bluuebunny/crossref_metadata_2025 huggingface dataset:
Influence of VPM afferents on putative inhibitory interneurons in S1 of the awake rabbit: evidence from cross-correlation, microstimulation, and latencies to peripheral sensory stimulation
Authors: Swadlow H. A.
Published: December 2017

1. Responses of thalamocortical projection neurons and suspected cortical interneurons (SINs) to very brief peripheral stimuli were examined within the vibrissae, the sinus hair, the lip, and the chin representations of ventroposterior medial thalamus (VPM) and primary somatosensory cortex (S1). VPM thalamocortical neurons (N = 40) were identified by their antidromic activation after electrical stimulation of S1. SINs were identified by a high-frequency (> 600 Hz) burst of three or more spikes elicited by suprathreshold stimulation of one or more afferent pathways. SINs also had spikes of very short duration. 2. Previous work has shown that electrical stimulation of VPM elicits a very early and powerful synaptic response in many S1 SINs. Three experimental strategies were employed to test the hypothesis that such responses reflect a monosynaptic VPM input onto SINs and to examine the effects of such input. 1) After a brief peripheral stimulus, the arrival times of VPM thalamocortical impulses in S1 were determined and compared with the initial response times of S1 SINs. 2) Shift-corrected cross-correlograms (CCGs) were constructed from the spike trains of pairs of VPM neurons and SINs that were in precise topographic alignment. 3) Inferences of connectivity based on such CCGs were supported by applying very low-intensity (1-10 microA) microstimulation pulses to the recording microelectrode in VPM and observing evoked responses in the cortical SIN. 3. VPM thalamocortical neurons responded to a brief air puff stimulus at a median latency of 5.05 ms, and the estimated arrival time of the VPM impulses at S1 had a median value of 5.97 ms. This estimate was obtained by adding the antidromic latency of each VPM neuron to the latency of the peripheral stimulus and was supported by similar values obtained from three VPM thalamocortical axons recorded near their termination site within S1. SINs of S1 were among the first cortical neurons to respond to the peripheral stimulus, responding to the air puff at a median latency of 6.6 ms (range 5.7-13.0 ms). The latency of SINs to the peripheral stimulus was strongly related to the latency to gross electrical stimulation of VPM (median value 1.52 ms, r2 = +0.44, P < 0.0001). Many SINs (23 of 34) showed significant shift-corrected CCGs with VPM neurons that were in precise topographic alignment. Most significant CCGs revealed a very brief increase in SIN spike probability (half-amplitude response of approximately 1 ms) that reached a peak value at intervals of 1.4-2.0 ms after the VPM spike.(ABSTRACT TRUNCATED AT 400 WORDS)
Interaction of opioids and membrane potential to modulate Ca2+ channels in rat dorsal root ganglion neurons
Authors: Womack M. D. , McCleskey E. W.
Published: December 2017

1. Using patch-clamp methods, we show that brief prepulses to very positive voltages increase (facilitate) the amplitude of current through Ca2+ channels during a subsequent test pulse in some, but not all, dorsal root ganglion (DRG) sensory neurons. The amplitude of this facilitated current generally increases when the Ca2+ channels are inhibited by activation of the mu-opioid receptor. 2. The facilitated current is blocked by omega-conotoxin GVIA, activates in the range of high-threshold Ca2+ channels, and inactivates at relatively negative holding voltages. Thus facilitated current passes through N-type Ca2+ channels, the same channels that are inhibited by opioids and control neurotransmitter release in sensory neurons. 3. Although maximal facilitation occurs only at unphysiologically high membrane potentials (above +100 mV), some facilitation is seen after prepulses to voltages reached during action potentials. After return to the holding potential, facilitation persists for hundreds of milliseconds, considerably longer than in other neurons. Brief trains of pulses designed to mimic action potentials caused small facilitation (19% of maximal) in a fraction (8 of 24) of opioid-inhibited neurons. 4. We conclude that 1) prepulses to extremely positive voltages can cause partial recovery of Ca2+ channels inhibited by opioids; and 2) small, but detectable, facilitation is also seen after physiological stimulation in some DRG neurons. Facilitation, largely considered a biophysical epiphenomenon because of the extreme voltages used to induce it, appears to be physiologically relevant during opioid inhibition of Ca2+ channels in DRG neurons.
Mechanosensitive currents in putative aortic baroreceptor neurons in vitro
Authors: Cunningham J. T. , Wachtel R. E. , Abboud F. M.
Published: December 2017

1. Whole cell patch-clamp experiments were conducted to determine whether rat aortic baroreceptor neurons contain mechano-sensitive conductances. 2. Putative aortic baroreceptor neurons in the nodose ganglia were identified by injecting DiI onto the adventitia of the aortic arch. Nodose ganglia neurons were dissociated after > or = 1 wk. A fluorescein-conjugated tetanus toxin fragment was used to confirm that the cells labeled with DiI in culture were neurons. 3. Hypoosmotic stretch significantly increased the conductance of DiI-labeled neurons (n = 19). The reversal potential of the response was -11 +/- 1 (SE) mV. 4. In experiments on unlabeled neurons, only 7 of 13 cells showed increases in conductance. BC3H1 cells, a mouse tumor cell line, showed no changes in conductance. 5. Gadolinium (20 microM), a putative blocker of mechanosensitive channels, prevented the increase in conductance produced by hypoosmolality in seven of seven labeled cells. Equimolar concentrations of lanthanum (n = 6) and omega-conotoxin GVIA (1 microM, n = 4), which block voltage-gated calcium channels, failed to significantly affect the inward current.
Alpha-subunit of calcium/calmodulin-dependent protein kinase II enhances gamma-aminobutyric acid and inhibitory synaptic responses of rat neurons in vitro
Authors: Wang R. A. , Cheng G. , Kolaj M. , Randic M.
Published: December 2017

