bluuebunny/crossref_metadata_2025 huggingface dataset:
Activation and Reconfiguration of Fictive Feeding by the OctopamineContaining Modulatory OC Interneurons in the SnailLymnaea
Authors: Vehovszky Ágnes , Elliott Christopher J. H.
Published: December 2017

We describe the role of the octopamine-containing OC interneurons in the buccal feeding system of Lymnaea stagnalis. OC neurons are swallowing phase interneurons receiving inhibitory inputs in the N1 and N2 phases, and excitatory inputs in the N3 phase of fictive feeding. Although the OC neurons do not always fire during feeding, the feeding rate is significantly ( P < 0.001) higher when both SO and OC fire in each cycle than when only the SO fires. In 28% of silent preparations, a single stimulation of an OC interneuron evokes the feeding pattern. Repetitive stimulation of the OC interneuron increases the proportion of responsive preparations to 41%. The OC interneuron not only changes both the feeding rate and reconfigures the pattern. Depolarization of the OC interneurons increases the feeding rate and removes the B3 motor neuron from the firing sequence. Hyperpolarization slows it down (increasing the duration of N1 and N3 phases) and recruits the B3 motor neuron. OC interneurons form synaptic connections onto buccal motor neurons and interneurons but not onto the cerebral (cerebral giant cell) modulatory neurons. OC interneurons are electrically coupled to all N3 phase (B4, B4Cl, B8) feeding motor neurons. They form symmetrical connections with the N3p interneurons having dual electrical (excitatory) and chemical (inhibitory) components. OC interneurons evoke biphasic synaptic inputs on the protraction phase interneurons (SO, N1L, N1M), with a short inhibition followed by a longer lasting depolarization. N2d interneurons are hyperpolarized, while N2v interneurons are slowly depolarized and often fire a burst after OC stimulation. Most motor neurons also receive synaptic responses from the OC interneurons. Although OC and N3p interneurons are both swallowing phase interneurons, their synaptic contacts onto follower neurons are usually different (e.g., the B3 motor neurons are inhibited by OC, but excited by N3p interneurons). Repetitive stimulation of OC interneuron facilitates the excitatory component of the biphasic responses evoked on the SO, N1L, and N1M interneurons, but neither the N2 nor the N3 phase interneurons display a similar longer-lasting excitatory effect. OC interneurons are inhibited by all the buccal feeding interneurons, but excited by the serotonergic modulatory CGC neurons. We conclude that OC interneurons are a new kind of swallowing phase interneurons. Their connections with the buccal feeding interneurons can account for their modulatory effects on the feeding rhythm. As they contain octopamine, this is the first example in Lymnaea that monoaminergic modulation and reconfiguration are provided by an intrinsic member of the buccal feeding network.
Ocular Counterroll Modulates the Preferred Direction of Saccade-Related Pontine Burst Neurons in the Monkey
Authors: Scherberger Hansjörg , Cabungcal Jan-Harry , Hepp Klaus , Suzuki Yasuo , Straumann Dominik , Henn Volker
Published: December 2017

Saccade-related burst neurons in the paramedian pontine reticular formation (PPRF) of the head-restrained monkey provide a phasic velocity signal to extraocular motoneurons for the generation of rapid eye movements. In the superior colliculus (SC), which directly projects to the PPRF, the motor command for conjugate saccades with the head restrained in a roll position is represented in a reference frame in between oculocentric and space-fixed coordinates with a clear bias toward gravity. Here we studied the preferred direction of premotor burst neurons in the PPRF during static head roll to characterize their frame of reference with respect to head and eye position. In 59 neurons (short-lead, burst-tonic, and long-lead burst neurons), we found that the preferred direction of eye displacement of these neurons changed, relative to head-fixed landmarks, in the horizontal-vertical plane during static head roll. For the short-lead burst neurons and the burst-tonic group, the change was about one-fourth of the amount of ocular counterroll (OCR) and significantly different from a head-centered representation. In the long-lead burst neurons, the rotation of the preferred direction showed a larger trend of about one-half of OCR. During microelectrical stimulation of the PPRF (9 sites in 2 monkeys), the elicited eye movements rotated with about one-half the amount of OCR. In a simple pulley model of the oculomotor plant, the noncraniocentric reference frame of the PPRF output neurons could be reproduced for recently measured pulley positions, if the pulleys were assumed to rotate as a function of OCR with a gain of 0.5. We conclude that the saccadic displacement signal is transformed from a representation in the SC with a clear bias to gravity to a representation in the PPRF that is closely craniocentric, but rotates with OCR, consistent with current concepts of the oculomotor plant.
Activity in Ventral and Dorsal Premotor Cortex in Response to Predictable Force-Pulse Perturbations in a Precision Grip Task
Authors: Boudreau Marie-Josée , Brochier Thomas , Paré Michel , Smith Allan M.
Published: December 2017

