bluuebunny/crossref_metadata_2025 huggingface dataset:
Neural Responses to Overlapping FM Sounds in the Inferior Colliculus of Echolocating Bats
Authors: Sanderson Mark I. , Simmons James A.
Published: December 2017

The big brown bat, Eptesicus fuscus, navigates and hunts prey with echolocation, a modality that uses the temporal and spectral differences between vocalizations and echoes from objects to build spatial images. Closely spaced surfaces (“glints”) return overlapping echoes if two echoes return within the integration time of the cochlea (∼300–400 μs). The overlap results in spectral interference that provides information about target structure or texture. Previous studies have shown that two acoustic events separated in time by less than ∼500 μs evoke only a single response from neural elements in the auditory brain stem. How does the auditory system encode multiple echoes in time when only a single response is available? We presented paired FM stimuli with delay separations from 0 to 24 μs to big brown bats and recorded local field potentials (LFPs) and single-unit responses from the inferior colliculus (IC). These stimuli have one or two interference notches positioned in their spectrum as a function of two-glint separation. For the majority of single units, response counts decreased for two-glint separations when the resulting FM signal had a spectral notch positioned at the cell's best frequency (BF). The smallest two-glint separation that reliably evoked a decrease in spike count was 6 μs. In addition, first-spike latency increased for two-glint stimuli with notches positioned nearby BF. The N4 potential of averaged LFPs showed a decrease in amplitude for two-glint separations that had a spectral notch near the BF of the recording site. Derived LFPs were computed by subtracting a common-mode signal from each LFP evoked by the two-glint FM stimuli. The derived LFP records show clear changes in both the amplitude and latency as a function of two-glint separation. These observations in relation with the single-unit data suggest that both response amplitude and latency can carry information about two-glint separation in the auditory system of E. fuscus.
Reorganization of the Frequency Map of the Auditory Cortex Evoked by Cortical Electrical Stimulation in the Big Brown Bat
Authors: Chowdhury Syed A. , Suga Nobuo
Published: December 2017

In a search phase of echolocation, big brown bats, Eptesicus fuscus, emit biosonar pulses at a rate of 10/s and listen to echoes. When a short acoustic stimulus was repetitively delivered at this rate, the reorganization of the frequency map of the primary auditory cortex took place at and around the neurons tuned to the frequency of the acoustic stimulus. Such reorganization became larger when the acoustic stimulus was paired with electrical stimulation of the cortical neurons tuned to the frequency of the acoustic stimulus. This reorganization was mainly due to the decrease in the best frequencies of the neurons that had best frequencies slightly higher than those of the electrically stimulated cortical neurons or the frequency of the acoustic stimulus. Neurons with best frequencies slightly lower than those of the acoustically and/or electrically stimulated neurons slightly increased their best frequencies. These changes resulted in the over-representation of repetitively delivered acoustic stimulus. Because the over-representation resulted in under-representation of other frequencies, the changes increased the contrast of the neural representation of the acoustic stimulus. Best frequency shifts for over-representation were associated with sharpening of frequency-tuning curves of 25% of the neurons studied. Because of the increases in both the contrast of neural representation and the sharpness of tuning, the over-representation of the acoustic stimulus is accompanied with an improvement of analysis of the acoustic stimulus.
Older Adults Use a Unique Strategy to Lift Inertial Loads With the Elbow Flexor Muscles
Authors: Graves Andrew E. , Kornatz Kurt W. , Enoka Roger M.
Published: December 2017

The purpose of this study was to determine the effect of age on the ability to exert steady forces and to perform steady flexion movements with the muscles that cross the elbow joint. An isometric task required subjects to exert a steady force to match a target force that was displayed on a monitor. An anisometric task required subjects to raise and lower inertial loads so that the angular displacement around the elbow joint matched a template displayed on a monitor. Steadiness was measured as the coefficient of variation of force and as the normalized standard deviation of wrist acceleration. For the isometric task, steadiness as a function of target force decreased similarly for old adults and young adults. For the anisometric task, steadiness increased as a function of the inertial load and there were significant differences caused by age. Old adults were less steady than young adults during both shortening and lengthening contractions with the lightest loads. Furthermore, old adults were least steady when performing lengthening contractions. These behaviors appear to be associated with the patterns of muscle activation. These results suggest that different neural strategies are used to control isometric and anisometric contractions performed with the elbow flexor muscles and that these strategies do not change in parallel with advancing age.
Permanent Reduction of Seizure Threshold in Post-Ischemic CA3 Pyramidal Neurons
Authors: Congar Patrice , Gaïarsa Jean-Luc , Popovici Théodora , Ben-Ari Yezekiel , Crépel Valérie
Published: December 2017

