Bursts Of High-frequency Activity Research Articles

Pulse and Meter as Neural Resonance

The experience of musical rhythm is a remarkable psychophysical phenomenon, in part because the perception of periodicities, namely pulse and meter, arise from stimuli that are not periodic. One possible function of such a transformation is to enable synchronization between individuals through perception of a common abstract temporal structure (e.g., during music performance). Thus, understanding the brain processes that underlie rhythm perception is fundamental to explaining musical behavior. Here, we propose that neural resonance provides an excellent account of many aspects of human rhythm perception. Our framework is consistent with recent brain-imaging studies showing neural correlates of rhythm perception in high-frequency oscillatory activity, and leads to the hypothesis that perception of pulse and meter result from rhythmic bursts of high-frequency neural activity in response to musical rhythms. High-frequency bursts of activity may enable communication between neural areas, such as auditory and motor cortices, during rhythm perception and production.

A NMDA receptor glycine site partial agonist, GLYX-13, simultaneously enhances LTP and reduces LTD at Schaffer collateral–CA1 synapses in hippocampus

N-methyl- d-aspartate glutamate receptors (NMDARs) are a key route for Ca 2+ influx into neurons important to both activity-dependent synaptic plasticity and, when uncontrolled, triggering events that cause neuronal degeneration and death. Among regulatory binding sites on the NMDAR complex is a glycine binding site, distinct from the glutamate binding site, which must be co-activated for NMDAR channel opening. We developed a novel glycine site partial agonist, GLYX-13, which is both nootropic and neuroprotective in vivo. Here, we assessed the effects of GLYX-13 on long-term synaptic plasticity and NMDAR transmission at Schaffer collateral–CA1 synapses in hippocampal slices in vitro. GLYX-13 simultaneously enhanced the magnitude of long-term potentiation (LTP) of synaptic transmission, while reducing long-term depression (LTD). GLYX-13 reduced NMDA receptor-mediated synaptic currents in CA1 pyramidal neurons evoked by low frequency Schaffer collateral stimulation, but enhanced NMDAR currents during high frequency bursts of activity, and these actions were occluded by a saturating concentration of the glycine site agonist d-serine. Direct two-photon imaging of Schaffer collateral burst-evoked increases in [Ca 2+] in individual dendritic spines revealed that GLYX-13 selectively enhanced burst-induced NMDAR-dependent spine Ca 2+ influx. Examining the rate of MK-801 block of synaptic versus extrasynaptic NMDAR-gated channels revealed that GLYX-13 selectively enhanced activation of burst-driven extrasynaptic NMDARs, with an action that was blocked by the NR2B-selective NMDAR antagonist ifenprodil. Our data suggest that GLYX-13 may have unique therapeutic potential as a learning and memory enhancer because of its ability to simultaneously enhance LTP and suppress LTD.

Discharge Variability of Motor Units in an Intrinsic Muscle of Transplanted Hand

The study analyzed the discharge characteristics of the motor units in an intrinsic muscle of a transplanted hand. Multichannel electromyographic (EMG) recordings were obtained in 11 experimental sessions over 16 mo starting from day 205 after a hand was transplanted in a 35-yr-old man who had lost his right hand 22 yr earlier. The action potentials discharged by single motor units were identified from the surface EMG signals of the abductor digiti minimi muscle in the transplanted hand as the individual performed 60-s maximal and linearly increasing (ramp) contractions. Discharge rate decreased from 27.1 +/- 8.4 pulses per second (pps) at the start of the maximal contractions to 17.2 +/- 2.9 pps at the end (P < 0.001) and increased from 17.4 +/- 4.3 to 22.1 +/- 5.0 pps during the ramp contractions (P < 0.05). The SD of the interspike interval (ISI) nearly related to the mean ISI with a similar regression slope for the maximal (0.49 +/- 0.09) and ramp contractions (0.43 +/- 0.10). The coefficient of variation for ISI was higher than values in able-bodied persons and did not change during either the maximal (36.8 +/- 10.8%) or the ramp contractions (35.9 +/- 7.4%). High-frequency bursts of activity with <20 ms between two and six action potentials occurred during both maximal and ramp contractions. In conclusion, motor neurons that reinnervated a muscle in a transplanted hand discharged action potentials with a high degree of variability that suggested greater synaptic noise during the voluntary contractions.