1. Here we report that in acutely isolated rat spinal dorsal horn neurons, the gamma-aminobutyric acid-A (GABAA) receptor can be regulated by calcium/calmodulin-dependent protein kinase II (CaM-KII). Intracellularly applied, the alpha-subunit of CaM-KII enhanced GABAA-receptor-activated current recorded with the use of the whole cell patch-clamp technique. This effect was associated with reduced desensitization of GABA responses. 2. GABA-induced currents are also potentiated by calyculin A, an inhibitor of protein phosphatases 1 and 2A. 3. Conventional intracellular recordings were made from hippocampal CA1 neurons in slices to determine the effect of intracellular application of CaM-KII on inhibitory synaptic potentials evoked by electrical stimulation of the stratum oriens/alveus. The inhibitory synaptic potential was enhanced by CaM-KII; this mechanism may contribute to long-term enhancement of inhibitory synaptic transmission and may also play a role in other forms of plasticity in the mammalian brain.
Properties of superior vestibular nucleus flocculus target neurons in the squirrel monkey. I. General properties in comparison with flocculus projecting neurons
Authors: Zhang Y. , Partsalis A. M. , Highstein S. M.
Published: December 2017

1. Using single-unit recording and microstimulation methods, a group of flocculus target neurons (FTNs) were identified in the superior vestibular nucleus (SVN) and were studied using visual-vestibular interaction paradigms in alert squirrel monkeys. The response properties of these FTNs were characterized and compared with those of flocculus projecting neurons (FPNs). 2. FTNs were monosynaptically inhibited by single-pulse flocculus stimulation. The mean inhibition latency was 1.0 +/- 0.57 (SD) ms (n = 40) and the mean inhibition period was 6.7 +/- 2.69 ms. FTNs were also monosynaptically activated by VIIIth nerve stimulation. The mean response latency was 1.10 +/- 0.25 ms (n = 12). This is about the same as that of the FPNs (1.14 +/- 0.16 ms, n = 17). 3. The most characteristic response property of the FTNs is their firing rate modulation during visual following eye movements induced by sinusoidal rotation of an optokinetic drum at 0.5 Hz. This modulation was mainly related to eye velocity and was therefore termed a visual following eye velocity signal. The average eye velocity gain for all FTNs is 0.79 spikes.s-1.deg-1.s-1. In contrast, the responses of FPNs were not modulated under the same conditions. 4. Even though FTNs are inhibited by the flocculus, they have a relatively higher mean firing rate (124 +/- 23 spikes/s, n = 45) than FPNs (66 +/- 28 spikes/s, n = 42). The underlying mechanism may be related to commissural facilitation of FTNs and commissural inhibition of FPNs. 5. Thirty FTNs were identified as upward eye velocity FTNs because their firing rate increased for upward eye velocity during a visual following eye movement. The mean eye velocity sensitivity was 1.09 spikes.s-1.deg-1.s-1. Most of these cells also modulated during vestibuloocular reflex (VOR) in the dark, with firing rate increasing for downward head velocity. During VOR suppression the firing rate either did not modulate or modulated in phase with head or drum velocity with a smaller amplitude in comparison with the response during visual following. For all cells (with 1 exception) the response during a visual following eye movement can be approximately predicted by a linear vectorial subtraction of the response during VOR suppression and the response during VOR in the dark [modulation response vector of FTNs during visual following of the optokinetic stimulus (OKR) approximately modulation response vector of FTNs during VOR suppression-modulation response vector of FTNs during VOR in the dark].(ABSTRACT TRUNCATED AT 400 WORDS)
Mechanisms controlling human head stabilization. II. Head-neck characteristics during random rotations in the vertical plane
Authors: Keshner E. A. , Cromwell R. L. , Peterson B. W.
Published: December 2017