The effects of ischemia were examined on CA3 pyramidal neurons recorded in hippocampal slices 2–4 mo after a global forebrain insult. With intracellular recordings, CA3 post-ischemic neurons had a more depolarized resting membrane potential but no change of the input resistance, spike threshold and amplitude, fast and slow afterhyperpolarization (AHP) or ADP, and firing properties in response to depolarizing pulses. With both field and whole-cell recordings, synaptic responses were similar in control and post-ischemic neurons. Although there were no spontaneous network-driven discharges, the post-ischemic synaptic network had a smaller threshold to generate evoked and spontaneous synchronized burst discharges. Thus lower concentrations of convulsive agents (kainate, high K+) triggered all-or-none network-driven synaptic events in post-ischemic neurons more readily than in control ones. Also, paired-pulse protocol generates, in post-ischemics but not controls, synchronized field burst discharges when interpulse intervals ranged from 60 to 100 ms. In conclusion, 2–4 mo after the insult, the post-ischemic CA3 pyramidal cells are permanently depolarized and have a reduced threshold to generate synchronized bursts. This may explain some neuropathological and behavioral consequences of ischemia as epileptic syndromes observed several months to several years after the ischemic insult.
Optimal Sizes of Dendritic and Axonal Arbors in a Topographic Projection
Authors: Chklovskii Dmitri B.
Published: December 2017

I consider a topographic projection between two neuronal layers with different densities of neurons. Given the number of output neurons connected to each input neuron (divergence) and the number of input neurons synapsing on each output neuron (convergence), I determine the widths of axonal and dendritic arbors which minimize the total volume of axons and dendrites. Analytical results for one-dimensional and two-dimensional projections can be summarized qualitatively in the following rule: neurons of the sparser layer should have arbors wider than those of the denser layer. This agrees with the anatomic data for retinal, cerebellar, olfactory bulb, and neocortical neurons the morphology and connectivity of which are known. The rule may be used to infer connectivity of neurons from their morphology.
Size of CA1-Evoked Synaptic Potentials Is Related to Theta Rhythm Phase in Rat Hippocampus
Authors: Wyble Bradley P. , Linster Christiane , Hasselmo Michael E.
Published: December 2017

Cholinergic and GABAergic neurons projecting to the hippocampus fire with specific phase relations to theta rhythm oscillations in the electroencephalogram (EEG). To determine if this phasic input has an impact on synaptic transmission within the hippocampus, we recorded evoked population excitatory postsynaptic potential (EPSPs) during different phases of theta rhythm by using techniques similar to those described in Rudell and Fox. Synaptic potentials elicited by stimulation of region CA3 of the contralateral hippocampus were recorded in region CA1 and CA3. In these experiments, the initial slope of evoked potentials showed a change in magnitude during different phases of the theta rhythm recorded in the dentate fissure, with individual trials showing an average of 9.5% change in slope of potentials, and the average across all experiments showing a change of 7.8%. Evoked potentials were maximal 18° after the positive peak of the dentate fissure theta EEG. These potentials were also smaller by 18.2% during theta as opposed to non-theta states. Phasic changes in modulation of synaptic transmission could contribute to phase precession of hippocampal place cells and could enhance storage of new sequences of activity as demonstrated by computational models.
Brain Nitric Oxide Changes After Controlled Cortical Impact Injury in Rats
Authors: Cherian Leela , Goodman J. Clay , Robertson Claudia S.
Published: December 2017

Nitric oxide (NO) and the NO end products, nitrate and nitrite, were measured at the impact site after a 5-m/s, 3-mm deformation controlled cortical impact injury in rats. Immediately after the impact injury and the NO and microdialysis probes could be replaced, there was an increase from baseline in NO concentration of 83 ± 16 (SE) nM, compared with 0.5 ± 4 nM in the sham injured animals ( P < 0.001). This marked increase in NO occurred at the time of the initial rise in blood pressure (BP) and intracranial pressure (ICP) in response to the injury. After the initial increase in BP and ICP, the BP decreased and stabilized at a value which was ∼20 mmHg below the preinjury values, and ICP plateaued at an average value of 20 mmHg, compared with 8 mmHg in the sham-injured animals. This provided an average cerebral perfusion pressure of 40–50 mmHg, compared with 65–75 mmHg for the sham-injured animals. These values were relatively constant for the remainder of the 3-h monitoring period. The NO values also stabilized during this time period. By 1 h after the impact injury the NO concentration measured directly using the NO electrode had decreased from baseline values by an average value of 25 ± 6 nM. NO concentration remained significantly lower than baseline values throughout the remainder of the 3-h monitoring period. The concentration of nitrate/nitrite in the dialysate fluid also decreased by an average value of 341 ± 283 nM 20–40 min after the injury. Dialysate nitrite/nitrate concentrations remained less than the preinjury baseline values throughout the remainder of the 3-h monitoring period. Preinjury treatment with l-nitro-arginine methyl ester (l-NAME) blunted the injury-induced increase in NO and resulted in more severe immediate intracranial hypertension and more severe systemic hypotension at one hour after injury. Mortality was also 67% with l-NAME pretreatment, compared with 1% in untreated animals.
Differential Effects of μ-, δ-, and κ-Opioid Receptor Agonists on Mechanosensitive Gastric Vagal Afferent Fibers in the Rat
Authors: Ozaki Noriyuki , Sengupta J. N. , Gebhart G. F.
Published: December 2017