This study compared the responses of ventral and dorsal premotor cortex (PMv and PMd) neurons to predictable force-pulse perturbations applied during a precision grip. Three monkeys were trained to grasp an unseen instrumented object between the thumb and index finger and to lift and hold it stationary within a position window for 2–2.5 s. The grip and load forces and the object displacement were measured on each trial. Single-unit activity was recorded from the hand regions in the PMv and PMd. In some conditions a predictable perturbation was applied to the object after 1,500 ms of static holding, whereas in other conditions different random combinations of perturbed and unperturbed trials were given. In the perturbed conditions, some were randomly and intermittently presented with a warning flash, whereas some were unsignaled. The activities of 198 cells were modulated during the task performance. Of these cells, 151 were located in the PMv, and 47 were located in the PMd. Although both PMv and PMd neurons had similar discharge patterns, more PMd neurons (84 vs. 43%) showed early pregrip activity. Forty of 106 PMv and 10/30 PMd cells responded to the perturbation with reflexlike triggered reactions. The latency of this response was always <100 ms with a mean of about 55 ms in both the PMv and the PMd. In contrast, 106 PMv and 30 PMd cells tested with the perturbations, only 9 and 10%, respectively, showed significant but nonspecific adaptations to the perturbation. The warning stimulus did not increase the occurrence of specific responses to the perturbation even though 21 of 42 cells related to the grip task also responded to moving visual stimuli. The responses were retinal and frequently involved limited portions of both foveal and peripheral visual fields. When tested with a 75 × 5.5-cm dark bar on a light background, these cells were sensitive to the direction of movement. In summary, the periarcuate premotor area activity to related to predictable force-pulse perturbations seems to reflect a general increase in excitability in contrast to a more specific anticipatory activity such as recorded in the cerebellum. In spite of the strong cerebello-thalamo-cortical projections, the results of the present study suggest that the cortical premotor areas are not involved in the elaboration of adaptive internal models of hand-object dynamics.
Responses of Auditory Cortical Neurons to Pairs of Sounds: Correlates of Fusion and Localization
Authors: Mickey Brian J. , Middlebrooks John C.
Published: December 2017

When two brief sounds arrive at a listener's ears nearly simultaneously from different directions, localization of the sounds is described by “the precedence effect.” At inter-stimulus delays (ISDs) <5 ms, listeners typically report hearing not two sounds but a single fused sound. The reported location of the fused image depends on the ISD. At ISDs of 1–4 ms, listeners point near the leading source (localization dominance). As the ISD is decreased from 0.8 to 0 ms, the fused image shifts toward a location midway between the two sources (summing localization). When an inter-stimulus level difference (ISLD) is imposed, judgements shift toward the more intense source. Spatial hearing, including the precedence effect, is thought to depend on the auditory cortex. Therefore we tested the hypothesis that the activity of cortical neurons signals the perceived location of fused pairs of sounds. We recorded the unit responses of cortical neurons in areas A1 and A2 of anesthetized cats. Single broadband clicks were presented from various frontal locations. Paired clicks were presented with various ISDs and ISLDs from two loudspeakers located 50° to the left and right of midline. Units typically responded to single clicks or paired clicks with a single burst of spikes. Artificial neural networks were trained to recognize the spike patterns elicited by single clicks from various locations. The trained networks were then used to identify the locations signaled by unit responses to paired clicks. At ISDs of 1–4 ms, unit responses typically signaled locations near that of the leading source in agreement with localization dominance. Nonetheless the responses generally exhibited a substantial undershoot; this finding, too, accorded with psychophysical measurements. As the ISD was decreased from ∼0.4 to 0 ms, network estimates typically shifted from the leading location toward the midline in agreement with summing localization. Furthermore a superposed ISLD shifted network estimates toward the more intense source, reaching an asymptote at an ISLD of 15–20 dB. To allow quantitative comparison of our physiological findings to psychophysical results, we performed human psychophysical experiments and made acoustical measurements from the ears of cats and humans. After accounting for the difference in head size between cats and humans, the responses of cortical units usually agreed with the responses of human listeners, although a sizable minority of units defied psychophysical expectations.
Circadian Force and EMG Activity in Hindlimb Muscles of Rhesus Monkeys
Authors: Hodgson J. A. , Wichayanuparp S. , Recktenwald M. R. , Roy R. R. , McCall G. , Day M. K. , Washburn D. , Fanton J. W. , Kozlovskaya I. , Edgerton V. R.
Published: December 2017

Continuous intramuscular electromyograms (EMGs) were recorded from the soleus (Sol), medial gastrocnemius (MG), tibialis anterior (TA), and vastus lateralis (VL) muscles of Rhesus during normal cage activity throughout 24-h periods and also during treadmill locomotion. Daily levels of MG tendon force and EMG activity were obtained from five monkeys with partial datasets from three other animals. Activity levels correlated with the light-dark cycle with peak activities in most muscles occurring between 08:00 and 10:00. The lowest levels of activity generally occurred between 22:00 and 02:00. Daily EMG integrals ranged from 19 mV/s in one TA muscle to 3339 mV/s in one Sol muscle: average values were 1245 (Sol), 90 (MG), 65 (TA), and 209 (VL) mV/s. The average Sol EMG amplitude per 24-h period was 14 μV, compared with 246 μV for a short burst of locomotion. Mean EMG amplitudes for the Sol, MG, TA, and VL during active periods were 102, 18, 20, and 33 μV, respectively. EMG amplitudes that approximated recruitment of all fibers within a muscle occurred for 5–40 s/day in all muscles. The duration of daily activation was greatest in the Sol [151 ± 45 (SE) min] and shortest in the TA (61 ± 19 min). The results show that even a “postural” muscle such as the Sol was active for only ∼9% of the day, whereas less active muscles were active for ∼4% of the day. MG tendon forces were generally very low, consistent with the MG EMG data but occasionally reached levels close to estimates of the maximum force generating potential of the muscle. The Sol and TA activities were mutually exclusive, except at very low levels, suggesting very little coactivation of these antagonistic muscles. In contrast, the MG activity usually accompanied Sol activity suggesting that the MG was rarely used in the absence of Sol activation. The results clearly demonstrate a wide range of activation levels among muscles of the same animal as well as among different animals during normal cage activity.
Spike Coding in Pyramidal Cells of the Piriform Cortex of Rat
Authors: Protopapas Alexander D. , Bower James M.
Published: December 2017