1. In this study we have tested the hypothesis that the mechanisms controlling stabilization of the head-neck motor system can vary with both the frequency and spatial orientation of an externally applied perturbation. Angular velocity of the head with respect to the trunk (neck) and myoelectric activity of two neck muscles (semispinalis capitis and sternocleidomastoid) were recorded in eight seated subjects during pseudorandom rotations of the trunk in the vertical (pitch) plane. Subjects were externally perturbed with a random sum-of-sines stimulus at frequencies ranging from 0.35 to 3.05 Hz. Four instructional sets were presented. Voluntary mechanisms were examined by having the subjects actively stabilize the head in the presence of visual feedback as the body was rotated (VS). Visual feedback was then removed, and the subjects attempted to stabilize the head in the dark as the body was rotated (NV). Reflex mechanisms were examined when subjects performed a mental arithmetic task during body rotations in the dark (MA). Finally, subjects performed a voluntary head tracking task while the body was kept stationary (VT). 2. In VS and NV, gains and phases of head velocity indicated good compensation for the perturbation at frequencies up to 2 Hz. Between 2 and 3 Hz, gains dropped slowly and then steeply descended above 3 Hz as phases became scattered. 3. In MA, gains were lower and exhibited more scatter than in VS and NV at frequencies < 1 Hz. Phases around -180 degrees indicated that compensatory activity was occurring even with these low gains. Between 1 and 2 Hz, response gains steeply ascended, implying that reflex mechanisms were becoming the predominant mechanism for compensation in this frequency range. Above 2 Hz, gains dropped off to 0.5 and lower, but phases remained close to -180 degrees, suggesting that the reflex mechanisms were not dominant in this frequency range, but that they were still contributing toward compensation for the trunk perturbation. 4. Neck muscle electromyographic (EMG) responses were similar in VS, NV, and MA, demonstrating decreasing gains between 0.35 and 1.5 Hz, and then increasing beyond the previous high level of activation. This U-shaped response pattern implies an enhanced participation of neural mechanisms, probably of reflex origin, in the higher frequency range. 5. Patterns observed during external perturbations of the trunk were not apparent in the response dynamics of voluntary head tracking. In VT, subjects successfully tracked the stimulus only at the lowest frequencies of head movement.(ABSTRACT TRUNCATED AT 400 WORDS)
Activity of rostral trigeminal sensory neurons in the cat during wakefulness and sleep
Authors: Cairns B. E. , Fragoso M. C. , Soja P. J.
Published: December 2017

1. Relatively little is known about the activity of trigeminal sensory neurons during naturally occurring behavioral states of sleep and wakefulness. Accordingly, experiments were performed in chronic unanesthetized behaving cats in which neuronal activity in the rostral trigeminal sensory nuclear complex (TSNC) was recorded extracellularly in response to low-intensity stimulation of mandibular and maxillary divisions of cranial V nerve. The peripheral responses of TSNC neurons were evaluated during naturally occurring episodes of wakefulness, quiet sleep, and active sleep. 2. The location of the rostral TSNC was confirmed by recording characteristic orthodromic field potentials generated in response to afferent volleys from tooth pulp and inferior alveolar (IAN) nerve stimuli. Antidromic fields from the trigeminal (MotV) and facial (MotVII) motor pools were used to demarcate the anterior and posterior limits of the rostral TSNC (i.e., main sensory nucleus and nucleus oralis pars gamma). 3. In the absence of peripherally applied stimuli, individual rostral TSNC neurons recorded in the chronic, unanesthetized cat during the behavioral state of wakefulness did not display ongoing spike activity. 4. The response characteristics of individual TSNC neurons to low-intensity stimuli delivered to V afferents emanating from the canine tooth pulps during the behavioral state of drowsy wakefulness consisted of a short train of action potentials characterized by a short latency-to-onset (7.2 +/- 0.4 ms, mean +/- SE, n = 51). TSNC neurons fell into two categories on the basis of their response to graded intensities of tooth pulp stimuli. "Stimulus intensity-dependent" neurons demonstrated evoked responses that had a response profile that increased with stimulus intensity. In contrast, the response profile of "stimulus intensity-independent" neurons remained stable irrespective of the stimulus intensity used. 5. During episodes of wakefulness and quiet sleep, IAN-evoked orthodromic fields did not differ in their amplitude or other waveform parameters. However, during active sleep, the IAN-evoked orthodromic field potential was suppressed by an average of 28% as compared with wakefulness. 6. The number of action potentials evoked by consecutive presentation of low-intensity tooth pulp stimuli were compared during sleep and wakefulness. The evoked responses were suppressed during active sleep (29%, n = 42). Suppression observed during active sleep occurred in both ("stimulus-dependent" and "stimulus-independent") groups of TSNC neurons. During the phasic rapid-eye-movement (REM) episodes of active sleep, both the orthodromic field potentials and unitary action potentials were further suppressed or abolished. 7. The conclusion is reached that synaptic transmission through the rostral trigeminal sensory nucleus is dependent on the behavioral state of the animal.(ABSTRACT TRUNCATED AT 400 WORDS)
Inhibition of canine H reflexes during locomotor-like rotation about the knee arises from muscle mechanoreceptors in quadriceps
Authors: Misiaszek J. E. , Barclay J. K. , Brooke J. D.
Published: December 2017