Single-fiber recordings were made from the decentralized right cervical vagus nerve (hyponodosal) of the rat. A total of 56 afferent fibers that responded to gastric distension (GD) were studied: 6 fibers were stimulated by phasic balloon GD, 50 by fluid GD. All fibers gave increasing responses to increasing pressures of GD (5–60 mmHg). The effects of μ-opioid (morphine), δ-opioid (SNC80), and κ-opioid (EMD61,753, U62,066) receptor agonists were tested on responses of afferent fibers to GD. Morphine, administered systemically over a broad dose range (10 μg to 31 mg/kg, cumulative), had no effect on either resting activity or responses of vagal afferent fibers to GD. Similarly, the δ-opioid receptor agonist SNC80 (0.05–3.2 mg/kg) did not affect resting activity or responses to GD. In contrast, cumulative intra-arterial doses of the κ-opioid receptor agonist EMD61,753 or U62,066 dose dependently attenuated afferent fiber responses to GD. Doses producing inhibition to 50% of the control response to GD of EMD61,753 (8.0 mg/kg) and U62,066 (8.8 mg/kg) did not differ. The effect of U62,066 was moderately attenuated by a nonselective dose (4 mg/kg) of naloxone hydrochloride; the κ-opioid receptor-selective antagonist nor-BNI (20 mg/kg) was ineffective. These results demonstrate that κ-, but not μ- or δ-opioid receptor agonists modulate visceral sensation conveyed by vagal afferent fibers innervating the stomach. Given that κ-opioid receptor agonists effects were only modestly antagonized by naloxone and not at all by nor-BNI, the results point to a novel site of action.
Voltage-Gated Calcium Currents in Axotomized Adult Rat Cutaneous Afferent Neurons
Authors: Baccei Mark L. , Kocsis Jeffery D.
Published: December 2017

The effect of sciatic nerve injury on the somatic expression of voltage-gated calcium currents in adult rat cutaneous afferent dorsal root ganglion (DRG) neurons identified via retrograde Fluoro-gold labeling was studied using whole cell patch-clamp techniques. Two weeks after a unilateral ligation and transection of the sciatic nerve, the L4–L5DRG were dissociated and barium currents were recorded from cells 3–10 h later. Cutaneous afferents (35–50 μm diam) were classified as type 1 (possessing only high-voltage–activated currents; HVA) or type 2 (having both high- and low-voltage–activated currents). Axotomy did not change the percentage of neurons exhibiting a type 2 phenotype or the properties of low-threshold T-type current found in type 2 neurons. However, in type 1 neurons the peak density of HVA current available at a holding potential of −60 mV was reduced in axotomized neurons (83.9 ± 5.6 pA/pF, n = 53) as compared with control cells (108.7 ± 6.9 pA/pF, n = 58, P < 0.01, unpaired t-test). A similar reduction was observed at more negative holding potentials, suggesting differences in steady-state inactivation are not responsible for the effect. Separation of the type 1 cells into different size classes indicates that the reduction in voltage-gated barium current occurs selectively in the larger (capacitance >80 pF) cutaneous afferents (control: 112.4 ± 10.6 pA/pF, n = 30; ligated: 72.6 ± 5.0 pA/pF, n = 36; P < 0.001); no change was observed in cells with capacitances of 45–80 pF. Isolation of the N- and P\Q-type components of the HVA current in the large neurons using ω-conotoxin GVIA and ω-agatoxin TK suggests a selective reduction in N-type barium current after nerve injury, as the density of ω-CgTx GVIA-sensitive current decreased from 56.9 ± 6.6 pA/pF in control cells ( n = 13) to 31.3 ± 4.6 pA/pF in the ligated group ( n = 12; P < 0.005). The HVA barium current of large cutaneous afferents also demonstrates a depolarizing shift in the voltage dependence of inactivation after axotomy. Injured type 1 cells exhibited faster inactivation kinetics than control neurons, although the rate of recovery from inactivation was similar in the two groups. The present results indicate that nerve injury leads to a reorganization of the HVA calcium current properties in a subset of cutaneous afferent neurons.
Selectivity for the Shape, Size, and Orientation of Objects for Grasping in Neurons of Monkey Parietal Area AIP
Authors: Murata Akira , Gallese Vittorio , Luppino Giuseppe , Kaseda Masakazu , Sakata Hideo
Published: December 2017