The study of cortical oscillations has undergone a renaissance in recent years because of their presumed role in cognitive function. Of particular interest are frequencies in the gamma (30–100 Hz) and theta (3–12 Hz) ranges. In this paper, we use spike coding techniques and in vitro whole cell recording to assess the ability of individual pyramidal cells of the piriform cortex to code inputs occurring in these frequencies. The results suggest that the spike trains of individual neurons are much better at representing frequencies in the theta range than those in the gamma range.
Characterization of Reliability of Spike Timing in Spinal Interneurons During Oscillating Inputs
Authors: Beierholm Ulrik , Nielsen Carsten D. , Ryge Jesper , Alstrøm Preben , Kiehn Ole
Published: December 2017

The spike timing in rhythmically active interneurons in the mammalian spinal locomotor network varies from cycle to cycle. We tested the contribution from passive membrane properties to this variable firing pattern, by measuring the reliability of spike timing, P, in interneurons in the isolated neonatal rat spinal cord, using intracellular injection of sinusoidal command currents of different frequencies (0.325–31.25 Hz). P is a measure of the precision of spike timing. In general, P was low at low frequencies and amplitudes ( P = 0–0.6; 0–1.875 Hz; 0–30 pA), and high at high frequencies and amplitudes ( P = 0.8–1; 3.125–31.25 Hz; 30–200 pA). The exact relationship between P and amplitude was difficult to describe because of the well-known low-pass properties of the membrane, which resulted in amplitude attenuation of high-frequency compared with low-frequency command currents. To formalize the analysis we used a leaky integrate and fire (LIF) model with a noise term added. The LIF model was able to reproduce the experimentally observed properties of P as well as the low-pass properties of the membrane. The LIF model enabled us to use the mathematical theory of nonlinear oscillators to analyze the relationship between amplitude, frequency, and P. This was done by systematically calculating the rotational number, N, defined as the number of spikes divided by the number of periods of the command current, for a large number of frequencies and amplitudes. These calculations led to a phase portrait based on the amplitude of the command current versus the frequency-containing areas [Arnold tongues (ATs)] with the same rotational number. The largest ATs in the phase portrait were those where N was a whole integer, and the largest areas in the ATs were seen for middle to high (>3 Hz) frequencies and middle to high amplitudes (50–120 pA). This corresponded to the amplitude- and frequency-evoked increase in P. The model predicted that P would be high when a cell responded with an integer and constant N. This prediction was confirmed by comparing N and P in real experiments. Fitting the result of the LIF model to the experimental data enabled us to estimate the standard deviation of the internal neuronal noise and to use these data to simulate the relationship between N and P in the model. This simulation demonstrated a good correspondence between the theoretical and experimental values. Our data demonstrate that interneurons can respond with a high reliability of spike timing, but only by combining fast and slow oscillations is it possible to obtain a high reliability of firing during rhythmic locomotor movements. Theoretical analysis of the rotation number provided new insights into the mechanism for obtaining reliable spike timing.
Neural and Mechanical Factors in Eye Control
Authors: Misslisch H. , Tweed D.
Published: December 2017

Soft tissue “pulleys” in the orbit alter the paths of the eye muscles in a way that may simplify the brain's work in implementing Listing's law, i.e., in holding ocular torsion at zero. But Listing's law does not apply to some oculomotor systems, such as the vestibuloocular reflex (VOR), which shows a different kinematic pattern. To explain this different pattern, some authors have assumed that the pulleys must adopt a different configuration, retracting along their muscles when the eye switches from Listing's law to VOR mode. The proposed retraction has not so far been observed, although the pulleys do move in other ways. We show that the hypothetical retraction of the pulleys would not in fact explain the full kinematic pattern seen in the VOR. But this pattern can be explained entirely on the basis of pulley positions and motions that have actually been observed. If one takes into account the neural processing within the VOR, specifically the fact that the reflex is weak in the torsional dimension, then a single mode of pulley action can serve both vestibuloocular kinematics and Listing's law.
Evidence for Plateau Potentials in Tail Motoneurons of Awake Chronic Spinal Rats With Spasticity
Authors: Bennett David J. , Li Yunru , Harvey Philip J. , Gorassini Monica
Published: December 2017