1. H reflexes were elicited in the small muscles of the foot in the canine and human during passive locomotor-like rotation of the shank about the ipsilateral knee. The movement-induced effect was similar in the two species. In the anesthetized dog, the reflex gain was reduced by 36 +/- 8.4% (mean +/- SE) on average, compared with appropriate stationary controls. Reflexes in the human were reduced during movement to 45 +/- 3.5% of their stationary control values. 2. H reflexes were elicited in the anesthetized dog during passive locomotor-like rotation about the knee and were compared with reflexes obtained with the limb stationary. Populations of mechanoreceptors were then systematically removed to ascertain which group or groups provided the sensory input that leads to the decrease in reflex gain during movement. We hypothesized that the majority of the reflex attenuation could be attributed to muscle mechanoreceptors. 3. Reflexes continued to be significantly reduced (P < 0.05) during passive movement about the knee until the muscle mechanoreceptors of the quadriceps muscle group were deactivated. The removal of input from joint receptors or cutaneous receptors did not eliminate the gain reduction induced by the passive movement. 4. It is concluded that muscle mechanoreceptors of the quadriceps muscle group provide an inhibitory input to the H reflex pathway of the dog plantar muscle when the knee is passively moved in a locomotor-like fashion. This source of inhibition likely also contributes to the soleus H reflex gain reduction in humans.
Learning a visuomotor transformation in a local area of work space produces directional biases in other areas
Authors: Ghilardi M. F. , Gordon J. , Ghez C.
Published: December 2017

1. The dependence of directional biases in reaching movements on the initial position of the hand was studied in normal human subjects moving their unseen hand on a horizontal digitizing tablet to visual targets displayed on a vertical computer screen. 2. When initial hand positions were to the right of midline, movements were systematically biased clockwise. Biases were counterclockwise for starting points to the left. Biases were unaffected by the screen location of the starting and target positions. 3. Vision of the hand in relation to the target before movement, as well as practice with vision of the cursor during the movement, temporarily eliminated these biases. The spatial organization of the biases suggests that, without vision of the limb, the nervous system underestimates the distance of the hand from an axis or plane that includes its most common operating location. 4. To test the hypothesis that such an underestimate might represent an adaptation to a local area of work space or range effect, subjects were trained to reach accurately from right or left positions. After training, movements initiated from other locations, including ones that were previously error free, showed new biases that again represented underestimates of the distance of the initial hand position from the new trained location. 5. We conclude that hand path planning is dependent on learned representations of the location of the hand in the work space.
Input-output properties of hand-related cells in the ventral cingulate cortex in the monkey
Authors: Cadoret G. , Smith A. M.
Published: December 2017

1. Neurons with proprioceptive or cutaneous receptive fields associated with the hand were identified in the ventral bank of the cingulate sulcus in the monkey. Cells with proprioceptive fields outnumbered cells receiving cutaneous afferents by more than three to one. No cells were encountered that received convergent proprioceptive and cutaneous input. The high concentration of these neurons in the lateral depth of the cingulate sulcus establishes that a distinct hand representation exists within the rostral part of area 23c. 2. Hand-related neurons in area 23c exhibited strong activity modulations during grasping, lifting, and holding an object with the contralateral thumb and index finger. Force pulse perturbations applied to the object elicited excitatory responses at latencies of approximately 45 ms. The modulation of the cellular activity and the input-output properties of these cingulate neurons suggest that, like neurons of primary motor and sensory cortex, these cingulate neurons are also involved in the sensorimotor control of finger movements.
Kinematics of spontaneous, reflex, and conditioned eyelid movements in the alert cat
Authors: Gruart A. , Blazquez P. , Delgado-Garcia J. M.
Published: December 2017

1. Upper eyelid position and velocity, and the electromyographic (EMG) activity of the orbicularis oculi muscle, were recorded bilaterally in alert cats during spontaneous, reflexively evoked, and conditioned eyelid movements. 2. Spontaneous blinks appeared randomly (0.2-0.5 per min) and consisted of a fast, large downward lid movement followed by a slower up phase. Blinks of smaller amplitude and slower velocity were also observed mainly accompanying behavioral movements, such as during peering and grimacing. 3. Eyelid response to air puffs applied to the cornea and tarsal lid skin consisted of a short-latency (9-16 ms), fast (up to 2,000 degrees/s) downward movement that lasted for 25-30 ms, followed by late, small downward sags that were sometimes still evident after stimulus offset. Blinks outlasted the duration of the stimulus by approximately 150 ms. Blinks elicited by flashes of light or tones showed longer latency (47.3 +/- 6.3 and 53.7 +/- 8.0 ms, mean +/- SD; respectively), smaller amplitude, and a quicker habituation than air-puff-evoked lid responses. 4. For the down phase of the blink, the peak velocity, but not its duration, increased linearly with blink amplitude. Because the rise time of the down phase remained constant, changes in blink amplitude seemed to be the result of increased blink velocity. The down phase of a typical 10 degrees blink was 10 times faster than the up phase of the same blink or than upward and downward lid saccades of the same amplitude. The peak velocity and duration of the up phases of reflex blinks and upward and downward lid saccades increased linearly with lid movement amplitude. 5. The initial down phase of air-puff-evoked blinks decreased in latency, increased in amplitude and peak velocity, and maintained the same rise time for increasing puff pressure. None of these parameters was dependent on puff duration. The duration of the blink also increased linearly with air puff duration. 6. The amplitude of air-puff-evoked blinks was inversely related to lid position, decreasing with further lid positions in the closing direction. In contrast, neither peak nor integrated EMG activity of the orbicularis oculi muscle was affected by lid position, being only a function of stimulus parameters and of the animal's level of alertness. 7. Air puffs > 20 ms and > 1 kg/cm2 evoked two successive bursts (R(ap) 1 and R(ap) 2) in the EMG activity of the orbicularis oculi muscle. Shorter and/or weaker stimuli evoked only the R(ap) 1 response.(ABSTRACT TRUNCATED AT 400 WORDS)
Human cortical regions activated by wide-field visual motion: an H2(15)O PET study
Authors: Cheng K. , Fujita H. , Kanno I. , Miura S. , Tanaka K.
Published: December 2017

