bluuebunny/crossref_metadata_2025 huggingface dataset:
Similarity of granular-induced inhibitory periods in pairs of neighboring mitral/tufted cells
Authors: Buonviso N. , Chaput M. A. , Berthommier F.
Published: December 2017

1. Neighboring mitral/tufted cells have been previously shown to present temporal correlations of their firings related to the respiratory rhythm, particularly under odor stimulation. This occurs despite the existence of a powerful inhibitory control exerted by granule cells onto mitral/tufted cells. In the present study, we hypothesized that neighboring mitral cells can present granular induced inhibitory periods with similar latencies and durations and that such a similarity would preserve them from a possible suppression of their temporal correlations. 2. To test this hypothesis, we analyzed the latencies and durations of the inhibitory periods induced by granular activation in pairs of simultaneously recorded neighboring mitral cells. The activation of granule cells was achieved by electrical stimulation of the different pathways known to directly activate granule cells [lateral olfactory tract (LOT), anterior limb of the anterior commissure (AC), and piriform cortex (PC)]. Data from this group were compared with those of a control group composed of distant cells also recorded simultaneously. 3. Results first show that the latencies to onset of inhibition or to recovery were more frequently similar in neighboring cells than in control cells and that this similarity was enhanced by odor stimulation. Second, the probability that two cells exhibit similar inhibitory periods (i.e., similar latencies to both onset and to recovery) in response to electrical stimulation of LOT, AC, or PC was significantly higher in neighboring than in control cells. Third, only neighboring cells were found to present similar inhibitory periods in response to the stimulation of all of the three structures. 4. Granular activation was also found to modify the temporal patterns of individual mitral cells. However, although these patterns were not systematically modified similarly in neighboring mitral cells, they remained perfectly synchronized with zero delay if they were already synchronous without electrical stimulation. On the contrary, if patterns were spontaneously uncorrelated, electrical stimulation never produced a synchronization of their firings, even if their temporal relationships could be profoundly modified. 5. These results show that neighboring mitral cells can receive granular-induced inhibition with similar latencies and durations with a probability much higher than control cells. Such similarities allow neighboring mitral cells to preserve their temporal correlation despite the powerful inhibitory input from granule cells. Functional hypotheses about the role of the cortical feedback projections onto the bulb are discussed.
Alpha 1 adrenoceptor activation potentiates taurine response mediated by protein kinase C in substantia nigra neurons
Authors: Nabekura J. , Omura T. , Horimoto N. , Ogawa T. , Akaike N.
Published: December 2017

1. The potentiation of glycine receptor-mediated taurine response (Itau) by alpha 1 adrenoceptor activation was investigated in neurons freshly dissociated from the rat substantia nigra (SN) using a nystatin perforated-patch recording. 2. Norepinephrine (NE) at a concentration of 10(-4) M in the presence of 10(-5) M yohimbine and 10(-5) M propranolol potentiated the peak amplitude of Itau (10(-3) M) at a holding potential of -40 mV under voltage clamp conditions. NE could be substituted by phenylephrine at this potentiation. 3. This potentiation of the taurine response persisted in the treatment with pertussis toxin (500 ng/ml) for 18 h. The intracellular application of GDP-beta S (100 microM) with a conventional whole cell patch recording mode abolished the effect of alpha 1 adrenoceptor activation on the Itau. 4. Staurosporine (10(-7) M) blocked the enhancement of Itau by 10(-4) M NE with 10(-5) M yohimbine and 10(-5) M propranolol. In additional phorbol-12-myristate 13-acetate (10(-5) M) potentiated Itau. 5. The intracellular application of 0.275 U/ml protein kinase C (PKC) with a conventional whole cell configuration gradually increased the peak amplitude of Itau. On the other hand, intracellular perfusion either without PKC or with PKC plus 4 microM PKC (19-36), a PKC inhibitor, did not potentiate Itau. 6. A single channel recording in a cell attached configuration revealed that NE (10(-4) M) with 10(-5) M yohimbine and 10(-5) M propranolol increased the total open time of the taurine-activated channel. This increase of the channel opening was antagonized by staurosporine (10(-7) M). 7. Neither tapsigargin (10(-6) M), LiCl (10(-4) M), trifluoperazine (10(-5) M) nor (S)-5-isoquinolinesulfonic acid, 4-[2-[(5-isoquinolinylsulfonyl) methylamino]-3-oxo-(4-phenyl-1-piperazinyl)-propyl]phenyl ester (10(-4) M) applied in the perfusate were found to affect the potentiation of Itau by alpha 1 adrenoceptor. The intracellular application of inositol triphosphates (10(-4) M) in a conventional whole cell recording also had no effect on Itau. 8. These findings thus indicate that alpha 1 adrenoceptor coupled with pertussis-insensitive G protein increases the intracellular PKC activity, thus leading to an increase in the channel opening activated by taurine and an enhancement of the peak amplitude of Itau in the SN neurons.
Age-related loss of activity of auditory-nerve fibers
Authors: Schmiedt R. A. , Mills J. H. , Boettcher F. A.
Published: December 2017