Functional Maturation of CA1 Synapses Involves Activity-Dependent Loss of Tonic Kainate Receptor-Mediated Inhibition of Glutamate Release

Early in development, excitatory synapses transmit with low efficacy, one mechanism for which is a low probability of transmitter release (Pr). However, little is known about the developmental mechanisms that control activity-dependent maturation of the presynaptic release. Here, we show that during early development, transmission at CA3-CA1 synapses is regulated by a high-affinity, G protein-dependent kainate receptor (KAR), which is endogenously activated by ambient glutamate. By tonically depressing glutamate release, this mechanism sets the dynamic properties of neonatal inputs to favor transmission during high frequency bursts of activity, typical for developing neuronal networks. In response to induction of LTP, the tonic activation of KAR is rapidly down regulated, causing an increase in Pr and profoundly changing the dynamic properties of transmission. Early development of the glutamatergic connectivity thus involves an activity-dependent loss of presynaptic KAR function producing maturation in the mode of excitatory transmission from CA3 to CA1.

Referred pain induced by injection of capsaicin into the rat gastric artery

Rationale: Referred pain (or secondary hyperalgesia) is an increased response to noxious stimuli distant from the site of injury. This secondary hyperalgesia is thought to reflect hyperactivity of central neurons, including those in the spinal dorsal horn. The hypothesis tested was that injury to the stomach will result in sensitization of dorsal horn neurons and cutaneous secondary hyperalgesia. Results: In Experiment 1, behavioral tests for mechanical (yon Frey filaments) and heat sensitivity of the abdomen were performed before and at varying times after gastric artery capsaicin injection. Assessment of spontaneous behaviors demonstrated that capsacin (0.1, 0.3 or 1.0%, 100~l) injected into the left gastric artery induced motor inhibition or arousal at the time of injection. However, capsaicin did not produce vocalization or other signs of distress. There was a dose-dependent decrease in mechanical thresholds on the abdomen 15 rain after capsaicin injection that remained decreased for 3h. No changes were observed in the mechanical threshold for the ipsilateral hindpaw or the latency to respond to radiant heat for the abdomen or paw. To evaluate for possible systemic distribution of capsaicin, the effects of capsaicin injection on plasma extravasation were examined using Evan's Blue dye. Plasma extravasation was confined to the corpus of the stomach; no dye was visible in the abdominal skin in the area of secondary hyperalgesia or other viscera. In Experiment 2, extracellular recordings were made from dorsal horn neurons sensitive to gastric distention before and after injection of capsaicin (0.1%, 100 ~l). At the time of injection, capsaicin evoked high frequency bursts of activity in neurons that lasted up to 5 min, demonstrating that neurons receive nociceptive information from gastric primary afferent fibers. Spinal neurons sensitive to gastric distension were sensitized by capsaicin. Specifically, there was an increase in background discharges of the cells and also an enhanced responsiveness of the cells to gastric distention (10-80 mmHg) 30 min and 60 rain after capsaicin injection. Conclusions: These results suggest that cutaneous secondary hyperalgesia to mechanical stimulation (but not heat) occurs in the stomach viscorotomes on the abdominal wall in response to gastric neurogenic inflammation. Additionally, dorsal horn neurons responsive to gastric stimulation become hyperactive following injection of capsaicin into the gastric artery, revealing central sensitization. The changes observed after injection of capsaicin into the gastric artery are similar to those observed following capsaicin injection into the skin. The convergence of somatic and visceral primary afferent fibers onto dorsal horn neurons is likely the basis of cutaneous hyperalgesia (i.e., referred pain) associated with gastritis. Supported by NS 19912.

LHRH and GTP-γ-S modify calcium current activation in bullfrog sympathetic neurons

LHRH (chicken II luteinizing hormone-releasing hormone) partially reduces calcium currents and slows the activation kinetics of part of the remaining current in frog sympathetic neurons. The effects of LHRH are mimicked by intracellular dialysis with GTP-γ-S. A strong depolarization can temporarily reverse the effects of LHRH or GTP-γ-S: activation kinetics return to normal, and the amplitude of the current is increased (facilitation). Facilitation develops rapidly (π = 4–6 ms at >+30 mV) and decays more slowly ( t 1 2 = 60 ms at −80 mV). Tail currents in LHRH are smaller and faster than in the control, and these effects are partially reversed by facilitation. These results can be explained by a model in which a fraction of the channels is shifted into a “reluctant” gating mode, where opening requires stronger depolarization. If this mechanism is at the root of presynaptic inhibition, our results predict that inhibition of transmitter release would be overcome during bursts of high frequency activity.