1. Several areas in the monkey dorsal visual pathway, including the dorsal part of the medial superior temporal area, have been found to contain cells responding to movements of a wide visual field and are suggested to be involved in analyzing self-induced motion information. In the present study, positron emission tomography was used to localize human cortical regions responding to wide-field visual motion. Changes in regional cerebral blood flow (rCBF) were measured when subjects maintained fixation and viewed low-contrast (0.15 log units brighter than the background) dots subtending 80 x 80 degrees and moving either coherently or incoherently. Brain foci were localized after activity in a fixation-only paradigm was subtracted from that in the two moving dot paradigms. 2. Both the coherent and incoherent movements significantly activated the primary/secondary visual cortex and surrounding visual areas in the cuneus and superior occipital gyrus. Subtraction of images between the coherent and incoherent movements showed that the activity caused by the two types of movement was comparable in these early visual cortical regions. 3. In the lateral occipitotemporoparietal cortex, the coherent movement specifically activated two separate areas; a posterior focus was located at the border of the right occipitotemporal gyri, and a dorsoanterior focus was located bilaterally in the temporoparietal cortex. The incoherent movement did not activate these regions. 4. A fine anatomic localization using individual magnetic resonance images was performed for the bilateral activation in the temporoparietal cortex, which was found to be located mainly in the depth of the inferior parietal lobule and a small portion of the superior and middle temporal gyri. 5. Both the coherent and incoherent movements activated a part of the superior parietal lobule located within the intraparietal sulcus (Brodmann area 7). The bilateral foci activated by the coherent movement were located more anteriorly than the focus activated by the incoherent movement. Subtraction images between the coherent and incoherent movements, however, did not reveal any significant rCBF increases in the superior parietal lobule. 6. Several other cortical regions known to be involved in visuospatial and visuomotor functions were also activated by the coherent movement, including the frontal eye field (Brodmann area 8) and premotor cortex (Brodmann area 6) in the frontal lobe. 7. The posteriorly located activation at the border of occipito-temporal gyri corresponds to the homologue of the middle temporal area reported in previous activation studies using small to medium-sized motion stimuli. The bilateral activation in the inferior parietal lobule appeared to rely on wide-field motion stimulation.
Calcium channel involvement in GABAB receptor-mediated inhibition of GABA release in area CA1 of the rat hippocampus
Authors: Doze V. A. , Cohen G. A. , Madison D. V.
Published: December 2017

1. Experiments were performed in rat hippocampal slices to examine the nature of GABAergic inhibition of inhibitory synaptic transmission. In these experiments the effects of the gamma-aminobutyric acid-B (GABAB) receptor agonist, baclofen, and of subtype-selective calcium channel blockers were tested with the use of intracellular recordings of evoked inhibitory postsynaptic potentials (IPSPs) and whole cell recordings of spontaneous GABAergic inhibitory postsynaptic currents (IPSCs). 2. Baclofen inhibited evoked and spontaneous (action-potential-dependent) monosynaptic GABAA-mediated IPSPs and IPSCs but had no effect on the frequency of tetrodotoxin-resistant (action-potential-independent) miniature IPSCs recorded in CA1 pyramidal neurons. 3. Depolarizing GABAergic synaptic terminals by raising the extracellular potassium concentration caused an increase in action-potential-independent miniature IPSC frequency that could be inhibited by either baclofen or cadmium, a blocker of voltage-dependent calcium channels. In addition, under these depolarizing conditions, cadmium occluded the baclofen inhibition of miniature IPSCs. These data suggest that baclofen reduces only depolarization-induced, not quantal, GABA release and that it does so by decreasing presynaptic voltage-dependent calcium influx. 4. Experiments with subtype-selective calcium channel blockers demonstrate that the presynaptic action of baclofen was mediated through both omega-conotoxin-GVIA-sensitive and omega-agatoxin-IVA-sensitive, but not dihydropyridine-sensitive calcium channels.
Nine members of the myomodulin family of peptide cotransmitters at the B16-ARC neuromuscular junction of Aplysia
Authors: Brezina V. , Bank B. , Cropper E. C. , Rosen S. , Vilim F. S. , Kupfermann I. , Weiss K. R.
Published: December 2017

