds dendritic spike refractory period, terminating the burst. These findings implicate ion channels involved in repolarizing dendritic spikes as being central to the process of conditional backpropagation and oscillatory burst discharge in this principal sensory output neuron of the ELL.