In this study, we mainly investigated the visual selectivity of hand-manipulation-related neurons in the anterior intraparietal area (area AIP) while the animal was grasping or fixating on three-dimensional (3D) objects of different geometric shapes, sizes, and orientations. We studied the activity of 132 task-related neurons during the hand-manipulation tasks in the light and in the dark, as well as during object fixation. Seventy-seven percent (101/132) of the hand-manipulation-related neurons were visually responsive, showing either lesser activity during manipulation in the dark than during that in the light (visual-motor neurons) or no activation in the dark (visual-dominant neurons). Of these visually responsive neurons, more than half ( n = 66) responded during the object-fixation task (object-type). Among these, 55 were tested for their shape selectivity during the object-fixation task, and many ( n = 25) were highly selective, preferring one particular shape of the six different shapes presented (ring, cube, cylinder, cone, sphere, and square plate). For 28 moderately selective object-type neurons, we performed multidimensional scaling (MDS) to examine how the neurons encode the similarity of objects. The results suggest that some moderately selective neurons responded preferentially to common geometric features shared by similar objects (flat, round, elongated, etc.). Moderately selective nonobject-type visually responsive neurons, which did not respond during object fixation, were found by MDS to be more closely related to the handgrip than to the object shape. We found a similar selectivity for handgrip in motor-dominant neurons that did not show any visual response. With regard to the size of the objects, 16 of 26 object-type neurons tested were selective for both size and shape, whereas 9 object-type neurons were selective for shape but not for size. Seven of 12 nonobject-type and all (8/8) of the motor-dominant neurons examined were selective for size, and almost all of them were also selective for objects. Many hand-manipulation-related neurons that preferred the plate and/or ring were selective for the orientation of the objects (17/20). These results suggest that the visual responses of object-type neurons represent the shape, size, and/or orientation of 3D objects, whereas those of the nonobject-type neurons probably represent the shape of the handgrip, grip size, or hand-orientation. The activity of motor-dominant neurons was also, in part, likely to represent these parameters of hand movement. This suggests that the dorsal visual pathway is concerned with the aspect of form, orientation, and/or size perception that is relevant for the visual control of movements.
Dynorphin A Elicits an Increase in Intracellular Calcium in Cultured Neurons Via a Non-Opioid, Non-NMDA Mechanism
Authors: Tang Qingbo , Lynch Ronald M. , Porreca Frank , Lai Josephine
Published: December 2017

The opioid peptide dynorphin A is known to elicit a number of pathological effects that may result from neuronal excitotoxicity. An up-regulation of this peptide has also been causally related to the dysesthesia associated with inflammation and nerve injury. These effects of dynorphin A are not mediated through opioid receptor activation but can be effectively blocked by pretreatment with N-methyl-d-aspartate (NMDA) receptor antagonists, thus implicating the excitatory amino acid system as a mediator of the actions of dynorphin A and/or its fragments. A direct interaction between dynorphin A and the NMDA receptors has been well established; however the physiological relevance of this interaction remains equivocal. This study examined whether dynorphin A elicits a neuronal excitatory effect that may underlie its activation of the NMDA receptors. Calcium imaging of individual cultured cortical neurons showed that the nonopioid peptide dynorphin A(2-17) induced a time- and dose-dependent increase in intracellular calcium. This excitatory effect of dynorphin A(2-17) was insensitive to (+)-5-methyl-10,11-dihydro-5 H-dibenzo[ a,d]-cyclohepten-5,10-imine (MK-801) pretreatment in NMDA-responsive cells. Thus dynorphin A stimulates neuronal cells via a nonopioid, non-NMDA mechanism. This excitatory action of dynorphin A could modulate NMDA receptor activity in vivo by enhancing excitatory neurotransmitter release or by potentiating NMDA receptor function in a calcium-dependent manner. Further characterization of this novel site of action of dynorphin A may provide new insight into the underlying mechanisms of dynorphin excitotoxicity and its pathological role in neuropathy.
Membrane Properties of Chick Semicircular Canal Hair Cells In Situ During Embryonic Development
Authors: Masetto S. , Perin P. , Malusà A. , Zucca G. , Valli P.
Published: December 2017

The electrophysiological properties of developing vestibular hair cells have been investigated in a chick crista slice preparation, from embryonic day 10 ( E10) to E21 (when hatching would occur). Patch-clamp whole-cell experiments showed that different types of ion channels are sequentially expressed during development. An inward Ca2+ current and a slow outward rectifying K+current ( I K(V)) are acquired first, at or before E10, followed by a rapid transient K+current ( I K(A)) at E12, and by a small Ca-dependent K+ current ( I KCa) at E14. Hair cell maturation then proceeds with the expression of hyperpolarization-activated currents: a slow I h appears first, around E16, followed by the fast inward rectifier I K1around E19. From the time of its first appearance, I K(A) is preferentially expressed in peripheral ( zone 1) hair cells, whereas inward rectifying currents are preferentially expressed in intermediate ( zone 2) and central ( zone 3) hair cells. Each conductance conferred distinctive properties on hair cell voltage response. Starting from E15, some hair cells, preferentially located at the intermediate region, showed the amphora shape typical of type I hair cells. From E17 (a time when the afferent calyx is completed) these cells expressed I K, L, the signature current of mature type I hair cells. Close to hatching, hair cell complements and regional organization of ion currents appeared similar to those reported for the mature avian crista. By the progressive acquisition of different types of inward and outward rectifying currents, hair cell repolarization after both positive- and negative-current injections is greatly strengthened and speeded up.
Possible Involvement of Undissociated Acid Molecules in the Acid Response of the Chorda Tympani Nerve of the Rat
Authors: Ogiso Kazuma , Shimizu Yasutake , Watanabe Ken , Tonosaki Keiichi
Published: December 2017