1. Neuromodulation by multiple related peptides with different spectra of physiological effects appears an effective way to integrate complex physiological functions. A good opportunity to examine this issue occurs in the accessory radula closer (ARC) neuromuscular circuit of Aplysia, where, extensive previous work has shown, acetylcholine-induced contractions of the muscle are variously modulated by several families of peptide cotransmitters released under appropriate behavioral circumstances from the muscle's own two motor neurons. 2. In this work we focused on the myomodulins (MMs) released from motor neuron B16. Previous work has characterized MMA (PMSMLRLamide) and MMB (GSYRMMRLamide). We now similarly purified from ARC neuromuscular material and sequenced MMC (GWSMLRLamide), MMD (GLSMLRLamide), MME (GLQMLRLamide), and MMF (SLNMLRLamide). Three additional MMs, MMG (TLSMLRLamide), MMH (GLHMLRLamide), and MMI (SLSMLRLamide), are encoded by a known MM gene. B16 probably synthesizes, and coreleases, all nine MMs. Further MMs have been found in other mollusks. All evidence indicates that the MMs are a major, widely distributed family of molluscan neuropeptides important as neuromuscular modulators and probably also central transmitters or modulators. 3. MM effects on motor neuron B16-elicited ARC muscle contractions were best analyzed as the sum of three distinct actions: potentiation, depression of the amplitude of the contractions, and acceleration of their relaxation rate. We compared the effectiveness of all nine MMs in these respects. We correlated this with their effectiveness in enhancing the L-type Ca current and activating a specific K current in voltage-clamped dissociated ARC muscle fibers, effects we previously proposed to underlie, respectively, the potentiation and the depression of contractions. 4. All nine MMs were similarly effective in enhancing the Ca current and, as far as it was possible to determine, potentiating the amplitude as well as accelerating the relaxation rate of the contractions. 5. In contrast, the MMs' ability to activate the K current and depress the contractions varied greatly. MMB and MMC, in particular, were weak, whereas the other seven MMs were considerably more effective in both respects. 6. Altogether, we were able to explain the potentiating and depressing strengths of the MMs by the magnitude of their modulation of the Ca and K currents, providing further support for our hypothesis that the effects on contraction amplitude are mediated by the effects on the two currents. 7. The net effect on contraction amplitude was determined by the balance between the potentiation and depression. Although most MM concentrations had both potentiating and depressing actions, potentiated contractions predominated at low and depressed contractions (but with accelerated relaxation rate) at high concentrations.(ABSTRACT TRUNCATED AT 400 WORDS)
Serial E-M and simulation study of presynaptic inhibition along a group Ia collateral in the spinal cord
Authors: Walmsley B. , Graham B. , Nicol M. J.
Published: December 2017

1. A muscle spindle primary afferent (group Ia) was physiologically identified and labeled intracellularly with the use of horseradish peroxidase (HRP) in the cat lumbar spinal cord. Serial-section electron microscopy (EM) was used to examine and reconstruct an entire axon collateral and its branches within Clarke's column. In the present study the existence and location of presynaptic contacts on Ia afferent boutons along these collateral branches were determined from examination of the serial-section electron-micrographs. 2. Of 36 Ia boutons examined in serial sections along the branches of the same collateral, 3 presynaptic contacts were found. Two of these contacts were made with Ia boutons in a complex nodal region consisting of two unmyelinated side branches exhibiting a total of six Ia boutons. The other presynaptic contact was made with a Ia bouton in a nodal region consisting of two Ia boutons connected by a thin unmyelinated bridge. 3. Computer simulations, based directly on the serial-section-reconstructions, were used to investigate the possible effects of these presynaptic contacts on membrane potential and on a propagating action potential along the Ia collateral. The effect of a presynaptic contact was modeled by a sustained gamma-aminobutyric acid-A (GABAA)-activated chloride conductance. 4. The simulation results indicated that the effect of a presynaptic contact on membrane potential and action-potential amplitude is likely to extend beyond the contacted bouton to other boutons occurring along the short unmyelinated branches arising from the same node.(ABSTRACT TRUNCATED AT 250 WORDS)
Information coding in the rodent prefrontal cortex. II. Ensemble activity in orbitofrontal cortex
Authors: Schoenbaum G. , Eichenbaum H.
Published: December 2017

1. Neural activity was recorded from the orbitofrontal cortex (OF) of rats performing an eight-odor discrimination task that included predictable associations between particular odor pairs. A modified linear discriminant analysis was employed to characterize the population response in each trial of the task as a point in an N-dimensional activity space with the firing rate of each cell in the population represented on one of the N dimensions. The ability of the ensemble to discriminate among conditions of a variable was reflected in the tendency of population responses to cluster together in this activity space for repetitions of a given condition. We assessed coding of several variables describing the period of odor sampling, focusing on aspects of current, past, and future events reflected in single-neuron firing patterns, in ensembles composed of 22-138 cells active during the period when the rats sampled the discriminative stimulus in each trial. 2. OF ensembles performed well at discriminating variables with relevance to task demands represented in single-neuron firing patterns, specifically the physical attributes and assigned reward contingency of the current odor as well as the expectation of reward in the following trial that could be inferred from the predictable associations between particular pairs of odors. OF ensembles were able to correctly identify the identity and assigned reward contingency of the current odor in up to 52% (chance = 12.5%) and 99% (chance = 50%) of all trials, respectively, such that the observed behavioral performance required a population of 5,364 odor-responsive cells in the case of odor identity and only 40 cells in the case of valence. Expectations regarding upcoming rewards based on both assigned response contingency and associations between particular pairs of odors were correctly classified in up to 67% (chance = 20%) of all trials such that the observed level of behavioral performance required a population of 3,169 cells. 3. Other information represented in the single-neuron firing patterns, such as the identity and reward contingency of the preceding odor and specific odor-odor associations, was poorly encoded by OF ensembles. Thus neural ensembles in OF may represent only some of the information reflected in single-neuron activity. Stable coding of only the most useful and relevant information by the ensemble might emerge from the tuning properties of single neurons under the influence of the task at hand, producing in the well-trained animal the observed pattern of broad and diverse coding by single neurons and selective, task-relevant coding by neural ensembles in OF.
Development of spontaneous activity and mechanosensitivity in axotomized afferent nerve fibers during the first hours after nerve transection in rats
Authors: Michaelis M. , Blenk K. H. , Janig W. , Vogel C.
Published: December 2017