Motor units of segmental tail muscles were recorded in awake rats following acute (1–2 days) and chronic (>30 days) sacral spinal cord transection to determine whether plateau potentials contributed to sustained motor-unit discharges after injury. This study was motivated by a companion in vitro study that indicated that after chronic spinal cord injury, the tail motoneurons of the sacrocaudal spinal cord exhibit persistent inward currents ( I PIC) that cause intrinsically sustained depolarizations ( plateau potentials) and firing ( self-sustained firing). Importantly, in this companion study, the plateaus were fully activated at recruitment and subsequently helped sustain the firing without causing abrupt nonlinearities in firing. That is, after recruitment and plateau activation, the firing rate was modulated relatively linearly with injected current and therefore provided a good approximation of the input to the motoneuron despite the plateau. Thus in the present study, pairs of motor units were recorded simultaneously from the same muscle, and the firing rate ( F) of the lowest-threshold unit (control unit) was used as an estimate of the synaptic input to both units. We then examined whether firing of the higher-threshold unit (test unit) was intrinsically maintained by a plateau, by determining whether more synaptic input was required to recruit the test unit than to maintain its firing. The difference in the estimated synaptic input at recruitment and de-recruitment of the test unit (i.e., change in control unit rate, Δ F) was taken as an estimate of the plateau current ( I PIC) that intrinsically sustained the firing. Slowly graded manual skin stimulation was used to recruit and then de-recruit the units. The test unit was recruited when the control unit rate was on average 17.8 and 18.9 Hz in acute and chronic spinal rats, respectively. In chronic spinal rats, the test unit was de-recruited when the control unit rate (re: estimated synaptic input) was significantly reduced, compared with at recruitment (Δ F = −5.5 Hz), and thus a plateau participated in maintaining the firing. In the lowest-threshold motor units, even a brief stimulation triggered very long-lasting firing (seconds to hours; self-sustained firing). Higher-threshold units required continuous stimulation (or a spontaneous spasm) to cause firing, but again more synaptic input was needed to recruit the unit than to maintain its firing (i.e., plateau present). In contrast, in acute spinal rats, the stimulation did not usually trigger sustained motor-unit firing that could be attributed to plateaus because Δ F was not significantly different from zero. These results indicate that plateaus play an important role in sustaining motor-unit firing in awake chronic spinal rats and thus contribute to the hyperreflexia and hypertonus associated with chronic injury.
Functional Properties of Single Motor Units in Inferior Head of Human Lateral Pterygoid Muscle: Task Relations and Thresholds
Authors: Phanachet I. , Whittle T. , Wanigaratne K. , Murray G. M.
Published: December 2017

The aim of this study was to clarify the normal function of the inferior head of the human lateral pterygoid muscle (IHLP). The hypothesis was that an important function of the IHLP is in the fine control of horizontal jaw movements. The activities of 99 single motor units (SMUs) were recorded from IHLP (22 recordings from 16 subjects). Most recording sites were identified by computer tomography (CT). All 99 SMUs were active during contralateral jaw movements with the teeth apart, and protrusive jaw movements with the teeth apart, and 81% (48 of 59 units studied during all 3 tasks) were active during submaximal jaw-opening movements. None were active on maximal ipsilateral or retrusive jaw movements with the teeth apart nor on jaw closing/clenching in intercuspal position; nor were they spontaneously active when the jaw was at the clinically determined postural jaw position. Thresholds of SMUs ranged from <0.2 mm of contralateral or protrusive horizontal displacements to 61–89% of the maximum contralateral or protrusive displacement, respectively. For the 35 units continuously active during the contralateral task, 23 (66%) were recruited within 2 mm of contralateral displacement [25 (63% of 40 units) for protrusion]. Recruitment thresholds (mm) of some of the units were rate dependent with thresholds significantly decreasing with increasing rate of horizontal jaw movement in protrusion and contralateral movements. At eight recording sites where up to six SMUs were able to be discriminated, the average thresholds of successively recruited SMUs were within a 1-mm increment of horizontal jaw displacement. After dividing IHLP into four regions, the SMUs recorded in the superior-medial zone exhibited significantly lower mean threshold values than for the SMUs recorded in the other zones (no units were recorded in the inferior-lateral zone). This provides suggestive evidence supporting previously proposed notions of functional heterogeneity within IHLP. Taken together, the data suggest that specific regions of the IHLP are capable of selective activation in a finely controlled manner to allow the application of the appropriate force vector (magnitude and direction) to effect the required condylar movement needed for the generation and control of horizontal jaw movements.
Disruption of Inhibition in Area CA1 of the Hippocampus in a Rat Model of Temporal Lobe Epilepsy
Authors: Denslow Maria J. , Eid Tore , Du Fu , Schwarcz Robert , Lothman Eric W. , Steward Oswald
Published: December 2017