1. Characteristic frequencies (CF), spontaneous rates (SR), and thresholds were recorded from single fibers in the auditory nerves of gerbils aged for 36 mo in a quiet vivarium. The data from the quiet-aged animals were compared with similar data obtained previously from young controls. Fibers were classified as "low-SR" if their spontaneous rates were < or = 18 spikes/s and "high SR" for higher rates. 2. For CFs > 6 kHz, the percentage of low-SR fibers contacted declined from 57% of the population in young gerbils to 29% in the aged gerbils. This population change is statistically significant (P < 0.01). At CFs < 6 kHz, the population demographics did not change significantly with age, with the low-SR fibers comprising 30 and 39% of the population, respectively, for the young and aged animals. 3. To further test the hypothesis that low-SR fibers with CFs > 6 kHz become less active with age, additional experiments were conducted to examine the recovery of the compound action potential (CAP) response from prior high-level stimuli. Previous work has shown that the CAP recovery curve has two segments: a fast segment associated with the high-SR fibers and a slow segment associated with the low-SR fibers. The curves obtained from quiet aged gerbils show a faster recovery than young controls for probe tones at 8 and 16 kHz, but not at 2 and 4 kHz. Thus these results agree with our single-fiber data indicating that there is a loss of low-SR activity for CFs > 6 kHz in the aged animals. 4. Low-SR fibers typically have larger dynamic ranges than those of high-SR fibers, are better able to preserve information concerning stimulus timing and amplitude modulation, and their responses are more robust in the presence of masking noise. Moreover, low-SR fibers are likely inputs to the crossed-olivocochlear reflex, a reflex that serves an antimasking role in the detection of sounds in a binaural noise field. If true for humans, the loss of the low-SR system could explain many of the hearing deficits often seen in older individuals; e.g., decreased ability to understand speech in noise, changes in masking level differences, and decreased ability to localize sound sources using binaural cues.
Neurons in the cat pretectum that project to the dorsal lateral geniculate nucleus are activated during saccades
Authors: Schmidt M.
Published: December 2017

1. Neurons in the pretectal nuclear complex that project to the ipsilateral dorsal lateral geniculate nucleus (LGNd) were identified by antidromic activation after electrical LGNd stimulation in awake cats, and their response properties were characterized to retinal image shifts elicited either by external visual stimulus movements or during spontaneous saccadic eye movements on a stationary visual stimulus, and to saccades in darkness. Eye position was monitored with the use of a scleral search coil and care was taken to assure stability of the eyes during presentation of moving visual stimuli. 2. Of a total sample of 134 cells recorded, 27 neurons were antidromically activated by electrical LGNd stimulation. In addition, responses from neurons that were not activated from the LGNd were also analyzed, including 19 “retinal slip” cells, which selectively respond to slow horizontal stimulus movements, and 21 “jerk” cells, which are specifically activated by rapid stimulus shifts. All recorded neurons were located in the nucleus of the optic tract and in the posterior pretectal nucleus. 3. In the light, neurons identified as projecting to the LGNd responded maximally to saccadic eye movements and to externally generated sudden shifts of large visual stimuli. Slow stimulus drifts did not activate these neurons. Response latencies were shorter and peak activities were increased during saccades compared with pure visual stimulation. No systematic correlation between response latency, response duration, or the number of spikes in the response and saccade direction, saccade amplitude, or saccade duration was found. Saccades and rapid stimulus shifts in the light also activated jerk cells but not retinal slip cells. 4. All 27 antidromically activated neurons also responded to spontaneous saccadic eye movements in complete darkness. Responses to saccades in the dark, however, had longer response latencies and lower peak activities than responses to saccades in light. As in the light, response parameters in darkness seemed not to code specific saccade parameters. Cells that were not activated from LGNd were found to be unresponsive to saccades in the dark. 5. According to their specific activation by saccades in darkness, LGNd-projecting pretectal neurons are termed “saccade neurons” to distinguish them from other pretectal cell populations, in particular from jerk neurons, which show similar response properties in light. 6. The saccade-related activation of pretectal saccade neurons may be used to modulate visual responses of LGNd relay cells following saccadic eye movements. Because the pretectogeniculate projection in cat most likely is GABAergic and terminates on inhibitory LGNd interneurons, its activation may lead to a saccade-locked disinhibition of relay cells. This input could counter the strong inhibition induced in the LGNd after shifts of gaze direction and lead to a resetting of LGNd cell activity.
Coordinating two degrees of freedom during human arm movement: load and speed invariance of relative joint torques
Authors: Gottlieb G. L. , Song Q. , Hong D. A. , Corcos D. M.
Published: December 2017