To test whether undissociated acid is capable of exciting the chorda tympani nerves in rats, we have used buffered acid solutions as taste stimuli. These solutions were prepared by adding alkali to weak acids, such as acetic acid, so that the proportion of undissociated and dissociated acids was varied whereas keeping the total acid concentration constant. When acetic acid solutions, adjusted to wide ranges of pH by NaOH, were applied to the tongue, the response magnitude of the chorda tympani nerves was not varied systematically with pH changes. However, if the sodium effect was eliminated by amiloride or replacement of cation by potassium or Tris[hydroxymethyl]aminomethane; NH2C(CH2OH)3 (Tris-base), the chorda tympani response was reduced systematically as pH increased. Similar results were obtained with citric acid and ascorbic acid. This pH-dependent change in taste nerve response to acid cannot be solely attributed to the proton gradient because the response magnitude induced by hydrogen itself, which was estimated from responses to strong acids, was much smaller than that by equi-pH acetic acid (∼85%). Thus we cannot explain the pH-dependent responses of the chorda tympani nerves to weak acids unless effects of undissociated acid molecules are postulated. It is therefore concluded that undissociated acids in weak acid solutions can be a stimulant to taste receptor cells.
Could Different Directions of Infant Stepping Be Controlled by the Same Locomotor Central Pattern Generator?
Authors: Lamb Tania , Yang Jaynie F.
Published: December 2017

This study examined the idea of whether the same central pattern generator (CPG) for locomotion can control different directions of walking in humans. Fifty-two infants, aged 2–11 mo, were tested. Infants were supported to walk on a treadmill at a variety of speeds. If forward stepping was elicited, stepping in the other directions (primarily sideways and backward) was attempted. The orientation of the infant on the treadmill belt determined the direction of stepping. In some infants, we also attempted to obtain a smooth transition from one direction to another by gradually changing the orientation of the infant during a stepping sequence. Limb segment motion and surface electromyography from the muscles of the lower limb were recorded. Most infants who showed sustained forward walking also could walk in all other directions. Thirty-three of 34 infants tested could step sideways. The success of eliciting backward stepping was 69%. Most of the infants who did not meet our backward stepping criteria did, however, make stepping movements. The different directions of stepping had similar responses to changes in treadmill speed. The relationship between stance and swing phase durations and cycle duration were the same regardless of the direction of stepping across a range of speeds. Some differences were noted in the muscle activation patterns during different directions of walking. For example, the hamstrings were much more active during the swing phase of backward walking compared with forward walking. The quadriceps was more active in the trailing leg during sideways walking. In some infants, we were able to elicit stepping along a continuum of directions. We found no discrete differences in either the electromyographic patterns or the temporal parameters of stepping as the direction of stepping was gradually changed. The results support the idea that the same locomotor CPG controls different directions of stepping in human infants. The fact that most infants were able to step in all directions, the similarity in the response to speed changes, and the absence of any discrete changes as the direction of stepping was changed gradually are all consistent with this hypothesis.
On the Origin of the Soleus H-Reflex Modulation Pattern During Human Walking and Its Task-Dependent Differences
Authors: Schneider Cyril , Lavoie Brigitte A. , Capaday Charles
Published: December 2017

Recently, Brooke and colleagues have suggested “that the strong inhibition arising from passive movement about the knee and hip joints, lays down the base for the soleus H-reflex gain modulation seen during human gait.” In particular stretch-evoked afferent activity from the quadriceps muscle was emphasized as the most important source of movement-induced inhibition of the H-reflex. To test this hypothesis we examined the kinematics and electromyographic (EMG) activity of the leg during human walking and correlated these with the modulation pattern of the soleus H-reflex. To further test the possible contribution of stretch-evoked quadriceps afferent activity to the soleus H-reflex modulation pattern during walking different walking gaits were studied. In one condition subjects were asked to walk with their knee locked in full extension by a rigid knee brace. In a second condition subjects were asked to walk backwards. During normal walking, the soleus H-reflex modulation pattern is strongly correlated with the EMG events of the soleus and tibialis anterior (TA), but not with hip, knee, or ankle angular displacement or velocity. When subjects walked with the knee locked in full extension, the amplitude of the H-reflex, its modulation pattern, and the task-dependent changes of its amplitude were the same as during normal walking. During backward walking, the H-reflex increases in late swing before activity of the soleus has begun and while the knee is flexing, an observation that highlights central control of the H-reflex amplitude. The effects of imposed flexion of the knee in passive subjects were also reexamined. The knee flexion imposed by the experimenter followed the same trajectory as that which occurred during the swing phase of the subject's step cycle. It was found that imposed knee flexions elicited a burst of TA EMG activity with an average latency of 81.6 ms (SD = 21 ms) in six out of eight subjects. Inhibition of the H-reflex, when it occurred, was associated with the occurrence of this burst. When subjects voluntarily flexed their right knee from an initial quiet standing posture, the inhibition of the soleus H-reflex began before flexion of the knee or that of any other leg segment. Once again the onset of inhibition was closely associated with the onset of activity in the TA. In the discussion section the present observations are examined in light of the predictions made by the movement-induced inhibition hypothesis of Brooke et al. It will be concluded that none of the predictions of this hypothesis were corroborated by present tests done during human walking. In consequence, we suggest that the modulation pattern of the H-reflex observed during normal human walking is centrally determined, as are the task-dependent differences of its amplitude (e.g., standing versus the stance phase of human walking).
Contextual Modulation of Substantia Nigra Pars Reticulata Neurons
Authors: Handel Ari , Glimcher Paul W.
Published: December 2017