Previous studies have revealed a loss of neurons in layer III of the entorhinal cortex (EC) in patients with temporal lobe epilepsy. These neurons project to the hippocampus and may activate inhibitory interneurons, so that their loss could disrupt inhibitory function in the hippocampus. The present study evaluates this hypothesis in a rat model in which layer III neurons were selectively destroyed by focal injections of the indirect excitotoxin, aminooxyacetic acid (AOAA). Inhibitory function in the hippocampus was assessed by evaluating the discharge of CA1 neurons in response to stimulation of afferent pathways in vivo. In control animals, stimulation of the temporo-ammonic pathway leads to heterosynaptic inhibition of population spikes generated by subsequent stimulation of the commissural projection to CA1. This heterosynaptic inhibition was substantially reduced in animals that had received AOAA injections 1 mo previously. Stimulation of the commissural projection also elicited multiple population spikes in CA1 in AOAA-injected animals, and homosynaptic inhibition in response to paired-pulse stimulation of the commissural projection was dramatically diminished. These results suggest a disruption of inhibitory function in CA1 in AOAA-injected animals. To determine whether the disruption of inhibition occurred selectively in CA1, we assessed paired-pulse inhibition in the dentate gyrus. Both homosynaptic inhibition generated by paired-pulse stimulation of the perforant path, and heterosynaptic inhibition produced by activation of the commissural projection to the dentate gyrus appeared largely comparable in AOAA-injected and control animals; thus abnormalities in inhibitory function following AOAA injections occurred relatively selectively in CA1. Electrolytic lesions of the EC did not cause the same loss of inhibition as seen in animals with AOAA injections, indicating that the loss of inhibition in CA1 is not due to the loss of excitatory driving of inhibitory interneurons. Also, electrolytic lesions of the EC in animals that had been injected previously with AOAA had little effect on the abnormal physiological responses in CA1, suggesting that most alterations in inhibition in CA1 are not due to circuit abnormalities within the EC. Comparisons of control and AOAA-injected animals in a hippocampal kindling paradigm revealed that the duration of afterdischarges elicited by high-frequency stimulation of CA3, and the number of stimulations required to elicit kindled seizures were comparable. Taken together, our results reveal that the selective loss of layer III neurons induced by AOAA disrupts inhibitory function in CA1, but this does not create a circuit that is more prone to at least one form of kindling.
Ocular Responses to Head Rotations During Mirror Viewing
Authors: Han Yanning , Somers Jeffrey T. , Kim Jae I. , Kumar Arun N. , Leigh R. John
Published: December 2017

The gain of the human vestibuloocular reflex (VOR) is influenced by the proximity of the object of regard. In six human subjects, we measured the eye rotations induced by passive, sinusoidal, horizontal head rotations at 2.0 Hz during binocular fixation of a stationary far target at 7 m; a stationary target close to the subject's near point of fixation (<15 cm); and the bridge of the subject's own nose, viewed through a mirror positioned so that, for each subject, the angle of vergence was similar to that during viewing of the near target. The median gain of compensatory eye movements for the group of subjects during far viewing was 0.99 (range 0.80–1.04), during near viewing was 1.21 (range 0.88–1.47), and during mirror viewing was 0.85 (range 0.71–1.01). The gain during near and mirror viewing was significantly different for each subject ( P < 0.001) even though the vergence angles were similar. The lower gain values during mirror viewing can be attributed to the geometric relationship between the head rotation, the position of the eyes in the head, and the movement of the subject's virtual image in the mirror. To determine whether visually mediated eye movements were responsible for the observed gain values, we conducted a control experiment in which subjects were rotated using a sum-of-sines stimulus that minimized the effects of predictive visual tracking; differences of gain values between near- and mirror-viewing conditions were similar to those during rotation at 2 Hz. We conclude that, in these experiments, target proximity and vergence angle were not the key determinants of gain of the visuo-vestibular response during head rotation while viewing a near target but that contextual cues from motion vision were more important in generating the appropriate response.
GABACρ1Subunits Form Functional Receptors But Not Functional Synapses in Hippocampal Neurons
Authors: Cheng Qing , Burkat Paul M. , Kulli John C. , Yang Jay
Published: December 2017

The ability to control the physiological and pharmacological properties of synaptic receptors is a powerful tool for studying neuronal function and may be of therapeutic utility. We designed a recombinant adenovirus to deliver either a GABACreceptor ρ1subunit or a mutant GABAAreceptor β2subunit lacking picrotoxin sensitivity [β2(mut)] to hippocampal neurons. A green fluorescent protein (GFP) reporter molecule was simultaneously expressed. Whole cell patch-clamp recordings demonstrated somatic expression of both bicuculline-resistant GABACreceptor-mediated and picrotoxin-resistant GABAAreceptor-mediated GABA-evoked currents in ρ1- and β2(mut)-transduced hippocampal neurons, respectively. GABAergic miniature inhibitory postsynaptic currents (mIPSCs) recorded in the presence of 6-cyano-7-nitroquinoxalene-2,3-dione, Mg2+, and TTX revealed synaptic events with monoexponential activation and biexponential decay phases. Despite the robust expression of somatic GABACreceptors in ρ1-neurons, no bicuculline-resistant mIPSCs were observed. This suggested either a kinetic mismatch between the relatively brief presynaptic GABA release and slow-activating ρ1receptors or failure of the ρ1subunit to target properly to the subsynaptic membrane. Addition of ruthenium red, a presynaptic release enhancer, failed to unmask GABACreceptor-mediated mIPSCs. Short pulse (2 ms) application of 1 mM GABA to excised outside-out patches from ρ1neurons proved that a brief GABA transient is sufficient to activate ρ1receptors. The simulated-IPSC experiment strongly suggests that if postsynaptic GABACreceptors were present, bicuculline-resistant mIPSCs would have been observed. In contrast, in β2(mut)-transduced neurons, picrotoxin-resistant mIPSCs were observed; they exhibited a smaller peak amplitude and faster decay compared with control. Confocal imaging of transduced neurons revealed ρ1immunofluorescence restricted to the soma, whereas punctate β2(mut) immunofluorescence was seen throughout the neuron, including the dendrites. Together, the electrophysiological and imaging data show that despite robust somatic expression of the ρ1subunit, the GABACreceptor fails to be delivered to the subsynaptic target. On the other hand, the successful incorporation of β2(mut) subunits into subsynaptic GABAAreceptors demonstrates that viral transduction is a powerful method for altering the physiological properties of synapses.
Differential Representation of Species-Specific Primate Vocalizations in the Auditory Cortices of Marmoset and Cat
Authors: Wang Xiaoqin , Kadia Siddhartha C.
Published: December 2017