1. Eight subjects performed three series of pointing tasks with the unconstrained arm. Series one and two required subjects to move between two fixed targets as quickly as possible with different weights attached to the wrist. By specifying initial and final positions of the finger tip, the first series was performed by flexion of both shoulder and elbow and the second by shoulder flexion and elbow extension. The third series required flexion at both joints, and subjects were instructed to vary movement speed. We examined how variations in load or intended speed were associated with changes in the amount and timing of the electromyographic (EMG) activity and the net muscle torque production. 2. EMG and torque patterns at the individual joints varied with load and speed according to most of the same rules we have described for single-joint movements. 1) Movements were produced by biphasic torque pulses and biphasic or triphasic EMG bursts at both joints. 2) The accelerating impulse was proportional to the load when the subject moved “as fast and accurately as possible” or to speed if that was intentionally varied. 3) The area of the EMG bursts of agonist muscles varied with the impulse. 4) The rates of rise of the net muscle torques and of the EMG bursts were proportional to intended speed and insensitive to inertial load. 5) The areas of the antagonist muscle EMG bursts were proportional to intended movement speed but showed less dependence on load, which is unlike what is observed during single-joint movements. 3. Comparisons across joints showed that the impulse produced at the shoulder was proportional to that produced at the elbow as both varied together with load and speed. The torques at the two joints varied in close synchrony, achieving maxima and going through zero almost simultaneously. 4. We hypothesize that “coordination” of the elbow and shoulder is by the planning and generation of synchronized, biphasic muscle torque pulses that remain in near linear proportionality to each other throughout most of the movement. This linear synergy produces movements with the commonly observed kinematic properties and that are preserved over changes in speed and load.
Ca2+ signaling pathways linked to glutamate receptor activation in the somatic and dendritic regions of cultured cerebellar purkinje neurons
Authors: Gruol D. L. , Netzeband J. G. , Parsons K. L.
Published: December 2017

1. Ca2+ signaling elicited by ionotropic alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate (iGluR) and metabotropic (mGluR) glutamate receptor agonists was studied in the somatic and dendritic regions of cultured cerebellar Purkinje neurons using microscopic video imaging and the Ca2+ sensitive dye fura-2. 2. iGluR and mGluR agonists and K+ depolarization applied by brief micropressure pulses evoked Ca2+ signals in both the somatic and dendritic regions of all Purkinje neurons studied. The Ca2+ signals were generated simultaneously in both cellular regions. The Ca+ signals to these stimulants were similar in general form, consisting of an initial peak and slow recovery phase, but differed in details of amplitude, time course, and complexity. 3. Removal of extracellular Ca2+ abolished the Ca2+ signal to the iGluR agonist AMPA, indicating that Ca2+ influx was essential to the generation of Ca2+ signals by iGluR agonists. The Ca2+ channel blocker lanthanum almost completely eliminated the Ca2+ signals to AMPA, indicating that Ca2+ influx through voltage-sensitive Ca2+ channels was the main pathway for Ca2+ influx. Omega-agatoxin IVA, a P-type Ca2+ channel blocker, significantly reduced the Ca2+ signals to AMPA suggesting that Ca2+ influx was predominately through P-type Ca2+ channels. 4. Pharmacological manipulation of intracellular Ca2+ stores significantly reduced the Ca2+ signals to AMPA, indicating that release of Ca2+ from intracellular Ca2+ stores also plays a prominent role in the generation of the Ca2+ signals to iGluR agonists. These manipulations included blocking Ca2+ release from intracellular stores with dantrolene, an antagonist at the ryanodine receptor that controls Ca2+ release from one pool of intracellular Ca2+ stores, and depletion of intracellular Ca2+ stores with caffeine or ryanodine. 5. Ca2+ influx through voltage-sensitive Ca2+ channels did not appear to be involved in the Ca2+ signals to mGluR activation, because neither lanthanum nor omega-agatoxin IVA altered Ca2+ signals to mGluR agonists. Manipulation of intracellular stores with Ca(2+)-ATPase inhibitors and dantrolene significantly reduced the Ca2+ signal to mGluR agonists, indicating that Ca2+ signals were derived from both the inositol trisphosphate (IP3) and the ryanodine receptor-controlled intracellular Ca2+ stores. 6. Ca2+ signals to the iGluR agonist AMPA correlated temporally with the prolonged, multiphasic membrane responses elicited by similar agonist application in parallel electrophysiological studies. Pharmacological manipulation of Ca2+ influx and release of Ca2+ from intracellular stores significantly influenced components of the membrane response to AMPA, indicating a potential modulator or mediator role for Ca2+ in the membrane response to iGluR activation.
Spike train encoding by regular-spiking cells of the visual cortex
Authors: Carandini M. , Mechler F. , Leonard C. S. , Movshon J. A.
Published: December 2017

1. To study the encoding of input currents into output spike trains by regular-spiking cells, we recorded intracellularly from slices of the guinea pig visual cortex while injecting step, sinusoidal, and broadband noise currents. 2. When measured with sinusoidal currents, the frequency tuning of the spike responses was markedly band-pass. The preferred frequency was between 8 and 30 Hz, and grew with stimulus amplitude and mean intensity. 3. Stimulation with broadband noise currents dramatically enhanced the gain of the spike responses at low and high frequencies, yielding an essentially flat frequency tuning between 0.1 and 130 Hz. 4. The averaged spike responses to sinusoidal currents exhibited two nonlinearities: rectification and spike synchronization. By contrast, no nonlinearity was evident in the averaged responses to broadband noise stimuli. 5. These properties of the spike responses were not present in the membrane potential responses. The latter were roughly linear, and their frequency tuning was low-pass and well fit by a single-compartment passive model of the cell membrane composed of a resistance and a capacitance in parallel (RC circuit). 6. To account for the spike responses, we used a “sandwich model” consisting of a low-pass linear filter (the RC circuit), a rectification nonlinearity, and a high-pass linear filter. The model is described by six parameters and predicts analog firing rates rather than discrete spikes. It provided satisfactory fits to the firing rate responses to steps, sinusoids, and broadband noise currents. 7. The properties of spike encoding are consistent with temporal nonlinearities of the visual responses in V1, such as the dependence of response frequency tuning and latency on stimulus contrast and bandwidth. We speculate that one of the roles of the high-frequency membrane potential fluctuations observed in vivo could be to amplify and linearize the responses to lower, stimulus-related frequencies.
Selective expression of transient outward currents in different types of acutely isolated hippocampal interneurons
Authors: Fan S. H. , Wong R. K.
Published: December 2017