Neurons in the substantia nigra pars reticulata (SNr) are known to encode saccadic eye movements within some, but not all, behavioral contexts. However, the precise contextual factors that effect the modulations of nigral activity are still uncertain. To further examine the effect of behavioral context on the SNr, we recorded the activity of 72 neurons while monkeys made saccades during a delayed saccade task and during periods of free viewing. We quantified and compared the movement fields of each neuron for saccades made under three different conditions: 1) spontaneous saccades, which shifted gaze during periods of free viewing when no stimuli were presented and no reinforcements were delivered; 2) fixational saccades, which brought gaze into alignment with a fixation target at the start of a delayed saccade trial, were necessary for trial completion, but were not directly followed by reinforcement; and 3) terminal saccades, which brought gaze into alignment with a visual target at the end of a delayed saccade trial and were directly followed by reinforcement. For three of the four SNr neuron classes, saccade-related modulations were only present before terminal saccades. For the fourth class, discrete pausers, saccade-related modulations were substantially larger for terminal saccades than for fixational saccades, and modulations were absent for spontaneous saccades. These results and other recent work on the basal ganglia suggest that some saccade-related signals in the SNr may be influenced by the reinforcement associated with a particular saccadic eye movement.
Retroambiguus Projections to the Cutaneus Trunci Motoneurons May Form a Pathway in the Central Control of Mating
Authors: Gerrits Peter O. , Vodde Chris , Holstege Gert
Published: December 2017

Our laboratory has proposed that the nucleus retroambiguus (NRA) generates the specific motor performance displayed by female cats during mating and that it uses direct pathways to the motoneurons of the lower limb muscles involved in this activity. In the hamster a similar NRA-projection system could generate the typical female mating posture, which is characterized by lordosis of the back as well as elevation of the tail. The present study attempted to determine whether this elevation of the tail is also part of the NRA-mating control system. The basic assumption was that elevation of the tail is a function of the cutaneus trunci muscle (CTM), which was verified by bilateral tetanic stimulation of the lateral thoracic nerves innervating the CTM. It resulted in upward movement of the tail to a position similar to the tail-up position during the lordosis posture. Retrograde tracing results showed that CTM motoneurons are located in the ventral and ventrolateral part of the C7–C8 ventral horn, those innervating the tail region ventrolateral to those innervating the axillary region. Anterograde tracing studies showed that NRA fibers terminate bilaterally in both parts of the CTM motoneuronal cell groups. Electron microscopical studies revealed that labeled NRA terminals make monosynaptic contacts with retrogradely labeled dendrites of CTM motoneurons. Almost all of these terminal profiles had asymmetric synapses and contained spherical vesicles, which suggests an excitatory function. The observation that 15% of the labeled NRA terminals make more than one synaptic contact with a retrogradely labeled CTM motoneuronal dendrite within the same section indicates how powerful the NRA-CTM projection is. The results indicate that during mating the NRA not only could generate the lordosis posture but also the elevation of the tail.
Responses to Rare Visual Target and Distractor Stimuli Using Event-Related fMRI
Authors: Clark Vincent P. , Fannon Sean , Lai Song , Benson Randall , Bauer Lance
Published: December 2017

Previous studies have found that the P300 or P3 event-related potential (ERP) component is useful in the diagnosis and treatment of many disorders that influence CNS function. However, the anatomic locations of brain regions involved in this response are not precisely known. In the present event-related functional magnetic resonance imaging (fMRI) study, methods of stimulus presentation, data acquisition, and data analysis were optimized for the detection of brain activity in response to stimuli presented in the three-stimulus oddball task. This paradigm involves the interleaved, pseudorandom presentation of single block-letter target and distractor stimuli that previously were found to generate the P3b and P3a ERP subcomponents, respectively, and frequent standard stimuli. Target stimuli evoked fMRI signal increases in multiple brain regions including the thalamus, the bilateral cerebellum, and the occipital-temporal cortex as well as bilateral superior, medial, inferior frontal, inferior parietal, superior temporal, precentral, postcentral, cingulate, insular, left middle temporal, and right middle frontal gyri. Distractor stimuli evoked an fMRI signal change bilaterally in inferior anterior cingulate, medial frontal, inferior frontal, and right superior frontal gyri, with additional activity in bilateral inferior parietal lobules, lateral cerebellar hemispheres and vermis, and left fusiform, middle occipital, and superior temporal gyri. Significant variation in the amplitude and polarity of distractor-evoked activity was observed across stimulus repetitions. No overlap was observed between target- and distractor-evoked activity. These event-related fMRI results shed light on the anatomy of responses to target and distractor stimuli that have proven useful in many ERP studies of healthy and clinically impaired populations.
Plasticity in the Distribution of the Red Nucleus Output to Forearm Muscles After Unilateral Lesions of the Pyramidal Tract
Authors: Belhaj-Saïf Abderraouf , Cheney Paul D.
Published: December 2017