A number of studies in various species have demonstrated that natural vocalizations generally produce stronger neural responses than do their time-reversed versions. The majority of neurons in the primary auditory cortex (A1) of marmoset monkeys responds more strongly to natural marmoset vocalizations than to the time-reversed vocalizations. However, it was unclear whether such differences in neural responses were simply due to the difference between the acoustic structures of natural and time-reversed vocalizations or whether they also resulted from the difference in behavioral relevance of both types of the stimuli. To address this issue, we have compared neural responses to natural and time-reversed marmoset twitter calls in A1 of cats with those obtained from A1 of marmosets using identical stimuli. It was found that the preference for natural marmoset twitter calls demonstrated in marmoset A1 was absent in cat A1. While both cortices responded approximately equally to time-reversed twitter calls, marmoset A1 responded much more strongly to natural twitter calls than did cat A1. This differential representation of marmoset vocalizations in two cortices suggests that experience-dependent and possibly species-specific mechanisms are involved in cortical processing of communication sounds.
Modification of Response Functions of Cat Visual Cortical Cells by Spatially Congruent Perturbing Stimuli
Authors: Kabara Joseph F. , Bonds A. B.
Published: December 2017

Responses of cat striate cortical cells to a drifting sinusoidal grating were modified by the superimposition of a second, perturbing grating (PG) that did not excite the cell when presented alone. One consequence of the presence of a PG was a shift in the tuning curves. The orientation tuning of all 41 cells exposed to a PG and the spatial frequency tuning of 83% of the 23 cells exposed to a PG showed statistically significant dislocations of both the response function peak and center of mass from their single grating values. As found in earlier reports, the presence of PGs suppressed responsiveness. However, reductions measured at the single grating optimum orientation or spatial frequency were on average 1.3 times greater than the suppression found at the peak of the response function modified by the presence of the PG. Much of the loss in response seen at the single grating optimum is thus a result of a shift in the tuning function rather than outright suppression. On average orientation shifts were repulsive and proportional (∼0.10 deg/deg) to the angle between the perturbing stimulus and the optimum single grating orientation. Shifts in the spatial frequency response function were both attractive and repulsive, resulting in an overall average of zero. For both simple and complex cells, PGs generally broadened orientation response function bandwidths. Similarly, complex cell spatial frequency response function bandwidths broadened. Simple cell spatial frequency response functions usually did not change, and those that did broadened only 4% on average. These data support the hypothesis that additional sinusoidal components in compound stimuli retune cells' response functions for orientation and spatial frequency.
Quantitative Modeling of Perception and Production of Time Intervals
Authors: Migliore M. , Messineo L. , Cardaci M. , Ayala G. F.
Published: December 2017

The accurate perception/production of durations in the seconds and minutes range is important in a number of everyday activities, but the lack of direct experimental evidence on the neural circuits that could be involved has precluded the detailed elucidation of the underlying physiological mechanisms. We show, using a basic biophysical model of a timekeeping system and experimental data on time intervals produced or estimated under different conditions, that experimental values, variability, and distributions can be quantitatively explained in terms of a background synaptic activity such as that generated by attention. The model provides a plausible neural substrate for encoding time intervals, and the findings suggest how it may interplay at the single neuron level with the attentional system, to elaborate a subjective representation of the elapsing time.
A Central Pattern-Generating Network Contributes to “Reflex-Reversal”–Like Leg Motoneuron Activity in the Locust
Authors: Knop Gabriel , Denzer Lars , Büschges Ansgar
Published: December 2017

We introduce a new rhythmic preparation of the locust mesothoracic segment that exhibits long-lasting rhythmicity without pharmacological treatment. In most experiments, isolation of the locust mesothoracic ganglion from the anterior and posterior ganglia causes episodes of patterned activity to be generated in leg motoneurons that supply the femur-tibia (FT) joint. Flexor and extensor tibiae motoneuron pools exhibit alternating bursts of activity mostly composed of doublets and triplets of bursts. Motor activity during these episodes appears to be centrally generated because it persisted after complete deafferentation in 37% of the preparations; however, proprioceptive signals from the middle leg strongly influenced the patterning of motoneuron activity. Mimicking FT joint flexion by elongating the femoral chordotonal organ during an extensor burst terminates extensor activity and initiates flexor activity. The reverse is true for a mimicked extension during a flexor burst. This motor activity represents a reflex reversal that is typically observed in the locomotor state of the stick insect walking system. Our results provide evidence that this “reversed” reflex is caused by the action of central pattern-generating networks.
Strychnine Alters Response Properties of Trigeminal Nociceptive Neurons in the Rat
Authors: Ressot Catherine , Collado Valerie , Molat Jean-Louis , Dallel Radhouane
Published: December 2017