1. Voltage-dependent outward currents in CA1 interneurons were studied with the use of whole cell voltage-clamp techniques. Tissue slices containing strata lacunosum-moleculare and radiatum (L-M-R regions) of the hippocampal CA1 region were prepared. Neurons were then isolated from these tissue slices with the use of an acute dissociation procedure. The morphologies of the isolated neurons were distinct from those of pyramidal cells and correlated with those of interneurons identified in the L-M-R regions after immunohistochemical stainings. 2. Total outward currents were elicited from the isolated cells by depolarization steps applied after a 300-ms hyperpolarization prepulse to 100 mV from a holding potential of 50 mV. Delayed outward currents were obtained by intercalating a 120-ms step at 55 mV between the hyperpolarizing prepulse and the depolarization. The intercalating step served to inactivate transient outward currents. Transient outward current were isolated by subtracting the delayed outward currents from the total outward currents. 3. Interneurons were subgrouped on the basis of their ability to produce transient outward current in response to the above protocol. 4. The two groups of interneurons possessed distinct morphological features. Cells producing transient outward currents had polygonal-shaped somata with thick primary processes that gave rise to smaller secondary processes at a short distance from the soma. Interneurons without activatable transient outward currents had somata that were not polygonal and they had more slender primary dendritic processes. 5. These results suggest that interneurons in the L-M-R regions can be divided into two groups on the basis of the presence or absence of voltage-dependent transient outward currents. The two groups of cells differentiated on this basis also have distinguishable morphological traits. The difference in the properties of the outward current may be a factor contributing to the variation in the firing pattern of recorded interneurons reported in previous studies.
Nerve growth factor NT-5 induce increased thermal sensitivity of cutaneous nociceptors in vitro
Authors: Rueff A. , Mendell L. M.
Published: December 2017

1. Perfusion of the receptive field (RF) of C- or A delta-fiber nociceptors with nerve growth factor (NGF) in an in vitro preparation of the rat saphenous nerve with functionally attached skin induced a significant decrease in heat threshold without changing mechanical or cold sensitivity. 2. NGF-induced thermal sensitization was absent after saline perfusion and in skin taken from mast-cell depleted animals, hence confirming a role for mast cells in NGF-induced thermal hyperalgesia. 3. Neurotrophin-5 (NT-5) also induced a small but significant reduction in heat threshold without affecting mechanical sensitivity. It is speculated that NT-5 exerts its action either directly on the trkA receptor, as with NGF or alternatively through trkB receptors located on sympathetic efferents or on small diameter afferents.
Cooling-specific spinothalamic neurons in the monkey
Authors: Dostrovsky J. O. , Craig A. D.
Published: December 2017

1. Little is known concerning the processing of innocuous thermoreceptive information in the CNS of the monkey. The aim of the present study was to confirm the prediction, based on recent studies in cat and monkey, that there must be a prominent spinothalamic (STT) projection of cooling-specific spinal cord lamina I neurons to the posterior part of the ventral medial nucleus (VMpo) of the monkey thalamus. 2. Experiments were performed on four cynomolgus monkeys anesthetized with pentobarbital sodium. A detailed mapping of somatosensory thalamus was performed in each animal, and VMpo was identified by recordings from clusters of thermoreceptive-specific and nociceptive-specific (NS) neurons. Stimulating electrodes were then implanted in VMpo. Tungsten microelectrodes were used to record the responses of neurons in the superficial dorsal horn of the lumbosacral spinal cord. 3. Many spontaneously active lamina I neurons were found that were inhibited by radiant warming and that responded to innocuous cooling of the hindpaw. These cooling-specific (COLD) neurons were excited by small temperature drops below skin temperature and increased their discharge with decreasing skin temperature. They were not excited by thermally neutral mechanical stimuli applied to the receptive fields. In passing, we also characterized with natural stimulation a few NS neurons reponsive to pinch and/ or noxious heat, multimodal (HPC) neurons responsive to noxious heat, pinch, and cold stimuli, and wide-dynamic-range neurons responsive to both innocuous and noxius cutaneous stimuli that were encountered in lamina I. 4. Twenty lamina I COLD cells were identified as STT neurons by antidromic activation from the contralateral VMpo. The mean conduction latency for these units was 26.1 ms, which corresponds to a mean conduction velocity of approximately 8.0 m/s. They were not antidromically activated from an electrode in the region of the ventral posterior nucleus in the thalamus. In addition, we antidromically activated from VMpo four NS units and three HPC cells. 5. These findings demonstrate for the first time the existence of a prominent direct projection of specific COLD lamina I STT cells to thalamus in the monkey. This is consistent with clinical inferences in humans and with prior results in cats. This result confirms that the dense lamina I STT projection to VMpo demonstrated in anatomic studies includes COLD cells, and it supports the role of VMpo as a thalamic relay nucleus for pain- and temperature-related information.
Adrenoreceptor subtype mediating sympathetic-sensory coupling in injured sensory neurons
Authors: Chen Y. , Michaelis M. , Janig W. , Devor M.
Published: December 2017