1. Spontaneous activity and ectopic mechanical excitability of axotomized unmyelinated and myelinated fibers in the sural nerve were examined in anesthetized rats. The analysis was performed within 30 h after the nerve lesion using single-fiber recordings that were performed proximal to the severed nerve end. 2. Among all unmyelinated fibers tested (n = 865), 4-8% exhibited persistent spontaneous activity of low and irregular frequency. The percentage of spontaneously active C fibers did not change significantly during the first 30 h. Only 6 of 796 A fibers had spontaneous activity. 3. Mechanical stimulation of the cut nerve end excited 5-8% of all C fibers under investigation. No development with time could be detected in the frequency of mechanically excitable C fibers. In contrast, beginning 6 h after nerve transection, the number of mechanically excitable A fibers rose with time, reaching 27% after 22-30 h. 4. Among the A fibers (C fibers) that exhibited mechanical excitability or spontaneous activity, only 4% (25%) had both properties, whereas 96% (75%) were either mechanosensitive or spontaneously active. 5. With time after the nerve lesion, the mean discharge rate of all spontaneously discharging C fibers decreased significantly from 49 imp/min (0.5-9 h after nerve lesion) to 11 imp/min after 22-30 h. The mean discharge rate of C fibers exhibiting solely spontaneous activity and those C fibers that were additionally mechanosensitive did not differ significantly.(ABSTRACT TRUNCATED AT 250 WORDS)
Intracellular Ca2+ stores can account for the time course of LTP induction: a model of Ca2+ dynamics in dendritic spines
Authors: Schiegg A. , Gerstner W. , Ritz R. , van Hemmen J. L.
Published: December 2017

1. A model of Ca2+ dynamics in spines of CA1 hippocampal neurons is presented. In contrast to traditional models, which concentrate on the effects of Ca2+ influx, diffusion, buffering, and extrusion, we also consider the additional effect of intracellular Ca2+ stores. 2. It is shown that traditional models without Ca2+ stores cannot account for the time course of long-term potentiation (LTP) induction as found in recent experiments. Experimental data suggest that the intracellular Ca2+ concentration should be elevated for up to 2 s, whereas the Ca2+ concentration in standard models of Ca2+ dynamics decays much faster. 3. When intracellular Ca2+ stores are taken into account, a much slower decay is found. In particular, a model simulation with a stimulation paradigm consisting of two bursts of four impulses at 100 Hz each and variable interburst intervals can reproduce experimental results found for primed or theta-burst stimulation. 4. In our model, Ca2+ release from the store has a nonlinear, bell-shaped dependence on the intracellular Ca2+ concentration, similar to the one found for inositoltrisphosphate and ryanodine receptors. These receptors are known to control calcium release from intracellular stores. 5. Our model suggests an important role of intracellular calcium stores in the induction of LTP. The stores serve as a long-term calcium source that can sustain an intracellular Ca2+ concentration above the resting level for 1-2 s.
Long-term potentiation of glycinergic inhibitory synaptic transmission
Authors: Oda Y. , Charpier S. , Murayama Y. , Suma C. , Korn H.
Published: December 2017

1. Tetanizing protocols were used to test whether glycinergic inhibition undergoes long-term plasticity in vivo. For this purpose we studied the inhibition evoked disynaptically in the teleost Mauthner (M) cell by stimulation of the posterior branch of the contralateral VIIIth nerve. The advantage of this experimental design is that the inhibition, which is mediated by identified second-order commissural interneurons, is not contaminated by parallel excitation. 2. The VIIIth-nerve-evoked inhibitory postsynaptic potentials (IPSPs), which are generated at the level of the soma, are depolarizing in Cl(-)-loaded M cells. After VIIIth nerve tetanization, these IPSPs exhibited potentiation lasting > 30 min in 23 of 31 cells. The maximum enhancement measured 5-10 min after the onset of the tetanization averaged 100 +/- 19% (mean +/- SE). In contrast, the non-"tetanized" collateral IPSP induced by antidromic stimulation of the M axon did not increase significantly suggesting synaptic specificity of the potentiation. 3. Single-electrode voltage-clamp studies of Cl(-)-loaded M cells indicated that this plasticity is due to an increased synaptic conductance that occurs without obvious modifications of the kinetics or voltage dependence of the inhibitory postsynaptic currents. 4. The synaptic conductance and its changes during potentiation were quantified by measuring the inhibitory shunt of the antidromic spike while recording with potassium-acetate-filled electrodes. For this purpose the ratio, r', of the inhibitory to resting membrane conductances, was calculated using the expression (V/V')--1, where V and V' are the amplitudes of the control and the test antidromic spikes, respectively. This ratio was called fractional conductance. Measured at the peak of the expected VIIIth-nerve-evoked IPSP, r' increased by 114 +/- 18% (n = 46). Again the collateral inhibitory conductance was not modified. 5. Because there are two synapses in the inhibitory pathway, it became important to determine whether modifications of the second-order inhibitory junctions contribute to the overall potentiation. Several experimental procedures were used for this purpose. 6. The input-output relationship at the inhibitory synapses was determined by comparing the size of the presynaptic volley and r'. The former was recorded intra- or extracellularly as a monophasic positive potential, the so-called extrinsic hyperpolarizing potential, which increases in parallel with the strength of VIIIth nerve stimulation. In 12 experiments where the presynaptic volley was unaffected by the tetanization, suggesting lack of involvement of the first relay, r' nevertheless increased in amplitude by 79 +/- 14%.(ABSTRACT TRUNCATED AT 400 WORDS)
Sensorimotor-correlated discharge recorded from ensembles of cerebellar Purkinje cells varies across the estrous cycle of the rat
Authors: Smith S. S.
Published: December 2017