The purpose of this study was to examine the role of glycine in sensory processes in the spinal trigeminal nucleus oralis (Sp5O). We evaluated the effect of intravenous administration of strychnine, a glycine receptor antagonist, on the responses of Sp5O convergent neurons evoked by innocuous peripheral electrical and mechanical stimuli in halothane-anesthetized rats. Strychnine significantly increased the Aβ-fiber–evoked activities of Sp5O neurons to electrical stimulation in a dose-dependent (0.2–0.8 mg/kg) fashion. The response to air-jet stimulation was also significantly enhanced at the highest dose of strychnine. These findings indicate that glycinergic neurons participate in the control of the flow of information conveyed to Sp5O nociceptive neurons by myelinated low-threshold mechanoreceptive afferents. Thus, alteration of trigeminal glycinergic modulation may contribute to the dynamic mechanical allodynia that occurs in trigeminal neuropathies.
Noradrenaline Excites and Inhibits GABAergic Transmission in Parvocellular Neurons of Rat Hypothalamic Paraventricular Nucleus
Authors: Han Seong Kyu , Chong Wonee , Li Long Hua , Lee In Se , Murase Kazuyuki , Ryu Pan Dong
Published: December 2017

Noradrenaline (NA) is a major neurotransmitter that regulates many neuroendocrine and sympathetic autonomic functions of the hypothalamic paraventricular nucleus (PVN). Previously NA has been shown to increase the frequency of excitatory synaptic activity of parvocellular neurons within the PVN, but little is known about its effects on inhibitory synaptic activity. In this work, we studied the effects of NA (1–100 μM) on the spontaneous inhibitory synaptic currents (sIPSC) of type II PVN neurons in brain slices of the rat using the whole cell patch-clamp technique. Spontaneous IPSCs were observed from most type II neurons ( n = 121) identified by their anatomical location within the PVN and their electrophysiological properties. Bath application of NA (100 μM) increased sIPSC frequency by 256% in 59% of the neurons. This effect was blocked by prazosin (2–20 μM), the α1-adrenoceptor antagonist and mimicked by phenylephrine (10–100 μM), the α1-adrenoceptor agonist. However, in 33% of the neurons, NA decreased sIPSC frequency by 54%, and this effect was blocked by yohimbine (2–20 μM), the α2-adrenoceptor antagonist and mimicked by clonidine (50 μM), the α2-adrenoceptor agonist. The Na+ channel blocker, tetrodotoxin (0.1 μM) blocked the α1-adrenoceptor–mediated effect, but not the α2-adreonoceptor–mediated one. Both of the stimulatory and inhibitory effects of NA on sIPSC frequency were observed in individual neurons when tested with NA alone, or both phenylephrine and clonidine. Furthermore, in most neurons that showed the stimulatory effects, the inhibitory effects of NA were unmasked after blocking the stimulatory effects by prazosin or tetrodotoxin. These data indicate that tonic GABAergic inputs to the majority of type II PVN neurons are under a dual noradrenergic modulation, the increase in sIPSC frequency via somatic or dendritic α1-adrenoceptors and the decrease in sIPSC frequency via axonal terminal α2-adrenoceptors on the presynaptic GABAergic neurons.
Long-Term Alteration of S-Type Potassium Current and Passive Membrane Properties inAplysiaSensory Neurons Following Axotomy
Authors: Ungless Mark A. , Gasull Xavier , Walters Edgar T.
Published: December 2017

In many neurons, axotomy triggers long-lasting alterations in excitability as well as regenerative growth. We have investigated mechanisms contributing to the expression of axotomy-induced, long-term hyperexcitability (LTH) of mechanosensory neurons in Aplysia californica. Electrophysiological tests were applied to pleural sensory neurons 5–10 days after unilateral crush of pedal nerves. Two-electrode current-clamp experiments revealed that compared with uninjured sensory neurons on the contralateral side of the body, axotomized sensory neurons consistently displayed alterations of passive membrane properties: notably, increases in input resistance ( Rin), membrane time constant (τ), and apparent input capacitance. In some cells, axotomy also depolarized the resting membrane potential (RMP). Axotomized sensory neurons showed a lower incidence of voltage relaxation (“sag”) during prolonged hyperpolarizing pulses and greater depolarizations during long (2 s) but not brief (20 ms) pulses. In addition to a reduction in spike accommodation, axotomized sensory neurons displayed a dramatic decrease in current (rheobase) required to reach spike threshold during long depolarizations. The increase in τ was associated with prolongation of responses to brief current pulses and with a large increase in the latency to spike at rheobase. Two-electrode voltage-clamp revealed an axotomy-induced decrease in a current with two components: a leakage current component and a slowly activating, noninactivating outward current component. Neither component was blocked by agents known to block other K+currents in these neurons. In contrast to the instantaneous leakage current seen with hyperpolarizing and depolarizing steps, the late component of the axotomy-sensitive outward current showed a relatively steep voltage dependence with pulses to Vm> −40 mV. These features match those of the S-type (“serotonin-sensitive”) K+current, IK,S. The close resemblance of IK,Sto a background current mediated by TREK-1 (KCNK2) channels in mammals, raises interesting questions about alterations of this family of channels during axotomy-induced LTH in both Aplysia and mammals. The increase in apparent Cinmay be a consequence of the extensive sprouting that has been observed in axotomized sensory neurons near their somata, and the decrease in IK,Sprobably helps to compensate for the decrease in excitability that would otherwise occur as new growth causes both cell volume and Cinto increase. In peripheral regions of the sensory neuron, a decrease in IK,Smight enhance the safety factor for conduction across regenerating segments that are highly susceptible to conduction block.
Intracellularly Labeled Fusiform Cells in Dorsal Cochlear Nucleus of the Gerbil. I. Physiological Response Properties
Authors: Hancock Kenneth E. , Voigt Herbert F.
Published: December 2017