1. Teased axon recordings were made from 167 spontaneously active A beta- and A delta-afferents that ended in sciatic nerve end neuromas of 6-12 days standing. When challenged with a standard bolus of systemically applied adrenaline, 100 (60%) responded, either with an increase in baseline firing frequency (excitation, 96/100) or with a decrease (suppression, 4/100). 2. Experiments using receptor type-selective antagonists indicated that the adreno-sensitivity was mediated by alpha 2 adrenoreceptors in 65% of the afferents sampled, by alpha 1 adrenoreceptors in 13%, and about equally by alpha 1 and alpha 2 adrenoreceptors in approximately 10%. In the remaining 13%, neither type of antagonist blocked adrenaline-evoked excitation, at least not at the doses used. Both excitatory and suppressive responses were primarily sensitive to alpha 2 antagonists. 3. Experiments using receptor type-selective agonists substantiated the conclusion that sympathetic-sensory coupling at sites of nerve injury is mediated primarily by alpha 2 adrenoreceptors. 4. Recordings were also made from 14 afferent neurons with spontaneous ectopic discharge originating in dorsal root ganglia (DRGs) L4 and L5. The rats had undergone transection of the ipsilateral sciatic nerve 8–93 days previously. All neurons responded to systemic adrenaline and/or trains of activity evoked in postganglionic sympathetic efferents with either excitation or suppression. As in the neuroma endings, responses in the large majority of cases were blocked by alpha 2-selective, but not by alpha 1-selective adrenoreceptor antagonists. 5. The results indicate that sympathetic-sensory coupling, both at nerve injury sites and in axotomized DRG neurons, is mediated primarily by alpha 2 adrenoreceptors. In a minority of afferent neurons, however, it appears to be mediated by alpha 1 adreno-receptors or by both alpha 1 and alpha 2 adrenoreceptors. These functional results are consistent with receptor-type expression profiles from studies based on in situ hybridization and immunocytochemistry.
Muscarine receptor activation in the substantia gelatinosa of the spinal trigeminal nucleus of the guinea pig
Authors: Travagli R. A.
Published: December 2017

1. Intracellular recordings were made from slices of guinea pig spinal trigeminal nucleus pars caudalis (SG). 2. Muscarine [0.3–30 microM; half maximally effective concentration (EC50) = 2.9 microM] hyperpolarized 61% of SG neurons. The effect was mimicked by carbachol (0.3–30 microM; EC50 = 3.9 microM) and antagonized by pirenzepine (1 microM). Thirty-four percent of the neurons were depolarized by muscarine and carbachol (1–30 microM: EC50 = 5.7 microM), and the effect was antagonized by pirenzepine (100 nM). 3. In approximately 80% of recordings, muscarine (10–30 microM) evoked repetitive spontaneous inhibitory postsynaptic potentials (IPSPs) that were sensitive to bicuculline (10 microM). 4. Muscarine (1–30 microM; EC50 = 3 microM) decreased the amplitude of the majority of evoked excitatory postsynaptic potentials (EPSPs), and the effect was mimicked by carbachol and antagonized by pirenzepine (100 nM). 5. These results indicate that there are at least three mechanisms by which muscarine inhibits SG neurons: 1) hyperpolarization through activation of non-M1 receptors; 2) activation of gamma-amino-butyric acid-containing interneurons that mediate IPSPs in a subset of neurons; and 3) a decrease in evoked EPSP amplitude. Muscarine can also activate SG neurons via interaction with an M1-type receptor.
Maturation in properties of motoneurons and their segmental input in the neonatal rat
Authors: Seebach B. S. , Mendell L. M.
Published: December 2017

1. The isolated neonatal rat spinal chord preparation was used to investigate the development of segmental afferent input to lumbar motoneourons during the first nine postnatal days. Motoneurons, identified with the use of antidromic stimulation of the ventral roots, were characterized electrophysiologically, and their synaptic input in response to stimulation of the homologous dorsal root was studied. 2. Motoneurons in postnatal day (P) 1–3 preparations exhibited lower rheobase and lower input conductance than those impaled in spinal cords taken from animals at P7-9. This finding is consistent with the increase in motoneuron size known to occur during this time. 3. Monosynaptic excitatory postsynaptic potentials (EPSPs) evoked at low-frequency (0.1-Hz) stimulation in high-Ca2+ saline exhibited no change in mean amplitude between P1-3 and P7-9 despite an increase in input conductance of the motoneurons, suggesting that some aspect of these synapses underwent a compensatory change. Polysynaptic EPSPs were smaller in the older animals. 4. When bursts of stimuli were delivered at higher frequencies ranging from 10 to 167 Hz, the EPSPs exhibited substantial depression. The depression of monosynaptic EPSPs was significantly less at P7-9 than at P1-3. Changing the bathing solution from a high-Ca2+ saline to a low-Ca2+/high-Mg2+ saline reduced the amplitude of the monosynaptic EPSP and made it less susceptible to depression during high-frequency stimulation. Facilitation of the evoked response, which has been observed in the adult rat, was never seen under any of these conditions. 5. Although synapses on high-rheobase motoneurons exhibited less depression than those on low-rheobase motoneurons, as anticipated from previous results in adults, the EPSPs at synapses on high-rheobase motoneurons tended to be larger in amplitude, not smaller as expected. This suggests that the specialization among synapses on motoneurons that exists in adults has not yet developed by P7-9. Instead, EPSP amplitude may be greater in motoneurons that have been growing rapidly, such as the high-rheobase motoneurons found during these stages of development. 6. Evidence is presented that the growing diversity shown in modulation behavior at the Ia afferent motoneuron synapse during the first postnatal week is determined primarily by motoneuron characteristics. It is speculated that as motoneurons grow during the immediate postnatal period, the presynaptic terminal regions of axons terminating on them become specialized to render the synapse less susceptible to depression. This specialization may be myelination of the afferent terminals or may perhaps be related to the transmitter release process itself. The adult distribution of depression develops later, presumably as the components of the monosynaptic reflex mature.
Differential responses of Aplysia siphon motor neurons and interneurons to tail and mantle stimuli: implications for behavioral response specificity
Authors: Fang X. , Clark G. A.
Published: December 2017