1. In the present study, locomotor-correlated activity of cerebellar Purkinje cells, recorded using arrays of microwires chronically implanted in adult female rats, was examined across estrous-cycle-associated fluctuations in endogenous sex steroids. Ongoing studies from this laboratory have shown that systemic and local administration of the sex steroid 17 beta-estradiol (E2) augments excitatory responses of cerebellar Purkinje cells to iontophoretically applied glutamate, recorded in vivo from anesthetized female rats. In addition, this steroid potentiated discharge correlated with limb movement. For the present study, extracellular single-unit activity was recorded from as many as 5-11 Purkinje cells simultaneously during treadmill locomotion paradigms. Motor modulation of activity was recorded across three to five consecutive estrous cycles from behaviorally identified cohorts of neurons to test the hypothesis that fluctuations in endogenous sex steroids alter motor modulation of Purkinje cell discharge. 2. Locomotor-associated discharge correlated with treadmill locomotion was increased by a mean of 47% on proestrus, when E2 levels are elevated, relative to diestrus 1. These changes in discharge rate during treadmill locomotion were of significantly greater magnitude than corresponding cyclic alterations in discharge during stationary periods. 3. Correlations with the circadian cycle were also significant, because peak levels of locomotor-associated discharge on the night of behavioral estrus, following elevations in circulating E2, were on average 67% greater than corresponding discharge recorded during the light (proestrus). 4. Alterations in the step cycle were also observed across the estrous cycle: significant decreases in the duration of the flexion phase (by 265 ms, P < 0.05) were noted on estrus compared with diestrus. 5. When recorded on estrus, Purkinje cell discharge correlated with the stance or flexion phase of the step cycle was greater in magnitude and preceded the event by an average of 130 ms, compared with values determined on diestrus. 6. On estrus, responses of Purkinje neurons to iontophoretically applied quisqualate were enhanced fourfold after administration of exogenous E2, assessed in urethan-anesthetized female rats. 7. In addition, systemic administration of E2 (30 ng iv) potentiated responses of cerebellar Purkinje cells to electrical stimulation of the forepaw by an average of 150%, recorded in anesthetized female rats. 8. These results are consistent with the hypothesis that elevations in circulating E2 are associated with enhanced discharge of cerebellar Purkinje cells in response to pharmacological or electrical stimuli or associated with locomotor behavior.
Effects of inhibitory amino acid antagonists on reciprocal inhibitory interactions during rhythmic motor activity in the in vitro neonatal rat spinal cord
Authors: Cowley K. C. , Schmidt B. J.
Published: December 2017

1. The role of inhibitory amino acid transmission in the coordination and generation of rhythmic motor activity was examined with the use of an in vitro neonatal rat spinal cord preparation. Before adding gamma-aminobutyric acid (GABA) or glycine receptor agonists and antagonists, rhythmic motor activity was induced by bath application of acetylcholine (ACh), N-methyl-D,L-aspartate (NMA), or serotonin (5-HT) while monitoring bilateral ankle flexor and extensor electroneurograms (ENGs). The timing of rhythmic flexor and extensor discharge was consistent with that seen during overground locomotion in 27% of 84 bath applications of these substances (n = 65 preparations). 2. Subsequent addition of the GABAA receptor agonist muscimol, the GABAB receptor agonist baclofen, or glycine, abolished rhythmic activity in 95% of the tested applications. 3. GABAB receptor blockade did not disrupt alternating patterns of ENG discharge. However, addition of the GABAA receptor antagonist bicuculline, or the glycine receptor antagonist strychnine, transformed alternating flexor-extensor and left-right activity into patterns characterized by bilaterally synchronous rhythmic activation of all hindlimb ENGs. The onset of individual ENG bursts was more abrupt following bicuculline or strychnine. Strychnine also synchronized high-frequency (4-8 Hz) packets of rhythmic discharge within ENG bursts. 4. Some preparations developed synchronous, but unstable, rhythmic activity in the presence of bicuculline or strychnine alone. However, NMA, 5-HT, or ACh was usually required in addition to these antagonists to promote sustained rhythmic activity.(ABSTRACT TRUNCATED AT 250 WORDS)