Fusiform cells in the dorsal cochlear nucleus (DCN) of barbiturate-anesthetized Mongolian gerbils were characterized physiologically and labeled with neurobiotin. This report is based on 17 fusiform cells for which there was reasonable confidence in the association between physiological data and recovered anatomy. The qualitative morphology of these cells was no different from that reported in previous studies. The acoustic response properties were generally consistent with those described in the barbiturate-anesthetized cat. Most responses were of the pauser or buildup type, but a dependence on stimulus frequency and intensity was observed. Stimulus-evoked sustained depolarizations and large, long-lasting afterhyperpolarizations were common membrane potential features. The cells in this study showed a greater tendency to discharge regularly than did those of the cat, likely as a result of the longer interstimulus interval used. Barbiturate anesthesia appears to mask an interspecies difference in DCN physiology that is apparent in unanesthetized, decerebrate preparations. The response of these fusiform cells to a depolarizing current pulse could be altered by the presence of a hyperpolarizing prepulse. Buildup, pauser, and chopper patterns could each be created using appropriate combinations of hyperpolarizing and depolarizing pulse amplitudes. Thus the adult gerbil appears to express the inactivating potassium conductance previously shown to affect fusiform cell firing patterns in vitro. The results further demonstrate that the effects of these potassium currents are readily observed in vivo. Finally, the fusiform cells in this study were quite variable with respect to a number of response properties, including the resting potential, input resistance, spontaneous activity, relative noise index, normalized tone slope, and regularity histogram shape. This diversity likely results from cell-to-cell variations in the balance of activity within the relatively complex network to which the fusiform cells belong, although effects of impalement may contribute to the extent of the diversity.
Activity-Dependent Expression of Simultaneous Glutamatergic and GABAergic Neurotransmission From the Mossy Fibers In Vitro
Authors: Gutiérrez Rafael
Published: December 2017

GABAergic transmission in the mossy fiber (MF) projection of the hippocampus is not normally detected in the rat. However, seizures induce simultaneous glutamatergic and GABAergic transmission in this projection, which coincides with an overexpression of GAD67 and vesicular GABA transporter (VGAT) mRNA in the dentate gyrus (DG) and MF. To test whether this plastic change could be induced in an activity-dependent fashion in the absence of seizures, I recorded intracellularly from slices/cells that served as their own control, before and after direct or synaptic kindling of the DG in vitro. As expected, synaptic responses of CA3 pyramidal cells to test pulse DG stimulation were blocked by perfusion of N-methyl-d-aspartate (NMDA) and non-NMDA receptors' antagonists. However, after kindling the perforant path (3 1-s trains of 0.1-ms pulses at 100 Hz, 1 min appart from each other every 15 min for 3 h), which potentiated synaptic responses without inducing epileptiform activity, the perfusion of glutamatergic antagonists blocked the excitatory synaptic potential and isolated a fast bicuculline-sensitive inhibitory synaptic potential. Immunohistochemical experiments confirmed the overexpression of GAD67 in the kindled slices. If kindling stimulation was provided just for 1 h or if it was completed in the presence of the protein synthesis inhibitor, cycloheximide, the expression of the GABAergic potential was prevented. Alternatively, when control synaptic responses of a given cell were first blocked, the direct kindling stimulation over the same site during perfusion of glutamatergic antagonists resulted in the induction of fast GABAergic potentials after 16.6 ± 0.9 kindling trials. Furthermore, a high spacial specificity of this phenomenon was evidenced by recording synaptic responses of a given pyramidal cell to two different MF inputs. After blockade of all synaptic responses with the perfusion of glutamatergic antagonists, one of the inputs was kindled, while synaptic responses between the kindling trials were monitored by applying test pulse stimulation to both inputs. After 17 ± 1 trials, test pulse stimulation provided over the kindled site evoked GABAergic potentials, whereas test pulse stimulation delivered to the alternative nonkindled parallel MF input remained ineffective. The DG-evoked GABAergic responses were inhibited by the activation of GABABR and mGluR, whereby activation of group III mGluR with l-2-amino-4-phosphonobutyric acid (l-AP4) was significantly more effective than the activation of group II mGluR with DCG-IV. These data demonstrate that GABAergic transmission from the MF projection has distinctive features in the adult rat, and that its induction is dependent on protein synthesis responding in an activity-dependent fashion.