1. Tail shock and mantle shock elicit different forms of siphon responses in Aplysia (flaring and backward bending vs. constriction and forward bending, respectively). Moreover, training with these two unconditioned stimuli (USs) in US-alone or classical conditioning paradigms differentially modifies the direction of the response to a siphon tap subsequently presented. As a first step toward addressing neural mechanisms underlying this response specificity, we systematically mapped the central siphon withdrawal circuit to determine which motor neurons and interneurons are differentially engaged by, and potentially modified by, tail and mantle USs. We utilized semi-intact preparations consisting of the intact mantle organs (including the gill and siphon), the tail, and the abdominal and circumesophageal ganglia. USs were delivered either cutaneously through silver wires implanted in the tail and mantle or via suction electrodes to the tail and branchial nerves. 2. We found that one class of central siphon motor neurons, the LFSB cells, was preferentially activated by tail USs, whereas other siphon motor neurons, the LBs cells and RDs cells, were preferentially activated by mantle USs. These motor neurons thus appear to be the final common path for the differential siphon movements to these USs. In addition, because activation of these cells can elicit neuromuscular facilitation and thereby enhance siphon movements, this differential activation may contribute to behavioral response specificity by imposing a specific response bias. 3. L29 interneurons, which both mediate and modulate the siphon withdrawal response, responded preferentially and exhibited synaptic facilitation selectively in response to tail shock USs. In contrast, L34 and the interneuron II network did not show differential activation. Facilitation at L29-LFSB connections following training with tail shock may contribute to tail-directed siphon responses to siphon tap and may thus be an additional mechanism contributing to behavioral response specificity. Possibly, facilitation at other L29 connections could also enhance its modulatory capabilities. 4. The generation of specific response topographies thus appears to involve the coordinate regulation of diverse neuronal elements and multiple mechanisms, which may contribute to different aspects of learning.
Control of transmission in muscle group IA afferents during fictive locomotion in the cat
Authors: Gossard J. P.
Published: December 2017

1. Primary afferent depolarization (PAD) can be evoked by sensory volleys, supraspinal commands, or the activity of spinal locomotor networks (locomotor-related PAD). In this study we investigated the effect of locomotor-related PAD and of sensory-evoked PAD on the monosynaptic transmission between the group IA muscle afferents and motoneurons in the lumbosacral spinal cord. 2. Six pairs of group IA afferents and motoneurons [4 tibialis anterior (TA), 1 medial gastrocnemius (MG), 1 lateral gastrocnemius-soleus (LGS)] were successfully recorded intracellularly during spontaneous fictive locomotion in the decerebrate cat. The membrane potentials of TA axons and motoneurons were maximally depolarized during the flexor phase of the locomotor cycle. In MG and LGS pairs, the maximum depolarization in IA axons occurred during the flexor phase and, in motoneurons, during the extensor phase. There were no antidromic discharges in the recorded axons. The effects of locomotor-related PAD on IA transmission were evaluated by comparing the unitary excitatory postsynaptic potentials (EPSPs) in the motoneuron evoked by the spontaneous orthodromic firing of the group IA axon during the flexor and extensor phases, respectively. In TA pairs, the maximum amplitude of unitary EPSPs occurred during the flexor phase when the motoneuron and the axon were maximally depolarized. In the MG and LGS pairs, the maximal amplitude of unitary EPSPs occurred during the extensor phase when the motoneuron was maximally depolarized and when the axon was the least depolarized. Overall, the amplitude of unitary EPSPs was clearly modulated during the fictive step cycle and always reached a maximum during the depolarized phase of the motoneuron, whether the group IA axon was maximally depolarized or not during that phase. 3. The effect of sensory-evoked PAD on synaptic transmission was also studied in nonlocomoting preparations. One TA pair was successfully recorded and PADs were evoked by the stimulation of a peripheral nerve. The amplitude of unitary EPSPs in the motoneuron was greatly depressed during the PADs. This result is a direct demonstration of the presynaptic inhibition associated with the sensory-evoked PAD in the monosynaptic reflex pathway of the cat. 4. We conclude from these results that the locomotor-related PAD did not contribute significantly to the modulation of transmission in the monosynaptic reflex pathway of the cat during fictive locomotion. On the other hand, the results confirmed that PAD evoked by sensory input decreases group IA afferent transmission efficiently most probably by presynaptic inhibition. The results suggest therefore that, during real locomotion, sensory feedback induced by the moving limbs or perturbations will evoke an important presynaptic inhibition of the release from group IA primary afferent terminals.
Generation of high-frequency oscillations in local circuits of rat somatosensory cortex cultures
Authors: Plenz D. , Kitai S. T.
Published: December 2017