Supraoptic neurons sustain high frequency firing when extracellular Ca 2+ is replaced with other divalent cations in rat brain slices

In slices of hypothalamus, maintained in vitro, the discharge of supraoptic neurons in standard artificial cerebrospinal fluid was compared with that produced when extracellular Ca 2+ was replaced with Mg 2+, Co 2+ or Mn 2+. Interspike interval histograms were constructed for periods before, during and after replacement of extracellular Ca 2+. Of the 31 cells recorded in normal medium, 16 fired slowly and irregularly, 9 were phasic, 3 fired continuously at more than 3 spikes/s and 3 produced short, high frequency bursts of activity that were separated by slow irregular discharge. Interspike interval distributions were broad showing little preference for any one interval and intervals shorter than 30–50 ms were rare. The cell firing rate could be increased by the electrophoretic application of glutamate and under these conditions, the interval distributions became narrower as shorter intervals predominated. However, when cells discharged above 20 spikes/s, the spike amplitude declined rapidly and became indistinguishable from the noise. Replacement of extracellular Ca 2+ with Mg 2+, Co 2+ or Mn 2+ produced reversible changes in interspike interval distribution, although no consistent change in mean firing frequency was observed. Supraoptic neurons were now able to maintain relatively high frequency discharge (15–25 spikes/s) for longer periods; firing either continuously or periodically and interspike intervals became grouped more closely at the shorter end of the normal distribution. However, no very short interspike intervals were recorded. Less than 2% of all recorded intervals were shorter than 30 ms, even in cells exposed to test medium for 1–3 h and excited by application of glutamate. In cells that were transynaptically activated by electrical stimulation of the slice, exposure to test medium blocked stimulus-evoked spike activity. Calcium may be a necessary factor in the mechanism that prevents sustained high frequency discharge in these neurons under normal conditions, but the mechanism that regulates the minimum interspike interval, which is a striking feature of the normal firing of these cells, appears to be less dependent on extracellular Ca 2+.

Neural inhibition of egg-laying in the locust, Locusta migratoria

The role of the oviducal nerves during egg-laying in Locusta migratoria has been examined. Section of the oviducal nerves did not inhibit egg-laying in any observable way. Electrical stimulation of the oviducal nerves resulted in a contraction of the common and lower lateral oviducts which propelled ovulated eggs up towards the ovaries. Recordings from oviducal nerves using chronically implanted electrodes showed that electrical activity was low during actual egg-laying, but high at times when egg-laying was not occurring (i.e. during digging behaviour, or following interruption of egg-laying). During these periods of high activity recurrent bursts of action potentials occurred. Similar patterns of electrical activity were recorded in semi-intact preparations using suction electrodes applied to exposed oviducal nerves of locusts which had been interrupted during the process of egg-laying. High frequency bursts of activity were recorded simultaneously from both left and right oviducal nerves. It is concluded that one function of the oviducal nerves is to inhibit egg-laying at inappropriate times, by inducing contractions of the oviducts which propel eggs back towards the ovaries. These nerves therefore provide a physiological basis for part of the adaptive ovipositional activities of locusts.

Neurophysiological mechanisms involved in grand mal seizures induced by metrazol and megimide

Electro-clinical correlations during Metrazolor Megimide-induced grand mal seizures were studied in a series of fifty-seven cats. It was found that conventional EEG tracings suggest that earliest and maximal seiaure activity occurs in the cerebral cortex or thalamus, but photographs of the animals' behavior failed to show consistent relationships between any aspect of the conventional EEG and the onset of the behavioral convulsion. When the conventional EEG was eliminated by filters which attenuate activity below 1,000 c/sec, high frequency activity could be recorded from cortical and intracerebral structures. These recordings showed good relationships with the animals' behavior. Clinical myoclonic jerking was associated with large amplitude bursts of high frequency activity maximally in the brain-stem reticular formation. A generalized seizure occurred when the high voltage brain-stem reticular discharge became continuous rather than intermittent. The clonic phase of the generalized seizure was characterized by bursts of high frequency activity which gradually decreased in duration and amplitude toward the end of the seizure. In contrast to the conventional EEG, high frequency activity did not cease abruptly and simultaneously in all areas. The paralyzed and unanesthetized preparation showed less intense high frequency seizure activity than the freely moving animal, and the maximum of seizure activity was under these circumstances in the thalamus and cortex rather than the brain-stem. It is concluded that the recording of high frequency discharges adds a valuable dimension to electro-clinical correlations, and that the functional state of the animal may be an important variable in the amount and relative distribution of seizure activity.