It has been hypothesized that the magnocellular red nucleus (RNm) contributes to compensation for motor impairments associated with lesions of the pyramidal tract. To test this hypothesis, we used stimulus triggered averaging (StTA) of electromyographic (EMG) activity to characterize changes in motor output from the red nucleus after lesions of the pyramidal tract. Three monkeys were trained to perform a reach and prehension task. EMG activity was recorded from 11 forearm muscles including one elbow, five wrist, and five digit muscles. Microstimulation (20 μA at 20 Hz) was delivered throughout the movement task to compute StTAs. Two monkeys served as controls. In a third monkey, 65% of the left pyramidal tract had been destroyed by an electrolytic lesion method five years before recording. The results demonstrate a clear pattern of postlesion reorganization in red nucleus–mediated output effects on forearm muscles. The normally prominent extensor preference in excitatory output from the RNm (92% in extensors) was greatly diminished in the lesioned monkey (59%). Similarly, suppression effects, which are normally much more prominent in flexor than in extensor muscles (90% in flexors), were also more evenly distributed after recovery from pyramidal tract lesions. Because of the limited excitatory output from the RNm to flexor muscles that normally exists, loss of corticospinal output would leave control of flexors particularly weak. The changes in RNm organization reported in this study would help restore function to flexor muscles. These results support the hypothesis that the RNm is capable of reorganization that contributes to the recovery of forelimb motor function after pyramidal tract lesions.
Control of the Wrist in Three-Joint Arm Movements to Multiple Directions in the Horizontal Plane
Authors: Koshland Gail F. , Galloway James C. , Nevoret-Bell Cedrine J.
Published: December 2017

In a reaching movement, the wrist joint is subject to inertial effects from proximal joint motion. However, precise control of the wrist is important for reaching accuracy. Studies of three-joint arm movements report that the wrist joint moves little during point-to-point reaches, but muscle activities and kinetics have not yet been described across a range of movement directions. We hypothesized that to minimize wrist motion, muscle torques at the wrist must perfectly counteract inertial effects arising from proximal joint motion. Subjects were given no instructions regarding joint movement and were observed to keep the wrist nearly motionless during center-out reaches to directions throughout the horizontal plane. Consistent with this, wrist muscle torques exactly mirrored interaction torques, in contrast to muscle torques at proximal joints. These findings suggest that in this reaching task the nervous system chooses to minimize wrist motion by anticipating dynamic inertial effects. The wrist muscle torques were associated with a direction-dependent choice of muscles, also characterized by initial reciprocal activation rather than initial coactivation to stiffen the wrist joint. In a second experiment, the same pattern of muscle acitivities persisted even after many trials reaching with the wrist joint immobilized. These results, combined with similar features at the three joints, such as cosine-like tuning of muscle torques and of muscle onsets across direction, suggest that the nervous system uses similar rules for muscles at each joint, as part of one plan for the arm during a point-to-point reach.
Light-Evoked Excitatory Synaptic Currents of X-Type Retinal Ganglion Cells
Authors: Cohen Ethan D.
Published: December 2017

The excitatory amino acid receptor (EAAR) types involved in the generation of light-evoked excitatory postsynaptic currents (EPSCs) were examined in X-type retinal ganglion cells. Using isolated and sliced preparations of cat and ferret retina, the light-evoked EPSCs of X cells were isolated by adding picrotoxin and strychnine to the bath to remove synaptic inhibition. N-methyl-d-aspartate (NMDA) receptors contribute significantly to the light-evoked EPSCs of on- andoff-X cells at many different holding potentials. An NMDA receptor contribution to the EPSCs was observable when retinal synaptic inhibition was either normally present or pharmacologically blocked. NMDA receptors formed 80% of the peak light-evoked EPSC at a holding potential of −40 mV; however, even at −80 mV, 20% of the light-evoked EPSC was NMDA-mediated. An α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptor–mediated component to the light-evoked EPSCs predominated at a holding potential of −80 mV. The light-evoked EPSC was blocked by the AMPA receptor-selective antagonist GYKI52466 (50–100 μM). The AMPA receptor–mediated EPSC component had a linear current-voltage relation. AMPA receptors form the main non-NMDA EAAR current on bothon- and off- X ganglion cell dendrites. When synaptic transmission was blocked by the addition of Cd2+to the Ringer, application of kainate directly to ganglion cells evoked excitatory currents that were strongly blocked by GYKI52466. Experiments using selective EAAR modulators showed the AMPA receptor–selective modulator cyclothiazide potentiated glutamate-evoked currents on X cells, while the kainate receptor–selective modulator concanavalin A (ConA) had no effect on kainate-evoked currents. Whereas the present study confirms the general notion that AMPA EAAR-mediated currents are transient and NMDA receptor–mediated currents are sustained, current-voltage relations of the light-evoked EPSC at different time points showed the contributions of these two receptor types significantly overlap. Both NMDA and AMPA EAARs can transmit transient and sustained visual signals in X ganglion cells, suggesting that much signal shaping occurs presynaptically in bipolar cells.
Anabolic Steroids Induce Region- and Subunit-Specific Rapid Modulation of GABAAReceptor-Mediated Currents in the Rat Forebrain
Authors: Jorge-Rivera Juan Carlos , McIntyre Kerry L. , Henderson Leslie P.
Published: December 2017