1. Rhythmic cortical activity was investigated with intracellular recordings in cortex-striatum-mesencephalon organotypic cultures grown for 42 +/- 3 (SE) days in vitro. 2. Electrical stimulation of supragranular layers induced a self-sustained high-frequency oscillation (HFO) in pyramidal neurons and interneurons. 3. The HFO started 197 +/- 39 ms after stimulation and had a mean duration of 1.0 +/- 0.2 s and an initial frequency of 38 +/- 2 Hz. A decrease in frequency at a rate of 11.5 +/- 2.7 Hz/s started on average 547 +/- 109 ms after the onset of the HFO. 4. During the HFO, local interneurons and pyramidal neurons synchronized their activities. The synaptic origin of the HFO was confirmed by its reversal potential at -57 +/- 4 mV. 5. These results suggest that a self-maintained HFO can be induced in local cortical circuits by excitation of supragranular layers. This HFO would facilitate synchronization between distant cortical and thalamic regions.
Brain-derived neurotrophic factor blocks long-term depression in rat visual cortex
Authors: Akaneya Y. , Tsumoto T. , Hatanaka H.
Published: December 2017

1. Brain-derived neurotrophic factor (BDNF) has been reported to play a role in long-term potentiation (LTP) in hippocampus, but whether it is involved also in long-term depression (LTD) is not yet known. In this study, we tested whether BDNF and its gene family, nerve growth factor (NGF), have any effect on synaptic transmission and LTD in visual cortical slices of young rats. 2. An application of BDNF at the concentration of 20 ng/ml did not significantly change layer II/III field responses evoked by layer IV stimulation at 0.1 Hz, although at 200 ng/ml it enhanced responses. BDNF at 20 ng/ml prevented LTD of field responses from being induced by low-frequency stimulation (1 Hz for 15 min) of layer IV. NGF did not have such effects in the same concentration range as that of BDNF. 3. The action of BDNF was antagonized by K252a, an inhibitor of receptor tyrosine kinases. When K252a alone was applied to slices, LTD of stronger magnitude than in control slices was induced by low-frequency stimulation. 4. These results suggest that endogeneous BDNF may prevent synapses from being depressed by low-frequency inputs in the developing visual cortex.
Cholinergic Activation of Startle Motoneurons by a Pair of Cerebral Interneurons in the Pteropod MolluskClione limacina
Authors: Norekian Tigran P. , Satterlie Richard A.
Published: December 2017

Norekian, Tigran P. and Richard A. Satterlie. Cholinergic activation of startle motoneurons by a pair of cerebral interneurons in the pteropod mollusk Clione limacina. J. Neurophysiol. 77: 281–288, 1997. The holoplanktonic pteropod mollusk Clione limacina exhibits an active escape behavior that is characterized by fast swimming away from the source of potentially harmful stimuli. The initial phase of escape behavior is a startle response that is controlled by pedal motoneurons whose activity is independent of the normal swim pattern generator. In this study, a pair of cerebral interneurons is described that produces strong activation of the d-phase startle motoneurons, which control dorsal flexion of the wings. These interneurons were designated cerebral startle (Cr-St) interneurons. Each Cr-St neuron has a small cell body on the dorsal surface of the cerebral ganglia and one large axon that runs into the ipsilateral cerebral-pedal connective and the neuropile of the ipsilateral pedal ganglion. Each spike in a Cr-St neuron produces a fast, high-amplitude (up to 50 mV) excitatory postsynaptic potential (EPSP) in the d-phase startle motoneurons. This 1:1 ratio of spikes to EPSPs and the stable short synaptic latencies (2 ms) persist in high-Mg2+, high-Ca2+seawater, suggesting monosynaptic connections. Synaptic transmission between Cr-St neurons and startle motoneurons exhibits a very slow synaptic depression, because a number of spikes in Cr-St neurons is required to achieve a noticeable decrease in EPSP amplitude. Synaptic transmission between Cr-St interneurons and startle motoneurons appears to be cholinergic. In startle neurons, 20 μM atropine and 50 μM d-tubocurarine reversibly block EPSPs produced by spike activity in Cr-St interneurons. Hexamethonium only partially blocks EPSPs in startle neurons, and much higher concentrations are required. Exogenous acetylcholine (1 μM) produces a dramatic depolarization of startle motoneurons in high-Mg2+seawater, and this depolarization is reversibly blocked by atropine. Nicotine also has a depolarizing effect on startle motoneurons, although higher concentrations are required. Cr-St interneurons and startle motoneurons are also electrically coupled; however, the coupling is weak. Stimuli that are known to initiate escape responses in intact animals, such as tactile stimulation of the tail or wings, produce excitatory inputs to Cr-St interneurons. In addition, tactile stimulation of the lips and buccal cones, which is known to trigger prey capture reactions in Clione, also produces excitatory inputs to Cr-St interneurons and startle motoneurons, suggesting involvement of the startle neuronal system in prey capture behavior of Clione.
Dopaminergic Modulation of Spinal Neurons and Synaptic Potentials in the Lamprey Spinal Cord
Authors: Kemnitz Christopher P.
Published: December 2017

Kemnitz, Christopher P. Dopamineric modulation of spinal neurons and synaptic potentials in the lamprey spinal cord. J. Neurophysiol. 77: 289–298, 1997. It has been shown previously that dopamine-immunoreactive cells and processes are present in the lamprey spinal cord and that dopamine modulates the cycle period of fictive swimming. The present study was undertaken to further characterize the effects of dopamine on the cellular properties of lamprey spinal neurons and on inhibitory and excitatory postsynaptic potentials to determine how dopaminergic modulation may affect the central pattern generator for locomotion. Dopamine reduced the late afterhyperpolarization (late AHP) following the action potential of motoneurons, and in three types of sensory neurons: dorsal cells, edge cells, and giant interneurons. The late AHP was not reduced in lateral interneurons or CC interneurons, both of which are part of the central motor pattern generating neural network. The reduction of the late AHP in motoneurons, edge cells, and giant interneurons resulted in an increase in firing frequency in response to depolarizing current injection. In the six cell classes examined, no changes were observed in the resting membrane potential, input resistance, rheobase, spike amplitude, or spike duration after application of dopamine. The durations of action potentials broadened by application of tetraethylammonium in motoneurons and of calcium action potentials in dorsal cells and giant interneurons were decreased after bath application of 10 μM dopamine. The durations of tetrodotoxin-resistant, N-methyl-d-aspartate-induced membrane potential oscillations in lamprey spinal motoneurons were increased after bath application of 1–100 μM dopamine, due perhaps to reduced calcium entry and thus reduced Ca2+-dependent K+current responsible for the repolarization of the membrane potential during each oscillation. Polysynaptic inhibitory postsynaptic potentials (IPSPs) elicited in lamprey spinal motoneurons by stimulation of the contralateral half of the spinal cord were reduced by bath application of 10 μM dopamine. Polysynaptic excitatory postsynaptic potentials were not reduced by dopamine. Monosynaptic IPSPs in motoneurons elicited by stimulation of single contralateral inhibitory CC interneurons and single ipsilateral axons were reduced by bath application of dopamine (10 μM). Monosynaptic IPSPs in CC interneurons elicited by stimulation of ipsilateral lateral interneurons, however, showed no change after application of dopamine. The lack of dopaminergic effect on the late AHP of the locomotor network neurons, lateral interneurons and CC interneurons, and the selective reduction of IPSPs from CC interneurons suggest that synaptic modulation may play an important role in dopaminergic modulation of cycle period during fictive swimming in the lamprey.
Trapping Channel Block of NMDA-Activated Responses By Amantadine and Memantine
Authors: Blanpied Thomas A. , Boeckman Faye A. , Aizenman Elias , Johnson Jon W.
Published: December 2017

Blanpied, Thomas A., Faye Boeckman, Elias Aizenman, and Jon W. Johnson. Trapping channel block of NMDA-activated responses by amantadine and memantine. J. Neurophysiol. 77: 309–323, 1997. We investigated the mechanisms by which the antiparkinsonian and neuroprotective agents amantadine and memantine inhibit responses to N-methyl-d-aspartic acid (NMDA). Whole cell recordings were performed using cultured rat cortical neurons or Chinese hamster ovary (CHO) cells expressing NMDA receptors. Both amantadine and memantine blocked NMDA-activated channels by binding to a site at which they could be trapped after channel closure and agonist unbinding. For neuronal receptors, the IC50s of amantadine and memantine at −67 mV were 39 and 1.4 μM, respectively. When memantine and agonists were washed off after steady-state block, one-sixth of the blocked channels released rather than trapped the blocker; memantine exhibited “partial trapping.” Thus memantine appears to have a lesser tendency to be trapped than do phencyclidine or (5R,10S)-(+)-5m e t h y l - 1 0 , 1 1 - d i h y d r o - 5 H - d i b e n z o [ 1 , d ] c y c l i h e p t e n - 5 , 1 0 - i m i n e(MK-801). We next investigated mechanisms that might underlie partial trapping. Memantine blocked and could be trapped by recombinant NMDA receptors composed of NR1 and either NR2A or NR2B subunits. In these receptors, as in the native receptors, the drug was released from one-sixth of blocked channels rather than being trapped in all of them. The partial trapping we observed therefore was not due to variability in the action of memantine on a heterogeneous population of NMDA receptors in cultured cortical neurons. Amantadine and memantine each noncompetitively inhibited NMDA-activated responses by binding at a second site with roughly 100-fold lower affinity, but this form of inhibition had little effect on the extent to which memantine was trapped. A simple kinetic model of blocker action was used to demonstrate that partial trapping can result if the presence of memantine in the channel affects the gating transitions or agonist affinity of the NMDA receptor. Partial trapping guarantees that during synaptic communication in the presence of blocker, some channels will release the blocker between synaptic responses. The extent to which amantadine and memantine become trapped after channel block thus may influence their therapeutic effects and their modulation of NMDA-receptor-mediated excitatory postsynaptic potentials.