Anabolic-androgenic steroids (AAS) have become significant drugs of abuse in recent years with the highest increase reported in adolescent girls. In spite of the increased use of AAS, the CNS effects of these steroids are poorly understood. We report that in prepubertal female rats, three commonly abused AAS, 17α-methyltestosterone, stanozolol, and nandrolone, induced rapid and reversible modulation of GABAergic currents in neurons of two brain regions known to be critical for the expression of reproductive behaviors: the ventromedial nucleus of the hypothalamus (VMN) and the medial preoptic area (mPOA). All three AAS significantly enhanced peak synaptic current amplitudes and prolonged synaptic current decays in neurons of the VMN. Conversely all three AAS significantly diminished peak current amplitudes of synaptic currents from neurons of the mPOA. The endogenous neuroactive steroids, 3α-hydroxy-5α-pregnan-20-one and 5α-androstane-3α,17β-diol, potentiated currents in the VMN as did the AAS. In contrast to the negative modulation induced by AAS in the mPOA, the endogenous steroids potentiated responses in this region. To determine the concentration response relationships, modulation by the AAS, 17α-methyltestosterone (17α-meT), was assessed for currents evoked by ultrafast perfusion of brief pulses of GABA to acutely isolated neurons. Half-maximal effects on currents elicited by 1 mM GABA were elicited by submicromolar concentrations of AAS for neurons from both brain regions. In addition, the efficacy of 10−5to 10−2M GABA was significantly increased by 1 μM 17α-meT. Previous studies have demonstrated a striking dichotomy in receptor composition between the VMN and the mPOA with regard to γ subunit expression. To determine if the preferential expression of γ2subunit-containing receptors in the VMN and of γ1subunit-containing receptors in the mPOA could account for the region-specific effects of AAS in the two regions, responses elicited by ultrafast perfusion of GABA to human embryonic kidney 293 cells transfected with α2, β3, and γ2or α2, β3, and γ1subunit cDNAs were analyzed. As with native VMN neurons, positive modulation of GABA responses was elicited for α2β3γ2recombinant receptors, while negative modulation was induced at α2β3γ1receptors as in the mPOA. Our data demonstrate that AAS in doses believed to occur in steroid abusers can induce significant modulation of GABAergic transmission in brain regions essential for neuroendocrine function. In addition, the effects of these steroids can vary significantly between brain regions in a manner that appears to depend on the subunit composition of GABAAreceptors expressed.
Multi-Joint Coordination During Walking and Foothold Searching in theBlaberusCockroach. II. Extensor Motor Neuron Pattern
Authors: Tryba Andrew K. , Ritzmann Roy E.
Published: December 2017

In a previous study, we combined joint kinematics and electromyograms (EMGs) to examine the change in the phase relationship of two principal leg joints during walking and searching. In this study, we recorded intracellularly from motor neurons in semi-intact behaving animals to examine mechanisms coordinating extension at these leg joints. In particular, we examined the change in the phase of the coxa-trochanter (CTr) and femur-tibia (FT) joint extension during walking and searching. In doing so, we discovered marked similarities in the activity of CTr and FT joint extensor motor neurons at the onset of extension during searching and at the end of stance during walking. The data suggest that the same interneurons may be involved in coordinating the CTr and FT extensor motor neurons during walking and searching. Previous studies in stick insects have suggested that extensor motor neuron activity during the stance phase of walking results from an increase in tonic excitation of the neuron leading to spiking that is periodically interrupted by centrally generated inhibition. However, the CTr and FT extensor motor neuron activity during walking consists of characteristic phasic modulations in motor neuron frequency within each step cycle. The phasic increases and decreases in extensor EMG frequency during stance are associated with kinematic events (i.e., foot set-down and joint cycle transitions) during walking. Sensory feedback associated with these events might be responsible for phasic modulation of the extensor motor neuron frequency. However, our data rule out the possibility that sensory cues resulting from foot set-down are responsible for a decline in CTr extensor activity that is characteristic of the Blaberusstep cycle. Our data also suggest that both phasic excitation and inhibition contribute to extensor motor neuron activity during the stance phase of walking.